El tratamiento con oxígeno hiperbárico activa las células madre

El tratamiento con oxígeno hiperbárico activa las células madre

En la médula ósea de los seres humanos y de los animales existen células madre que son capaces de cambiar su naturaleza para formar parte de muchos órganos y tejidos diferentes. En respuesta a una lesión, estas células se mueven desde la médula ósea a los sitios dañados, donde se transforman en células diferentes que ayudan en el proceso curativo. El movimiento, o movilización, de las células madre puede ser activado por una variedad de estímulos, incluyendo algunos medicamentos y los tratamientos con oxígeno hiperbárico. Si bien los fármacos traen asociados efectos secundarios, los tratamientos con oxígeno hiperbárico conllevan riesgos significativamente más bajos de tales efectos.



"Ésta es la manera clínicamente más segura de aumentar la circulación de células madre, mucho más segura que cualquiera de las opciones farmacéuticas", explica Stephen Thom, Profesor de Medicina de Emergencias en la Escuela de Medicina de la Universidad de Pensilvania y autor principal del estudio. "Este estudio proporciona información sobre los mecanismos fundamentales de la oxigenación hiperbárica y ofrece una nueva opción terapéutica teórica para activar las células madre".



Los investigadores reprodujeron en animales las observaciones hechas en humanos, con el objetivo de identificar los mecanismos que producen los efectos del oxígeno hiperbárico. Encontraron que este oxígeno activa las células madre porque aumenta la síntesis de una molécula denominada óxido nítrico, en la médula ósea. Se piensa que esta síntesis activa las enzimas que permiten la liberación de las células madre.

Existe la esperanza de que los futuros estudios del papel del oxígeno hiperbárico en la activación de las células madre provean una amplia gama de tratamientos para combatir lesiones y enfermedades.

High-dose HBO2 Therapy Extends Survival Window After Cardiopulmonary Arrest, Study Suggests

High-dose HBO2 Therapy Extends Survival Window After Cardiopulmonary Arrest, Study Suggests

ScienceDaily (July 16, 2008) — A ground-breaking study by researchers at the School of Medicine at LSU Health Sciences Center New Orleans published in the August 2008 issue of Resuscitation has major implications for the #1 cause of death of Americans -- sudden cardiac arrest.
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The researchers stopped the heart of laboratory swine kept at room temperature, declared them dead from cardiac arrest, waited 25 minutes, and then resuscitated them with high doses of oxygen using hyperbaric oxygen therapy. The American Heart Association statistics on sudden death have shown that if a patient's heart is not restarted within 16 minutes with CPR, medications, and electric shocks, 100% of patients die.

"To resuscitate any living organism after 25 minutes of heart stoppage at room temperature has never been reported and suggests that the time to successful resuscitation in humans may be extended beyond the stubborn figure of 16 minutes that has stood for 50 years," notes Dr. Keith Van Meter, Clinical Professor of Medicine and Chief of the Section of Emergency Medicine at LSU Health Sciences Center New Orleans, who led the study.

The study involved the use of three groups of laboratory swine. All swine underwent cardiac arrest for 25 minutes during which time they received no artificial breathing, CPR, medications, or electric shocks. After 25 minutes the swine were randomly divided into 3 groups. The first group remained at normal pressure. The second group was given standard-dose hyperbaric oxygen, and the third group was given high-dose hyperbaric oxygen, a dose that is nearly 1/3 more than the highest dose currently given to humans.

Advanced cardiac life support (ACLS) was started on animals in all groups for a two-hour resuscitation period. After the two-hour resuscitation period, four of the six animals in the high-dose hyperbaric oxygen group could be resuscitated. None of the subjects in the other groups were able to be resuscitated.

"The present study shows that short-term high-dose hyperbaric oxygen is an effective resuscitation tool and is safe in a small multiplace hyperbaric chamber," concludes Dr. Van Meter. "A rehearsed team can easily load a patient in cardiopulmonary arrest into a small multiplace chamber in the pre-hospital or hospital setting without interrupting CPR or advanced cardiac life support. Successful resuscitation at 25 minutes suggests that if high dose hyperbaric oxygen is used at the current ACLS limit of 16 minutes, a greater survival may be achieved in humans and allow application of more definitive treatment such as clot dissolving drugs."

The research team also included LSU Health Sciences Center New Orleans faculty Diana Barratt, MD, MPH, Heather Murphy-Lavoie, MD, Paul G. Harch, MD, James Moises, MD, and Nicolas Bazan, MD, PhD. and

Future studies are planned to further refine knowledge about this important addition to resuscitation and survival procedures.
Adapted from materials provided by Louisiana State University Health Science Center, via EurekAlert!, a service of AAAS.
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¿Que tratamiento estaría indicado en la necrobiosis lipoidica diabeticorum?

¿Que tratamiento estaría indicado en la necrobiosis lipoidica diabeticorum?
Respuesta
La búsqueda sobre necrobiosis lipoidica, ha localizado tán solo 8 ensayos clínicos, de los cuales 4 están realizados con un grupo control y todos realizados con un número pequeño de casos. La mayoría de artículos publicados, están basados en pequeñas series de casos (en muchas ocasiones de uno a cinco) con diferentes terapias. Reproducimos la revisión realizada en UpToDate 1 sobre el tratamiento de esta entidad clínica: “Habitualmente, el tratamiento de la necrobiosis lipoidica no es óptimo y debe ser mantenido de forma crónica. Para el tratamiento inicial valore la administración de un corticoide tópico de potencia moderado (por ejemplo crema de acetónido de triamcinolona al 0,1% tres veces al día). Si no hay mejoría en dos semanas, considere la utilización de dipropionato de betometasona dos veces al día, monitorizando la presencia de atrofia de piel. La inyección intralesional de triamcinolona (5 á 10 mg/ml de triamcinolona diluido con lidocaína hasta reducir a 2.5 a 5mg /ml) puede ser realizada con precaución si no hay úlceras y el riesgo percibido es bajo. Evite la utilización de corticoides tópicos o inyectables si existe cualquier tipo de ulceración y reduzca la potencia y la duración del corticoide a la más baja que pueda controlar la inflamación. La interconsulta o referencia del paciente están a menudo indicadas. Un informe basado en un caso informa de la posibilidad de que la crema de tacrolimus pueda ser de algún beneficio en etapas precoces de la enfermedad”. “Para enfermedad ulcerativa, un número de casos con tratamiento exitoso con agentes como ciclosporina, factor estimulante de la colonia granulocitos-macrófagos, altas dosis de nicotinamida, oxígeno hiperbárico, corticoides sistémicos, e infliximab han sido informados. Sin embargo no se ha identificado una terapia consistente y beneficiosa“. No incluidos en la revisión de Up todate, destacan: *Una serie de 30 pacientes tratados con psoralen más radiaciones ultravioleta A (PUVA) 2,muestran mejoría o desaparición de los síntomas en 16 pacientes, 10 no mejoraron y en cuatro la evolución fue mala. *Un ensayo clinico controlado (16 pacientes) con bajas dosis de acido acetil salicilico 3 o con dipiridamol (14 pacientes) 4 no mostraron mejoría en relación al placebo. La revisión publicada por e-medicine 5 concluye que no hay una definida una terapìa efectiva. Además del tratamiento con corticoides, informa de publicaciones de casos clínicos con mejoría mediante terapia con: nicotinamida, pentoxifilina, aspirina, dipiridamol, ticlopidina, clofazimina, tretinoina ,colágeno bovino tópicamente e inyecciones intralesionales con heparina. Referencias:1. Goldstein BG.Metabolic and inherited diseases affecting the skin. In: UpToDate, Rose, BD (Ed), UpToDate, Wellesley, MA, 2005. 2.De Rie MA, Sommer A, Hoekzema R, Neumann HA.Treatment of necrobiosis lipoidica with topical psoralen plus ultraviolet A.Br J Dermatol. 2002 Oct;147(4):743-7 3.Beck HI, Bjerring P, Rasmussen I, Zachariae H, Stenbjerg S.Treatment of necrobiosis lipoidica with low-dose acetylsalicylic acid. A randomized double-blind trial.Acta Derm Venereol. 1985;65(3):230-4. 4. Statham B, Finlay AY, Marks R.A randomized double blind comparison of an aspirin dipyridamole combination versus a placebo in the treatment of necrobiosis lipoidica.Acta Derm Venereol. 1981;61(3):270-1 5.Barnes Ch J.Necrobiosis Lipoidica.Last Updated: October 8, 2001 e-medicine . Total de artículos localizados e incluidos:5 I: Metaanálisis y/o revisiones sistemáticas:0 II: Ensayos clínicos:2 III: Cohortes, casos controles, serie de casos clínicos:1 IV: Consenso de profesionales:0 GU: Guías de práctica clínica:0 Otros:Revisión narrativa:2 Advertencia sobre la utilización de las respuestas. Las contestaciones a las preguntas formuladas, se elaboran con una finalidad exclusivamente formativa. Lo que se pretende, es contribuir con información al enriquecimiento y actualización del proceso deliberativo de los profesionales de la Medicina y de la Enfermería.Nunca deberán ser usadas como criterio único o fundamental para el establecimiento de un determinado diagnóstico o la adopción de una pauta terapéutica concreta. De ningún modo se pretende sustituir, avalar o tutelar la responsabilidad del médico. Esta deriva de sus propias decisiones y solo por él debe ser asumida, no pudiendo ser compartida por quienes solo le han informado. La Consejeria de Sanidad y el Servicio Murciano de Salud, rechazan a priori toda responsabilidad respecto de cualquier daño o perjuicio que se pueda imputar a la utilización total o parcial de la información aportada y que fue solicitada previamente por el profesional médico ó de enfermería.

FFECT OF HYPERBARIC OXYGEN ON THE REGENERATION OF EXPERIMENTAL CRUSH INJURIES OF NERVES

Revista do Hospital das Clínicas
Print ISSN 0041-8781
Rev. Hosp. Clin. vol.54 n.3 São Paulo Jun. 1999


EFFECT OF HYPERBARIC OXYGEN ON THE REGENERATION OF EXPERIMENTAL CRUSH INJURIES OF NERVES

Paulo Tuma Jr., Mariza D'Agostino Dias, Gino Arrunátegui, Gustavo Gibin Duarte, Alexandre Wada, Armando Santos Cunha and Marcus Castro Ferreira

RHCFAP/2967

TUMA Jr. P et al. - Effect of hyperbaric oxygen on the regeneration of experimental crush injuries of nerves . Rev. Hosp. Clín. Fac. Med. S. Paulo 54 (3): 81 - 84,1999.



SUMMARY: Hyperbaric oxygen has been successfully used on treatment of acute ischemic injuries involving soft tissues and chronic injuries. In nerve crush injuries, the mechanisms involved are very similar to those found in ischemic injuries. Consequently, it is logical to hypothesize that hyperbaric oxygen should improve nerve repair, which is a critical step on functional recovery. In the present study, we created standard nerve crush injuries on sciatic nerves of rats, which underwent treatment with hyperbaric oxygen. Results were assessed by functional evaluation using walking-track analysis. The functional recovery indexes observed did not differ from control group. We concluded that hyperbaric oxygen therapy, in the schedule used, had no influence on functional recovery after nerve crush injuries.


DESCRIPTORS: Hyperbaric oxygen. Nerve regeneration. Nerve injury. Sciatic function index. Experimental study.

Therapy with hyperbaric oxygen (HBO) is an adjuvant treatment in some cases of acute trauma with ischemia, such as crush injuries of extremities, compartmental syndrome, poorly healing injuries, ischemic flaps, and radionecrosis of bone1.

Crush injuries and section of nerves may manifest a physiopathology similar to that associated with ischemia of muscle and skin flaps. In the initial period after the nerve damage, swelling and edema occur, as indicated by higher nerve weight caused by increase of water1.

Previous studies showed improvement in functional recovery when therapy with hyperbaric oxygen is used either after transection and suture2 or when autologous nerve grafting is interposed3 in rat the sciatic nerve model. However, the same results were not seen with nerve tubulization after transection1, and in crush injuries of rat fibular nerves4.

Fibular nerve has better vascularization, compared to sciatic nerve, due to its smaller transverse section area4. The present study was designed to evaluate the influence of HBO in the functional recovery after crush injury in rats, using the sciatic nerve, which is theoretically more susceptible to ischemia than the fibular nerve.

MATERIAL AND METHODS

Surgical Procedure

Twenty Wistar male rats, weighting from 300 to 350 g, with ages of around 8 weeks, were operated on under anesthesia using chloral hydrate in a concentration of 10%, 400 mg/kg, intra-peritoneal injection. An incision was made dorsally on the right thigh. Through a muscle splitting incision, the sciatic nerve was exposed from the notch to its first division (Figure 1).

The crush injury of 1.5 mm was performed on the nerve, using a hemostatic "mosquito" forceps (Figure 2). As described by Dash5, the nerve was crushed 1 cm proximally to the bifurcation, for 5 seconds, with the instrument closed to the first notch (Figure 3). After the procedure, the muscle and skin were closed, and the animals were placed in separated cages, with water and food ad libitum.

Hyperbaric Oxygen Therapy

Animals were randomized into two groups, A and B (Table 1). In the first group (A), animals received oxygen in a 100% concentration in an individual hyperbaric chamber, model Seechrist®, under a 2.8 atmospheres pressure for 30 minutes, twice a day, during three consecutive days. Therapy started at the first hour after the operation. The other group (B) did not receive hyperbaric oxygen after the injuries.

Functional Evaluation

Functional recovery was assessed using the walking-track analysis, according to the method previously described by Medinaceli et al.6 and modified by Bain et al7. The analyses were made before the surgery, and 2, 15 and 30 days after.

In order to create foot prints on paper, animals had their posterior foot painted in blue ink and were placed on white paper in a track. Afterwards, the prints were measured, and the following measurements were taken: the distance between first and fifth toes (toe spread - TS), distance between second and fourth toes (intermediate toe spread - ITS), and the total length of the footprint (print length - PL).

The measures were used to calculate the Sciatic Function Index for each animal, as proposed by Bain7:

SFI= [-38.3 x (PLO - PLN)¸ PLN] +

[109.5 x (TSO - TSN)¸TSN] +

[13.3 x (ITSO - ITSN)¸ITSN] - 8,8

PLO = length of the operated print

PLN = length of the normal print

TSO = operated toe spread

TSN = normal toe spread

ITSO = intermediate operated toe spread

ITSN = intermediate normal toe spread

Using this formula, the Sciatic Function Index (SFI) was calculated, and the values were classified as follows::

SFI = 0 +/- ® normal sciatic function

SFI = -100 +/- ®12 Æ complete dysfunction

Statistical Analysis

The variable SFI was presented descriptively in a table containing mean, standard deviation, median, minimal values, and maximal values, for each group and evaluation condition.

The two factors, group and evaluation condition, were studied through the mean profile analysis, and the following hypotheses were tested:

• H01: the mean profiles are parallels and the groups have the same behaviour during the studied conditions.

• H02: the mean profiles are the same, and there is no difference between the means of the two groups on the conditions studied.

• H03: there is no influence of the condition factor, and the means are constant during the different conditions.


Significance level in this study was <0.05.

RESULTS

A SFI near 0 was observed in the measures made before the injuries, demonstrating normal function. Two days after the injury, the SFI decreased in both groups. After 15 days, the SFI was half-way towards zero, and in 30 days, the SFI was nearest to zero of the three measurements taken after injury (Table 2 and Graph 1).

There was no statistically significant difference between the HBO and control groups (Table 3).

DISCUSSION

Some nerve injuries are followed by hypoperfusion and edema. These changes can be detected almost immediately after a nerve injury1.

In any acute ischemic tissue, cellular changes occur, and they disturb the regulation of flow through the capillary membranes, leading to edema. This edema seems to be important in maintaining ischemia, because it compresses the microcirculation and decreases tissue perfusion. When the circulation is restored after long ischemic periods, physiologic shunts are opened, increasing the edema, resulting in a paradoxic ischemia (no-reflow phenomenon)8. HBO used early might interfere with this sequence by promoting vessel constriction, decreasing the flow and thus the edema. Hyperoxygenation would compensate for the decrease of flow, maintaining tissue oxygenation in suitable level8. Another possible mechanism of action associated with HBO is the decrease in the neutrophil linkage to the endothelial wall, which minimizes the delivery of free radicals produced by the reperfusion phenomenon8,9.

The intensity of these harmful factors on the neural structures, however, has not been established. Other possible actions of HBO would consist of increasing production of vascular and neural growth factors, which improves the tissue perfusion1. In spite of all these possible mechanisms, the exact cellular mechanism of action of HBO is not still completely understood1,9,10.

Several schedules for treatment with HBO have been proposed, but there is not a standardized model that would be adequate for use in experimental animals. Pressures of more than three atmospheres during more than three hours, more than twice a day, are considered to have potential toxicity11. In this study, HBO was used an hour after the operation, and during three consecutive days, with a pressure of 2.8 atmospheres, for 30 minutes, twice a day. This proposed schedule seems to be adequate for this experimental model, and morbidity or death associated to the HBO was not observed.

Previous reports showed improve on functional recovery after rat sciatic nerve transection and autologous graft with the use of HBO2,3. On the other hand, the same was not observed in transections treated with tubulization1, and in crush injuries of rat fibular nerves4.

The crush injury differs from the transection injury because it produces axonotmesis, a functional impairment that returns to normal almost completely after three weeks from the injury, as observed in our control group, confirming the data by Dash et al5. Transection causes a injury in which spontaneous regeneration occurs only rarely. Consequently, HBO might have a more significant influence on nerve injuries with complete interruption by regulating the nerve environment, than it does with crush injuries, for which the external factors are less critical.

Results observed in this study agreed with the experiment performed by Santos et al.4 using crush injury, although the authors had used the fibular nerve and a different HBO schedule. Fibular nerve has better vascularization, compared to sciatic nerve. Although both have perineurial circulation, the fibular nerve has better vascularization because of its smaller transverse section area4. This difference seems not to interfere with functional evaluation after crush injuries of nerves in animals exposed to HBO.



RHCFAP/2967

TUMA Jr. P e col. - Efeito da oxigenioterapia hiperbárica na regeneração de lesões experimentais de nervos. Rev. Hosp. Clín. Fac. Med. S. Paulo 54 (3): 81 - 84, 1999.
O oxigênio hiperbárico exerce efeitos comprovadamente benéficos no tratamento de lesões isquêmicas agudas de partes moles e em feridas de difícil cicatrização. Nas lesões neurais por esmagamento, os mecanismos fisiopatológicos assemelham-se aos efeitos dependentes da isquemia tissular. Portanto, a terapia com oxigênio hiperbárico teria participação nos processos de reparação neural, que constitui um dos pontos críticos para a recuperação funcional após as lesões por esmagamento de nervos periféricos. Neste estudo, foram realizadas lesões por esmagamento em nervo ciático de ratos, submetidos à terapia com oxigênio hiperbárico no pós-operatório. Os resultados foram quantificados através de avaliação funcional pelo método de "walking-track analysis". Os índices de recuperação funcional observados não diferiram dos observados no grupo controle. Portanto, verificou-se que a terapia com oxigênio hiperbárico, no esquema proposto, não teve influência na recuperação funcional após lesões neurais por esmagamento.



DESCRITORES: Oxigênio hiperbárico. Regeneração neural. Lesão neural. Índice de função ciática. Estudo experimental.

REFERENCES

1. SANTOS PM, ZAMBONI WA, WILLIAMS SL et al. - Hyperbaric oxygen treatment after rat peroneal nerve transection and entubation. Otolaringol Head Neck Surg, 1996; 114: 424-434.

2. ZAMBONI WA, BROWN RE, ROTH AC, et al. - Functional evaluation of peripheral nerve repair and the effect of hyperbaric oxygen. J Reconstr Microsurg, 1995; 11: 27-29.

3. GINGRASS M, ZAMBONI WA, BROWN RE, et al. - The effect of high tension oxygen on nerve regeneration in a nerve graft model. J Reconstr Microsurg, 1993; 9: 158.

4. SANTOS PM, WILLIAMS SL & COVEY J - Peroneal motor nerve crush injury and hyperbaric oxygen effect . Laryngoscope, 1995; 105: 1061-1065.

5. DASH H, KONONOV A, PRAYSON RA, et al. - Evaluation of nerve recovery from minimal-duration crush injury. Ann Plast Surg, 1996; 37: 526-531.

6. DE MEDINACELI L FREED WJ & WYATT RJ. - An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp Neurol, 1982; 77: 634-643.

7. BAIN JR, MACKINNON SE & HUNTER DA. - Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve injuries in the rat. Plast Reconstr Surg, 1989; 83: 129-138.

8. NYLANDER G, LEWIS D, NORDSTROM H, et al. - Reduction of postischemic edema with hyperbaric oxygen. Plast Reconstr Surg, 1985; 76 : 596-601.

9. ELLIS FR & DEWAR KM - Effect of hyperbaric oxygen on nerve tissue. Br J Anesth, 1970; 42: 800.

10. MUKOYAMA M, IIDA M & SOBUE I - Hyperbaric oxygen therapy for peripheral nerve damage induced in rabbits with Clioquinol. Exp Neurol, 1975; 47: 371-380.

11. DAVIS JC - Hyperbaric oxygen therapy: a committee report. Bethesda, Undersea Medical Society, 1983.


Division of Plastic Surgery, University of São Paulo School of Medicine - São Paulo, Brazil.

¿Qué es la oxigenación hiperbárica (OHB)?

La oxigenación hiperbárica como medicina preventiva
¿Qué es la oxigenación hiperbárica (OHB)?

El tratamiento con oxigeno hiperbárico es un tipo de terapia no invasiva. El paciente respira tranquilamente 100% de oxigeno mientras permanece en una cámara presurizada a una presión dos o tres veces superiores a la presión atmosférica ambiental.

Es la única terapia indicada en ciertos casos y en muchas otras ayudas en el tratamiento de enfermedades y problemas clínicos o quirúrgicos difíciles, aparte de producir un efecto revitalizador en todos los tejidos.

El quid del tratamiento con oxigeno hiperbárico radica en la factibilidad que presenta el plasma sanguíneo (que es el liquido donde flotan los glóbulos rojos) de permitir la dilución del oxigeno, incrementando de diez a quince veces la concentración de este elemento, lo que produce un incremento cuatro veces mayor de difusión de oxigeno desde los capilares funcionales a las células.
Todo esto independientemente de que el nivel de oxigeno llevado por la hemoglobina de los glóbulos rojos permanezca igual, que es lo que nos sucede normalmente cuando respiramos durante las 24hrs del día.

Esta moderna terapia de Oxigenación Hiperbárica, no sólo está indicada para los pacientes que sufren determinada enfermedad, sino que puede ser utilizada por todas las personas con el propósito de revitalizar sus órganos y de esta manera prevenir enfermedades, mantenerse saludables y prologar la vida con calidad.

Existen básicamente dos tipos de cámaras hiperbáricas:
Cámaras Multiplaza

Las cámaras multiplaza son mucho más espaciosas, los pacientes están cómodamente sentados y pueden ser fabricadas desde 6 hasta 20 asientos, según el modelo.



Cámara Monoplaza

Las cámaras monoplaza son para tratamientos de una sola persona, generalmente en camilla telescópica incluida en la camilla.
La oxigenación hiperbárica aplicada en las enfermedades

La oxigenación hiperbárica es indicada para las siguientes aplicaciones:

"Tipo I" (Aceptadas)

* Radionecrosis de tejidos blandos y óseos.
* Enfermedad de la descompresión.
* Intoxicación aguda por monóxido de carbono (CO) y humo.
* Embolia gaseosa aguda.
* Gangrena gaseosa.
* Sepsis por anaerobios y/o bacteroides.
* Oteomelitis refractaria.
* Infecciones en los tejidos por flora aerobia y/o anaerobia.
* Injertos o colgajos comprometidos.
* Micosis refractarias (mucormicosis y actinomicosis).
* Edema cerebral agudo.
* Quemaduras.
* Anemia por hemorragia aguda.
* Ileo-paralítico.
* Síndrome de aplastamiento y compartimental.
* Cicatrización de heridas.
* Tejidos dañados por radiaciones.
* Abscesos intrabdominales e intracraneales.

"Tipo II" (Recomendadas)

* Lesiones traumáticas de médula espinal en su periodo inicial.
* Injerto de huesos.
* Accidente cerebro-vascular agudo (trombótico o hemorrágico).
* Consolidación de fracturas.
* Lepra lepromatosa.
* Meningitis.
* Colitis seudo membranosa.
* Mielitis, cistisis, enteritis, proctitis, post radiación.
* Esclerosis múltiple.
* Insuficiencia arterial retiniana aguda.
* Pioderma gangrenoso.
* Síndromes isquémicos periféricos.
* Úlceras de miembros (de estasis, decúbito, varicosas).
* Pie diabético.
* Insuficiencia vascular cerebral.
* Edema cistoides.
* Otitis maligna del diabético.
* Migraña rebelde a tratamiento.
* Parálisis Cerebral Infantil
* Vértigo
* Sordera Súbita.
* Lesiones de los deportistas.
* Apoyo a la terapia de rehabilitación en neurología y ortopedia
* Apoyo en cirugía plástica y reconstructiva

"Tipo III" (En estudio)

* Guillain Barré.
* Parálisis facial periférica.
* Colitis ulcerosa.
* Vasculitis.
* Enfermedad de Perthers.
* Demencia Post Infarto
* Crisis aguda de la drepanocitosis.
* Autismo.
* Hepatitis crónica.
* Otras

Consideraciones Fisiológicas y Bioquímicas de la oxigenación hiperbárica

En condiciones atmosféricas normales, la presión parcial de oxígeno es de aproximadamente 150 mmHg. en el aire inspirado y de 100 mmHg en el aire alveolar. La inhalación de oxígeno puro en tales condiciones, eleva la presión de oxígeno alveolar a 673 mmHg, según se observa en el siguiente cuadro:

Atmósfera Absoluta


Presión ambiental


Presión 02 Alveolar




mmHg


mmHg

1


760


673

2


1520


1433

3


2280


2193

4


3040


2953

5


3800


3713

6


4560


4473

Cabe anotar que a una ATA. (atmósfera absoluta), los restantes mmHg. Hasta los 760 mmHg. De presión ambiental son a expensas de vapor de agua y 40 mmHg de gas carbónico. A medida que vamos incrementando la presión ambiental, estos últimos valores no varían, siendo el aumento de la presión total a partir del nivel tensional de oxígeno.

La hemoglobina con un nivel de saturación de oxígeno de 97% en condiciones normales, se torna totalmente saturada con la inhalación de oxígeno puro a presión ambiental (1 atmósfera absoluta), por lo que el efecto de la aplicación hiperbárica para la hemoglobina es prácticamente despreciable. Sin embargo, cuando el individuo respira oxígeno puro en condiciones hiperbàricas, la presión de oxígeno alveolar aumenta proporcionalmente y en consecuencia también se incrementa la presión de oxígeno intra-arterial que sube 760 mmHg. por cada atmósfera. Una vez que la hemoglobina ya se encuentra saturada, ese aumento se hace exclusivamente a partir de la dilución física de este gas en el plasma por gradiente osmótica por efecto de la ley de Henry: “a temperatura constante, el volumen de un gas que se disuelve en un líquido es proporcional a la presión parcial de dicho gas”.

Así, a una presión absoluta de 3 atmósferas, la presión del oxígeno alveolar será superior a 2000 mmHg. y habrá un incremento de cerca de 6 volúmenes por ciento en el oxígeno intra-arterial en relación a los niveles posibles a presión atmosférica. La oxigenación de los tejidos en estas condiciones, pasa a ser pues, independiente de la hemoglobina.

Esto condiciona que a 3 atmósferas absolutas (presión habitual de tratamiento), la difusión de oxígeno a nivel tisular se incrementa en 325 por ciento en relación a la que se obtiene respirando dicho gas a 1 atmósfera y en 2100 por ciento si la comparación se hace referida a la tasa de oxigenación tisular normal, respirando aire a presión atmosférica.

Tens S. A. de C. V., es la empresa líder en México en la venta de equipos Tens y Electroestimuladores, ampliando su giro a productos para electromedicina, y equipos para las especialidades médicas de rehabilitación, terapia física, medicina del deporte, geriatría, reumatología, ortopedia, entre otras.

Conozca el Perfil, Productos, Dirección y Teléfono de Tens S. A. de C. V.

O bien, haga contacto directo con Tens S. A. de C. V para solicitar mayor información sobre la cámara multiplaza o cámara monoplaza.

Medicina Hiperbarica en niños deportistas en Chile

En las últimas semanas me ha tocado coordinar varios tratamientos de cámara hiperbárica en lesiones deportivas. Algunos pacientes son adolescentes y otros, adultos. Varios de estos casos han sido de conocimiento público y se comentan en diarios, televisión, radio, etc.

Tengo la suerte de trabajar en el Hospital Fach, que es unos de los pocos lugares en Santiago y en Chile donde podemos trabajar con la medicina hiperbárica. Todos estos casos de lesiones deportivas tratadas con cámara hiperbárica se han hecho en mi hospital.
Aquí un ejemplo
En prensa hemos podido ver varios conceptos teóricos sobre el tema, muchos de ellos equivocados, así que aquí hay algunas guías para que entiendan de qué se trata:
- La cámara hiperbárica es un recinto cerrado o sellado, donde pueden estar varias personas (multiplaza), como una habitación; o un cubículo donde puede estar una persona o paciente acostado (monoplaza).
- El aire que respiramos tiene una concentración de oxígeno de un 21%
- El aire dentro de una cámara hiperbárica tiene una concentración de oxígeno de 100%
- La presión del aire dentro de una cámara hiperbárica es mayor a la presión del aire atmosférico.
- Entonces: un lugar cerrado, con presión alta y concentración de oxígeno al 100%

El uso de la cámara partió para atender la enfermedad por descompresión inadecuada (EDI) o "mal de presión" de los buzos. Después se ha extendido a una serie de enfermedades o problemas como:
- Intoxicación por monóxido de carbono
- Heridas complejas de cierre difícil, isquémicas y/o infectadas
- Infecciones óseas (osteomielitis)
- Infecciones graves como gangrenas, celulitis infectadas, etc.
- Quemaduras
- Pie diabético
- Etc.
La medicina hiperbárica se basa en varias leyes físicas de los gases. De esta manera el oxígeno a presión se distribuye fácilmente en tejidos, donde en determinadas situaciones no puede llegar. El oxígeno estimula varios procesos de reparación y cicatrización, acelerando tiempos de recuperación, aumentando concentraciones locales de oxígeno, etc.

Dentro de las variadas alternativas de la Cámara hiperbárica, está su uso en medicina deportiva y lesiones deportivas. Este uso no está muy explotado en Chile y el lugar con más experiencia en Chile, es la cámara hiperbárica del Hospital Fach. Junto a la indicación histórica del oxígeno hiperbárico en buzos y su descompresión inadecuada al ascender a superficie (buzos de pesca, caza deportiva, competidores, etc), podemos agregar lesiones de piel en andinistas o excursionistas (quemaduras). Pero lesiones deportivas propiamente tal, tenemos experiencia abundante en recuperar lesiones de sobreuso en cadetes militares, en especial, las fracturas de stress y periostitis.

En los últimos meses se han atendido en la cámara hiperbárica una serie de deportistas de alto rendimiento, que necesitaron una recuperación rápida de sus lesiones complejas. Dentro de los adolescentes, por ejemplo, un par de fracturas de stress del quinto metatarsiano, que siempre resultan ser un dolor de cabeza para un médico de equipo (una futbolista logró recuperarse para jugar el mundial juvenil de fútbol este mes). Y otros casos de desgarros musculares y fracturas de stress en futbolistas adultos

Pueden revisar algunos casos en internet
Incluso con fotos
O casi epidemias de lesiones deportivas, bajo presión por las fechas del torneo de fútbol, etc.
Si necesitan un repaso sobre fracturas del quinto metatarsiano, pueden hacer click aquí

ERRORES COMUNES DE CONCEPTOS:
-No es lo mismo la cámara hiperbárica, que la CÁMARA HIPOBÁRICA. Hay mucha confusión en prensa sobre el tema. Y una de las causas pricipales de confusión, es que dentro del hospital Fach, tenemos también la ¿única? cámara Hipobárica del país. Está en el Centro de Medicina Aeroespacial (CMAE), y como adivinarán, los que entran a esa cámara, están en un lugar con concentración baja de oxígeno. Simulando condiciones de altura. Se ocupa para entrenar pilotos de avión, estudios de fisiología de altura y en los últimas dos eliminatorias de mundial de fútbol, se hicieron programaciones muy serias para que la selección entrene dentro de esta cámara, antes de los partidos contra Bolivia (los dos partidos ganados, para los que tienen buena memoria). Pero hablar de cámara HIPOBÁRICA, da para otro tema en este blog

- Invento: leí en un diario que uno de nuestros futbolistas estaba en la cámara ISOBÁRICA de la Fach (ISO: igual, Baro: presión). Esto ocurrió sólo en la imaginación del periodista y ya puede patentar su invento

-Otro error: en varias partes leí que nuestros futbolistas estaban recuperándose de sus lesiones en la cámara hiperbárica, que simula el entrenamiento de altura y que es la misma que la selección ocupó para ir a aBolivia (confusión total de conceptos)
CASO CLÍNICO:

Futbolista, 15 años. Seleccionado en su club y selección nacional.
Fractura de stress 5º metatarsiano. Rasgo de fractura incompleto
Luego de varias reuniones y discusiones, decidimos tratarlo "en forma ortopédica", es decir, no quirúrgica. Tuvo 36 sesiones de cámara hiperbárica. Tratado con bota ortopédica, sin carga de peso 1 mes y luego carga progresiva. Lo dimos de alta a los 3 1/2 meses. Se prepara ahora para una gira en enero de un mes por Asia

Oxígeno hiperbárico para la sensibilización tumoral a la radioterapia

Oxígeno hiperbárico para la sensibilización tumoral a la radioterapia

Bennett M, Feldmeier J, Smee R, Milross C

Resumen
Respirar oxígeno hiperbárico durante la radioterapia para el tratamiento de cáncer puede reducir el riesgo de muerte y recurrencia local dentro de cinco años para el cáncer de cabeza y cuello, y recurrencia dentro de los dos años para el cáncer de cuello uterino.

Respirar oxígeno hiperbárico incluye la colocación de los pacientes en una cámara especialmente diseñada y a menudo, se usa para aumentar el efecto de la radioterapia y, por lo tanto, produce una mejoría en la mortalidad y en el nuevo crecimiento tumoral. Se encontraron algunas pruebas de que las personas con cáncer de cabeza y cuello tienen menor probabilidad de morir dentro de los cinco años si son tratadas de esta manera, y pruebas de que el nuevo crecimiento del tumor en el sitio original es menos probable para el cáncer de cabeza y cuello y cervical. Sin embargo, el oxígeno hiperbárico solamente puede ser efectivo cuando la radioterapia se administra en un número excepcionalmente pequeño de sesiones, cada una con una dosis relativamente alta. El oxígeno hiperbárico no parece funcionar en otros cánceres estudiados. Las conclusiones se basan en 19 ensayos aleatorios con más de 2000 pacientes.

Éste es el resumen de una revisión Cochrane traducida. La Colaboración Cochrane prepara y actualiza estas revisiones sistemáticas. El texto completo de la revisión traducida se publica en La Biblioteca Cochrane Plus (ISSN 1745-9990). De La Biblioteca Cochrane Plus, número 2, 2008. Oxford, Update Software Ltd. Todos los derechos están reservados.

Fecha de la modificación significativa más reciente: 16 de julio de 2005
Resumen
Antecedentes

El cáncer es un trastorno frecuente y la radioterapia es un tratamiento bien establecido para algunos tumores sólidos. El oxígeno hiperbárico puede mejorar la capacidad de la radioterapia de matar células cancerosas hipóxicas, de modo que la administración de radioterapia a medida que se respira oxígeno hiperbárico puede resultar en la reducción de la mortalidad y recurrencia tumoral.
Objectivos

Evaluar los beneficios y daños de la radioterapia a medida que se respira oxígeno hiperbárico.
Estrategia de búsqueda

En noviembre 2004 se hicieron búsquedas en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (CENTRAL), (The Cochrane Library, número 3), MEDLINE, EMBASE , CINAHL, DORCTHIM y listas de referencias de artículos. Se hicieron búsquedas manuales en revistas relevantes.
Criterios de selección

Estudios aleatorios y cuasialeatorios que comparan el resultado de tumores malignos después de la radioterapia a medida que se respira oxígeno hiperbárico versus aire (con o sin tratamiento de simulacro).
Recopilación y análisis de datos

Tres revisores evaluaron de forma independiente la calidad de los ensayos pertinentes mediante el método de Schulz (Schulz 1995) y extrajeron los datos de los ensayos incluidos.
Resultados principales

Diecinueve ensayos contribuyeron con esta revisión (2286 pacientes: 1103 asignados al oxígeno hiperbárico y 1153 al control). Con el oxígeno hiperbárico, hubo una reducción de la mortalidad en los cánceres de cabeza y cuello ya sea al año y cinco años después del tratamiento (Riesgo Relativo [RR]: 0,83; P = 0,03; número necesario a tratar [NNT] = 11 y RR: 0,82; P = 0,03; NNT = 5 respectivamente), así como un mejor control tumoral local a los tres meses (RR con OTHB 0,58; P = 0,006; NNT = 7). El efecto de oxígeno hiperbárico varió con los diferentes planes de fraccionamiento. La recurrencia tumoral local fue menos probable con el oxígeno hiperbárico al año (cabeza y cuello; RR: 0,66; P < 0,0001; NNT = 5), a los dos años (cuello uterino; RR 0,60; P = 0,04; NNT = 5) y a los cinco años (cabeza y el cuello; RR 0,77; P = 0,01). Cualquier ventaja se logra con el costo de algunos efectos adversos. Hubo un aumento significativo en la tasa de lesión tisular por radiación grave (RR: 2,35; P < 0,0001, [número necesario a dañar [NND] = 8) y de posibilidades de crisis epilépticas durante el tratamiento (RR: 6,76; P = 0,03; NND = 22) con oxígeno hiperbárico.
Conclusiones de los revisores

Hay algunas pruebas de que el oxígeno hiperbárico mejora el control tumoral y la mortalidad local para los cánceres de cabeza y cuello, y la recurrencia tumoral local en los cánceres de cabeza y cuello, y cuello uterino. Estos beneficios solamente pueden ocurrir con esquemas de fraccionamiento inusuales. El oxígeno hiperbárico se asocia a efectos adversos significativos que incluyen crisis epilépticas por toxicidad del oxígeno y lesiones tisulares graves por radiación. Los fallos metodológicos y de información de los estudios principales incluidos en esta revisión exigen una interpretación cautelosa. Se necesitan realizar más investigaciones para el cáncer de cabeza y cuello, pero probablemente no se justifican para el cáncer vesical. Hay pocas pruebas disponibles que traten las neoplasias en otros sitios anatómicos en las que basar una recomendación.
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The hyperbaric oxygen preconditioning-induced brain protection is mediated by a reduction of early apoptosis after transient global cerebral ischemia

Neurobiol Dis. Author manuscript; available in PMC 2009 January 1.
Published in final edited form as:
Neurobiol Dis. 2008 January; 29(1): 1–13.
Published online 2007 July 28. doi: 10.1016/j.nbd.2007.07.020.

The hyperbaric oxygen preconditioning-induced brain protection is mediated by a reduction of early apoptosis after transient global cerebral ischemia

Robert P. Ostrowski,1 Gerhart Graupner,2 Elena Titova,1 Jennifer Zhang,1 Jeffrey Chiu,1 Neal Dach,1 Dalia Corleone,1 Jiping Tang,1 and John H. Zhang1,3,4
1 Department of Physiology and Pharmacology, Loma Linda University, USA
2 Department of Pediatrics, Loma Linda University, USA
3 Department of Neurosurgery, Loma Linda University, USA
4 Department of Anesthesiology, Loma Linda University, USA
Correspondence to: Dr John H. Zhang, Department of Physiology & Pharmacology, Risley Hall, Room 219, Loma Linda University School of Medicine, Loma Linda, CA 92350, Tel: (909) 558–4723; Fax: (909) 558–0119, E-mail: johnzhang3910@yahoo.com
Small right arrow pointing to: The publisher's final edited version of this article is available at Neurobiol Dis.
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Abstract
We hypothesized that the brain-protective effect of hyperbaric oxygen (HBO) preconditioning in a transient global cerebral ischemia rat model is mediated by the inhibition of early apoptosis.

One hundred ten male Sprague Dawley (SD) rats (300–350 g body weight) were allocated to the sham group and three other groups with 10 minutes of four-vessel occlusion, untreated or preconditioned with either 3 or 5 hyperbaric oxygenations. HBO preconditioning improved neurobehavioral scores and reduced mortality, decreased ischemic cell change, reduced the number of early apoptotic cells and hampered a conversion of early to late apoptotic alterations. HBO preconditioning reduced the immunoreactivity of phosphorylated p38 in vulnerable neurons and increased the expression of brain derived neurotrophic factor (BDNF) in early stage post-ischemia. However, preconditioning with 3 HBO treatments proved less beneficial than with 5 HBO treatments.

We conclude that HBO preconditioning may be neuroprotective by reducing early apoptosis and inhibition of the conversion of early to late apoptosis, possibly through an increase in brain BDNF level and the suppression of p38 activation.
ences

Introduction

Hyperbaric oxygen preconditioning has been shown to have neuroprotective effects against focal and global cerebral ischemia (Xiong et al., 2000; Wada et al., 2001). It has been proposed as preconditioning treatment to prevent brain injury during major surgery (Wada et al., 2001). However the mechanism is not fully understood and more evidence is needed for HBO treatment to be accepted clinically (Prass et al., 2000).

The majority of studies examined HBO preconditioning effects on a delayed brain injury (Wada et al., 1996) that involves cell death in CA1 and layers 2 and 5 in the cerebral cortex occurring at least 12 hr after global ischemia (Lipton, 1999). However, the substantial benefit of HBO may occur in the early phase after ischemia, which, in turn, may be critical to the outcome of the protection against delayed brain injury. Additionally, the impact of HBO preconditioning on cortical damage has been investigated with less scrutiny than the effect on hippocampal cell death, despite established sensorimotor neurological deficits that occur acutely after global cerebral ischemia (Block 1999).

HBO preconditioning should have a powerful anti-apoptotic effect, as apoptosis is a dominant form of hippocampal cell death after global cerebral ischemia (Nitatori et al., 1995). Apoptosis has not yet been shown to occur in the early phase after global ischemic insult despite studies showing acute caspase activation, highly indicative of apoptotic pathway (Krajewska et al., 2004). Thus, hyperbaric oxygenation pre-conditioning may have an effect on early apoptosis but has yet to be examined for such an effect.

Neutrophins are candidate genes underlying effects of HBO preconditioning. In the brain HBO can induce brain derived neurotrophic factor (BDNF) (Chavko et al., 2002) whereas HBO preconditioning has been shown to induce neurotrophin receptor p75 NTR (Hirata et al., 2007). Downstream effects of BDNF may involve a suppression of p38/MAPK activity by inhibiting p38/MAPK phosphorylation (Yamagishi et al., 2003). p38/MAPK qualifies as fast-response signal, as it is activated in vulnerable neurons within minutes after global cerebral ischemia (Sugino et al., 2000b). Apoptosis through p38/MAPK is induced along pathways involving the transcriptional factor AP-1, p53 phosphorylation and subsequent caspase activation (Chen et al., 2003). Inhibition of p38/MAPK has been proven beneficial for cell survival in conditions of focal and global cerebral ischemia (Sugino et al., 2000b; Barone et al., 2001). Therefore, it is conceivable that an increase in BDNF protein levels due to HBO may be part of an anti-apoptosis mechanism targeting a proapoptotic p-38-dependent pathway in neurons.

Past studies of HBO preconditioning used the 5 courses of HBO treatments (Wada et al., 1996). This may however be problematic for the practical reasons. Recently, three HBO treatments applied within 24 hr before anticipated brain insult established a clinically effective preconditioning regimen (Alex et al., 2005).

We hypothesized that HBO preconditioning reduces early apoptosis and apoptosis progression possibly through induction of BDNF, suppression of p38/MAPK phosphorylation and reduced caspase-3 activation in the rat model of transient global cerebral ischemia. We also evaluated the neuroprotective effects of 5 times HBO versus 3 times HBO, which seems more feasible in the clinical setting.


Material and Methods

Animal groups and a model of global cerebral ischemia
One hundred ten male SD rats were divided into four groups: a sham operation (n=23); global ischemia induced by four vessel occlusion (4VO, n=35), sacrificed at 2 hr 45 min and 6, 24, 72 hr and 7 days; and two global ischemic groups preconditioned with either 3 or 5 HBO treatments sacrificed as above (3HBO+4VO; n=29 or 5HBO+4VO; n=23). All surgical and euthanasia procedures were performed under deep anesthesia with Ketamine (100 mg/kg) and Xylazine (10 mg/kg) i.p. injection. The animals were intubated and mechanically ventilated during the surgical procedures. Atropine at a dose 0.05 mg/kg was given to reduce secretion in the respiratory tract. The four-vessel occlusion rat model (Pulsinelli, Brierley 1979) with modifications to the one stage anterior approach, recently established in our lab, was used (Yamaguchi et al., 2005). Briefly, the skin was incised on the neck and subcutaneous connective tissue and muscles were gently retracted. The trachea and esophagus were gently retracted to the right side. Cervical vertebral bodies were exposed and the bilateral vertebral arteries were occluded using electrosurgical coagulator between the second and third transverse processes. Next, both common carotid arteries were occluded with microvascular clips for a period of 10 minutes. The rectal temperature was maintained at 36.9–37.4°C by means of a heating lamp during surgery and continued to 2 hours after surgery. Femoral arteries were cannulated in subsets of rats for BP measurements and blood gas analyses. Blood Glucose levels were measured before and after ischemia or sham surgery. All animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at Loma Linda University.

HBO preconditioning paradigms
Each course of hyperbaric therapy lasted 1 hr and involved pure oxygen at 2.5 atmospheres absolute (2.5 ATA). Rats were pressurized in a research hyperbaric chamber (1300B, Sechrist) with an oxygen flow of 22 L/min. Compression and decompression was maintained at a rate of 5 psi/min. Two regimens of preconditioning were used: 5 treatments with one treatment per day; the last dive 24 hr before ischemia (5HBO) or 3 treatments within 24 hr: at 24 hr, 12 hr and 4 hr before ischemic insult (3HBO).

Formalin perfusion and Nissl stain
For all histological studies, the rats were perfused intracardially with 60 mL of cold PBS, followed by 300 mL of cold buffered 10% formalin. Brains were postfixed for 72 hr in the formalin at 4°C, then cryoprotected in 30% sucrose/PBS until they sank. Ten micrometers thick frozen sections were cut in the cryostat as described previously (Ostrowski et al., 2005). For Nissl staining, the sections were dried, rehydrated and immersed in 0.5% cresyl violet for 2 min. After washing in water, the sections were dehydrated in graded alcohols, cleared in xylene and cover-slipped with Permount.

Annexin V histochemical staining
The detection of the early phase of apoptosis staining was performed according to the method developed by us previously, based on binding properties of annexin V to phosphatidylserine (Vermes et al., 1995) (Graupner et al., in preparation). Briefly, at 1 hr 45 min after the induction of global ischemia, the rats were reanesthetized and placed in a stereotaxic frame. A small burr hole was drilled in the skull and 10 μl of biotinylated annexin V in binding buffer (Beckman Coulter) was injected stereotaxically into the right hippocampus (coordinates: 3.7 mm posterior and 3.5 mm lateral to bregma and 3.5 mm below the dura (Shetty et al., 2005) at a rate of 2.5 μL/min over 4 min with a microinfusion pump (Harvard Apparatus). The infusion needle (Hamilton 26 S, 0.46 mm diameter) was kept in situ for an additional 30 min, then removed over 5 min. At 2 hr 45 min after ischemia, rats were sacrificed by formalin perfusion. Brains were postfixed in formalin for 72 hr, cryoprotected and sectioned in the cryostat (10 μm of thickness). To detect biotinylated annexin V bound to phosphatidylserine on the cell membrane of apoptotic cells, brain sections were incubated with Texas red-labeled streptavidin in the blocking serum (Texas Red-Streptavidin; Biomeda Corp.) at room temperature (RT) for 30 min, washed, cover-slipped and observed under a fluorescent microscope (Olympus BX51).

Cell counting
Four animals per group were used for the cell count study. Two slides were used from each brain: one anteriorly and another posteriorly to the injection level (approximately 3.2 mm and 4.2 mm posterior to bregma, respectively). Six visual fields of the cerebral cortex were photographed in each section (three on each side, magnification 200x), which resulted in 12 photographs from the anterior level and 12 from the posterior one for each brain. In total, we took 24 photographs from each brain and 96 per each group (Table 1). Sections were evaluated under an Olympus X51B fluorescent microscope. Cell counts were performed by the experimenters blinded to the study, with the aide of ImageJ software (NIH). Double fluorescence staining with annexin V and cell-specific markers, staining for two distinct apoptotic markers, ans immunodetection of p38/MAPK was performed according to Graupner et al., (in preparation).
Table 1 Table 1
Parameters of Early Apoptotic Cell Counts

TUNEL method
Brain sections were pre-boiled in citric buffer, pH 6.0, for 15 min and labeled with an In Situ Cell Death Detection Kit (Roche). A mixture of FITC-labeled nucleotides and terminal deoxynucleotidyl transferase was applied onto brain sections for 60 min at 37° C in a dark humidified chamber as previously described (Sun et al., 2004; Matchett et al., 2007). Incubation with labeling solution without the enzyme served as negative labeling control.

BDNF immunofluorescence and ELISA
Sections from brains collected at 2 hr 45 min after ischemia were incubated with rabbit antiBDNF antibody diluted 1:100 for 1 hr at RT (Santa Cruz Biotech.), then probed with donkey anti-rabbit FITC-conjugated antibody from Jackson ImmunoResearch Laboratories (1 hr, RT), cover-slipped and observed under fluorescent microscope.

For BDNF ELISA, the rats were transcranially perfused with ice-cold PBS and brain structures including cerebral cortices, were separated, snap frozen, and kept at −80°C until analysis. BDNF ELISA procedure was performed using BDNF Emax ImmunoAssay System (Promega Corporation). Brain tissue was homogenated on ice in lysis buffer (137 mM NaCl, 20 mM Tris-HCl, 1% NP40, 10% glycerol, 1 mM PMSF, 10 μg/ml aprotinin, 1 μg/ml leupeptin, 0.5 mM sodium vanadate) and centrifuged. After measuring the protein concentration with a Dc kit (Bio-Rad), the supernatants (tissue extracts) were diluted in Dulbecco’s PBS and processed according to the manufacturer’s instructions. Briefly, Corning 96 well micro plates were coated with anti-BDNF monoclonal antibodies, and then blocked in a buffer. Two columns of each microplate were designated for the standard curve that used serial dilutions of BDNF standard provided, followed by serially diluted unknowns. Following incubation with polyclonal anti-BDNF antibody and anti-IgY HRP conjugate, enzyme substrate was added and incubated until a blue color formed. The reaction was stopped by the addition of 100 μl of 1N HCl (yellow color formed) and plates read within 30 min in Plate Reader (Bio Tek) at 450 nm. The BDNF concentrations were estimated from the standard curve and expressed as picograms per milligram protein (Gobbo, O'Mara 2004).

Neurobehavioral testing
To evaluate sensorimotor deficits, we used the Garcia score, modified for the evaluation of bilateral deficits (Garcia et al., 1995; Kusaka et al., 2004). Short term memory deficits, corresponding both with hippocampal damage and cortical injuries, were tested in the T-maze by the assessment of spontaneous alternation (Matchett et al., 2007). Briefly, rats were placed in the maze stem and allowed to explore for 1 min. Then 10 trials for spontaneous alternation of maze arms were done over 20 minutes. The results were expressed as percent of spontaneous alternation with respect to 50% reference (Gerlai 2001; Matchett et al., 2007).

Statistical Analysis
All quantitative data are expressed as mean ± SEM. The significance of differences between means was verified by ANOVA followed by Tukey test. For the analysis of cell count results and neurobehavioral scores, a non-parametric Kruskal-Wallis ANOVA was used, followed by Dunn’s test. Mortality rates were analyzed using the chi square test.


Results

Mortality and neurological scores
The mean blood pressure and all blood gas parameters were equivalent in all experimental groups (data not shown). There was a significant increase in glucose level after 4VO both in untreated and preconditioned with HBO, as compared to preischemic levels and in comparison with those levels in the sham group. No significant differences in glucose levels were found between 4VO groups before and after ischemia regardless treated or not. The equivalent postischemic increase in glucose levels in preconditioned vs. non-preconditioned groups suggests that effects of HBO preconditioning were not confounded by hyperglycemia. A mortality of 17 % was recorded in the 4VO no treatment group. Most animals died within the first 24 hr after ischemic insult. As in the sham-operated group, no rat died in the 5HBO group (p <0.05 vs. 4VO), whereas 2 animals (8.69%) died in the 3HBO group. The results of neurological, sensorimotor scoring are presented on Figure 1A as median scores. Sham animals had no neurological deficit throughout the observation period. After global ischemia the neurological score worsened significantly in the 4VO/no treatment group. The reduction of neurological function was smaller, although significant, in the 3HBO and 5HBO groups, with no significant differences between two preconditioned groups. However, unlike for the 5HBO group, the difference between the 3HBO group and the no treatment group reached statistical significance at only 24 hr. At 72 hr a certain degree of recovery was observed in all ischemic groups, although only in preconditioned groups was a full recovery present.
Figure 1 Figure 1
(A) Neurological scoring showed functional deficit in rats after 4VO. Despite a tendency towards recovery, neurological impairment was still present in the untreated group at 72 hr after ischemia. HBO–preconditioned rats show a significant recovery (more ...)

T-maze testing revealed that rats after ischemia had a significant decrease of spontaneous alternation by 64.71% as compared to the sham operated control (Fig. 1B). Sham operated animals and naïve controls (from unrelated study) presented equivalent numbers of spontaneous alternations. 5HBO rats and 3HBO rats showed insignificant decrease in the percentage of spontaneous alternations (by 11.75% and 17.75% vs. sham group, respectively) with no statistical differences between preconditioned groups.

Nissl stain
We found signs of degeneration in cortical neurons and pyramidal cells of CA1 as early as 24 hr after ischemia (Fig. 2A). Moderate shrinkage and darkening of cells were the most abundant changes in both regions. Similar changes were very few in the 5HBO group (Fig. 2B) and much reduced in the 3HBO group (Fig. 2C). At 72 hr after ischemia all CA1 neurons and a large population of cortical neurons were damaged in the 4VO/no treatment group (Fig. 2D), however only several damaged neurons were observed in the HBO preconditioned groups (Figs. 2E and 3F). Injured neurons with twisted axonal processes and cell loss were noted in the CA1 and cerebral cortex at day 7 after ischemia (Fig. 2G). In the 3HBO group, however, relatively numerous dark neurons were observed as compared to the 5HBO group (Fig. 2H) both in the hippocampus and in the cerebral cortex (Fig. 2I).
Figure 2 Figure 2
Representative histological panels show ischemic cell change (arrowheads) in CA1 and in the cerebral cortex at 24 hr, 72 hr and 7 days after global cerebral ischemia (Figs. 2A, 2D and 2G). In the 5HBO preconditioned group, the majority of neurons presented (more ...)
Figure 3 Figure 3
Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) revealed multiple TUNEL positive cells in the cerebral cortex, showing enhanced immunoreactivity for large fragments of cleaved caspase-3 both at 24 and 72 hr after 4VO (Figs. (more ...)

TUNEL and Caspase-3
TUNEL positive cells were observed in the cerebral cortex and in the CA1 of the hippocampus at 24 hr after global ischemia (Fig. 3A). Only a few TUNEL positive cells were present in the cortex in 5HBO and 3HBO preconditioned animals 24 hr after ischemia (Figs. 3B and 3C). At 72 hr, CA1 cells in 4VO untreated global ischemic rats was entirely TUNEL positive (Fig. 3G) and so was a large population of cortical neurons (Fig. 3D). Only a few apoptotic neurons were present in the CA1 and cortex in the 5HBO+4VO group (Figs. 3E and 3H). A decrease of TUNEL staining was also observed in the 3 times HBO preconditioned group although more apoptotic changes were associated with this regimen of preconditioning compared to 5HBO (Figs. 3F and 3I). Immunohistochemistry with monoclonal antibody that recognizes large fragments of activated caspase-3 showed a pattern of immunoreactivity that paralleled TUNEL positive changes. Strong signals for caspase 3 were observed in the no treatment group at 24 hr in the cortex (Fig. 3J) and at 72 hr in the cortex and hippocampus (Figs. 3M and 3P). Five treatments of HBO preconditioning abolished caspase-3 cleavage at 24 hr in the cortex (Fig. 3K) and reduced the number of caspase-3 positive neurons in both structures at 72 hr after ischemia (Figs. 3N and 3R). 3HBO preconditioning did not prevent the appearance of the foci of caspase-3 immunoreactive neurons in the hippocampus (Fig. 3S) and in the cortex (Figs. 3L and 3O).

Apoptotic cell count
Next we wanted to determine if HBO preconditioning protects against early apoptosis (Fig. 4). Histological panels show cells double stained for annexin V and NeuN as well as merged images of those two kinds of stains. Numerous apoptotic cells were present in the cerebral cortex of the no treatment group (Fig. 4B). Only several annexin V- positive cells were observed in the CA1 of the untreated 4VO group (data not shown). Panels 4C and 4D show largely reduced numbers of early apoptotic cells in preconditioned brains. Merging images revealed that a subpopulation of annexin V-expressing cells is not neuronal (Fig. 4J). The results of cell counting are presented in Figure 4M. Around 3% of neurons showed signs of early apoptosis in the sham group. In the ischemic group the overall number of apoptotic cells amounted 32.13% of all cells (7.12-fold increase compared to sham). More than half (16.54%) of those cells were neurons. In the 5HBO group, the number of apoptotic neurons was reduced markedly as compared to the 4VO untreated group even though it remained higher than in the sham group. In the 3HBO preconditioned rats the number of apoptotic cells was 9.98% of all cells and 7.81 % of neurons (significantly higher than the number of positive neurons in sham group); however it was reduced by 52.78% as compared to the number of apoptotic neurons in the 4VO no treatment group. Statistical analysis showed that in 5HBO and 3HBO groups the number of apoptotic cells was significantly different from the number in 4VO no treatment group. Additionally, in all groups, there was a significant increase in the number of apoptotic neurons as compared to the sham group.
Figure 4 Figure 4
The effect of HBO on early apoptosis in neurons (Figs. 4A-4L) and apoptotic cell counts at 2 hr 45 min after global cerebral ischemia (Fig. 4M). A significant increase in the number of annexin V positive cells, predominately neurons, occurred early after (more ...)

Early apoptosis in astrocytes
The results of the cell counts for all early apoptosis suggest that better preservation of neurons in the preconditioned group is associated with improved survival of non-neuronal cells. Therefore, we performed a double fluorescence stain with annexin V and GFAP, astrocytic cell marker. Fig. 4J shows that abundant astrocytes were annexin V positive in non-preconditioned groups. Improved preservation of astrocytes was observed in the preconditioned brains (Figs. 5K and 5L).
Figure 5 Figure 5
The effect of HBO preconditioning on early apoptosis in astrocytes. Annexin V-positive astrocytes were largely absent in the sham-operated group (Fig. 5I). A great number of astrocytes showed a strong annexin V staining after ischemia (Fig. 5J). Partial (more ...)

Double apoptotic stain
Next we tested whether the protection against early apoptosis may contribute to a reduced extent of injury in later post-ischemic stages. In order to do so, we determined whether cells presenting the early apoptotic marker annexin V would progress to positive TUNEL change in the untreated vs. preconditioned groups. In the ischemic group there were few solely annexin V positive cells. On the other hand, especially in the preconditioned brains, solely annexin V positive cells were noted (Fig. 6L).
Figure 6 Figure 6
HBO preconditioning targets progression of apoptosis. Double fluorescence imaging, including annexin V and TUNEL at 16 hr post-ischemia, suggests that cells exteriorizing phosphatidylserine (annexin V-positive) progress to DNA fragmentation in the cerebral (more ...)

Phosphorylated p38
A double fluorescence staining was performed to detect neuronal immunoreactivity (IR) of phosphorylated p38 in the early phase post-ischemia. As shown on Figure 7I, only limited IR of neuronal p-p38 is present in the sham operated animals. In contrast, a strong signal was recorded in rat brains at 2 hr 45 min after ischemia (Fig. 7J). This signal was also observed in the CA1 hippocampal region (Fig. 7J inset). In the 5HBO preconditioned rats the IR of phospho-p38 was remarkably reduced, both in the cerebral cortex and in the CA1 (Fig. 7K). 3HBO preconditioning resulted in only limited suppression of p-p38; still, several foci of p-p38 reactive cells were present in the cerebral cortex and in the hippocampus (Fig. 7L).
Figure 7 Figure 7
HBO preconditioning reduces the activation of p38 in neurons. Very minimal levels of immunoreactivity for phosphorylated p38 (p-p38) were detected in the cerebral cortex and CA1 of sham-operated animals (Fig. 7I). After 4VO there was a tremendous increase (more ...)

BDNF
BDNF immunofluorescence at 2 hr 45 min after 4VO showed a stronger signal in the brains of 5HBO-preconditioned rats (Fig. 8A). BDNF ELISA showed a tendency towards BDNF depletion at 6 hr after global ischemia (Fig. 8B). However, in the HBO preconditioned group, the BDNF level was significantly higher than those in the not preconditioned rats. It was also higher than those in the sham group. These differences disappeared when 24 and 72 hr time point data were analyzed (Figs. 8C and 8D).
Figure 8 Figure 8
BDNF immunofluorescence and ELISA. At 2 hr and 45 min. after 4VO, BDNF immunoreactivity was stronger in the preconditioned group (Fig. 8A). A significantly higher level of cortical BDNF was detected in the 5HBO preconditioned group compared to the no (more ...)

Discussion

There are several major observations of this study. The annexin V stain was positive for phosphatidylserine, providing evidence that apoptosis was occurring in cells in the cerebral cortex as early as 2 hr and 45 minutes after global cerebral ischemia. Cell counts for apoptotic cells revealed significantly less apoptotic cells in the preconditioned groups than in the non-treatment group. No significant difference between the percentages of apoptotic cells in the sham and 5HBO + 4VO groups indicates that HBO pre-conditioning is very effective in reducing early post-ischemic apoptosis. In contrast, around 10% of cortical cells were still apoptotic after 3HBO preconditioning. Although, versus 30% of apoptotic cells in the untreated group, it seems satisfactory, this regimen of preconditioning should be performed only when a longer pretreatment is undesirable. Although not quantified, brain hippocampi also showed higher abundance of early apoptotic cells in the untreated vs. preconditioned rats at 2 hr and 45 min after ischemia (data not shown). The overall abundance of early apoptotic cells in the hippocampi was however smaller than that in the cortex. Keeping in mind that the double apoptotic stain in the hippocampus was present at 16 hr, we assume that intense early apoptotic process in the hippocampus occurred later than 2 hr 45 min. Also TUNEL data seem to support the notion that HBO preconditioning protects against early apoptosis in the hippocampus, what is consistent with the improvement of hippocampus-dependent T-maze test after HBO preconditioning.

According to the manufacturer, the detection of early apoptosis in tissues, either cultured or isolated from humans or animals, requires 30 min incubation with biotinylated Annexin-V before washing and fixation (Beckman). The time between brain injection of annexin and fixation in our in vivo study was 1 hour, likely sufficient for annexin diffusion to remote areas of the brain. Moreover, positive stain with streptavidin conjugated Texas Red in the hemisphere contralateral to the injection strongly suggests effective diffusion of annexin and it’s binding with phosphatidylserine in this brain region.

The classical pattern of injury after global ischemia includes a delayed cell death in the hippocampus and layers II through VI of the cerebral cortex. This suggests that even relatively late intervention is capable of providing brain protection. We observed a very early apoptotic cell change (i.e. presenting phosphatidylserine for macrophage resolving) as early as 2 hr and 45 min after brain insult, which suggests that even quite early intervention (e.g. at 3–6 hr) may be only partly effective as it cannot reduce the amount of the initial damage. We hypothesized that this amount may be critical for the further extent of injury and functional outcome. Therefore we demonstrated the conversion of early apoptotic change to later phase and examined the effect of HBO preconditioning. Indeed, annexin V positive cells did go on to the TUNEL detectible change. Since HBO reduced early apoptosis, thereby, assuming the evidenced conversion of early to late apoptotic change, it reduced the overall extent of delayed brain injury in this mechanism. Interestingly, it also reduced the conversion itself. The latter seems to be particularly promising as it has been postulated that the “inhibition of apoptosis might improve the energy state of the injured cell to such an extent that it may escape necrotic cell death” (Hossmann et al., 2001). The alternative explanation, that there is an occurrence of a delayed phase of apoptosis, is less likely taking into account largely reduced TUNEL signals in the corresponding regions of preconditioned brains at 24 and 72 hr post-ischemia.

Early apoptotic changes appeared earlier in the cerebral cortex than in the CA1. CA1 injury was still limited when annexin V positive cells displayed TUNEL detectible change (Graupner et al., in preparation). Such finding only partially corresponds with an established pattern of selective vulnerability that postulates greater resistance of cerebral cortex than CA1 to ischemia (Chen et al., 1998). Further studies are needed to determine if the early cortical injury may precipitate hippocampal damage. In these settings protection against early cortical damage would trigger a protection against a CA1 injury commonly observed in global ischemic models. Alternatively, the different timing of CA1 vs. cortical changes may occur due to a different quality of reperfusion that, in the cortex, is more efficient and produces immediate phosphatidylserine externalization. In experimental cardiological systems, such externalization has been evidenced as an immediate event after blood flow is restored (Reutelingsperger et al., 2002). In the hippocampus, reperfusion may be impaired, especially assuming permanent occlusion of vertebral arteries (Pulsinelli, Brierley 1979) and therefore injury occurs later, but comprises entire CA1. In addition, the injurious interaction between different brain regions might be vectored by astrocytic damage. Apoptosis in astrocytes has been evidenced after stroke and has received more attention recently (Prunell et al., 2005). Not surprisingly, HBO preconditioning protected also astrocytic cells, suggesting the preservation of their roles in supporting neurons and maintenance of blood brain barrier integrity amongst preconditioning effects (Trendelenburg, Dirnagl 2005).

Immuno-enzymatic and immunofluorescent evidence suggests that HBO pre-conditioning increases BDNF in the cerebral cortex and CA1 early after global ischemia. A previous study reported a decrease in BDNF protein after untreated transient forebrain ischemia (Kokaia et al., 1996). Our findings may indicate that HBO preconditioning decreases early apoptosis via the BDNF pathway. The upstream pathway for BDNF upregulation may include NF-kappaB, for which BDNF gene has a site in a promoter 3 region (Marini et al., 2004). Thus NF-kappaB, which has been shown upregulated by hyperoxia, might induce BDNF especially in the “permanent” 5HBO regimen (Tahepold et al., 2003). We did not investigate BDNF in the 3HBO group since our results suggested that BDNF could have only a limited positive impact in that group. Interestingly, immunofluorescence results suggested neuronal localization of the molecule, which is produced in the brain by glial cells (Leibrock et al., 1989). It is known, however, that BDNF can enter neurons by several mechanisms and neuronal BDNF immunoreactivity has been reported previously (Yanamoto et al., 2000). Although BDNF in our study increased before 3 hr and at 6 hr, Hirata et al. showed genomic change and protein synthesis for neurotrophin receptor that peaked at 12–24 hr post ischemia (Hirata et al., 2007).

We suggest that HBO preconditioning suppressed p-p38/MAPK levels possibly through BDNF overexpression, ascribing a predominantly pro-apoptotic function to p38/MAPK in ischemic neurons. Selective inhibition of p38 activity has been shown to protect neurons against excitotoxic injury (Legos et al., 2002) and focal ischemic injury (Barone et al., 2001; Legos et al., 2001). Although one study showed that p38 is associated with acquired ischemic tolerance, p38 does not seem to be an effector of brain protection, as the same group found benefits of p38 inhibition post ischemia (Sugino et al., 2000a; Sugino et al., 2000b). However, another study found that pretreatment with p38 inhibitor may aggravate ischemic brain injury (Lennmyr et al., 2003). We observe that HBO preconditioning shifts the balance between pro-apoptotic and cell protective functions of p38/MAPK towards cell survival; we propose that HBO preconditioning allows for p38-mediated stimulation of protective signaling pathways while preventing pro-apoptotic, and perhaps excessive p38/MAPK activation in neurons after ischemia. In addition, our results showing suppressed levels of phosphorylated p38/MAPK at less than 3 hr may point to the dominant role of posttranslational modifications as a mediator of early effects of HBO preconditioning.

We have not analyzed likely downstream effectors in our ischemic model, but the involvement of p53 in global ischemic brain injury has lately been confirmed (Endo et al., 2006). Additionally, p38/MAPK mediates cytotoxicity in the endothelial cells (Lee, Lo 2003), and together with ERK1/2, can mediate secretion of MMP-9 in neuronal-astrocytic co-cultures (Wang et al., 2002).

In this present study the proteolytic activation of the caspase-3 was detected at 72 hr in the CA1 degenerating neurons and at 24 hr and 72 hr in the cortical neurons after transient global cerebral ischemia. One study could not find proteolytic activation of the caspase-3 precursor in the cerebral cortex after global ischemia (Chen et al., 1998). The discrepancy may be due to their longer duration of ischemia (15 min) that might trigger predominately necrotic or calpain-mediated cell death. However, consistent with previous studies caspase-3 activation is a process that underlies apoptotic cell death and lasts for days after global ischemia (Li et al., 2005).

According to some previous studies the second wave of caspase activation can occur 12 hr after stroke (Benchoua et al., 2001). We have found no evidence of a new wave of apoptosis that would be assumed if solely annexin V positive cells were observed at 16 hr after untreated ischemia (Graupner et al., in preparation). However, we cannot exclude that together with known late onset of brain inflammation, a new apoptotic wave may appear. Even so, our results seem to indicate that in the preconditioned group the effects of inflammation would be associated with an overall reduced apoptosis.

Our study shows weaker brain protection after short (3HBO) preconditioning and lesser activation of underlying candidate mechanisms. It indicates that longer (e.g. 5HBO) preconditioning should be considered for planned surgeries. However, even shorter HBO preconditioning regimes and exposure to oxygen offer safety advantages over hypoxic preconditioning (Freiberger et al., 2006). Recent studies by Xi and colleagues showed impaired performance after hypoxic preconditioning (Hua et al., 2005). Additionally hypoxic preconditioning procedures resulted in transiently reduced densities of dendritic spines on hippocampal CA1 neurons associated with open-field habituation impairments (Corbett et al., 2006). Our behavioral studies tested performance of animals associated with a function of cerebral cortex (sensory-motor tests) and hippocampus (T-maze) and found improvement in both instances, with no deterioration in neuro scores before ischemia. In this present study we did not calculate neurological scores at day 7 due to a small number of animals investigated at this time point. However in our another study with animals preconditioned and stroked in an identical fashion we found a significant improvement in neurological scores at 7 days as compared to untreated rats with 4VO. In relation to 72 hr time point, there was a further improvement in the preconditioned group which suggests a durable effect of HBO preconditioning (Ostrowski et al., in preparation). Based on our overall data, HBO preconditioning appears as a very effective modality that may be used to achieve durable brain protection through a reduction of the early apoptosis after global cerebral ischemia.

Acknowledgments

This study is partially supported by grants from NIH NS52492 to J. Tang and NS53407, NS45694, and NS43338 to J. Zhang.

Footnotes
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HBOT complementario a Enfermedad de Parkinson

La Oxigenación Hiperbárica ha demostrado su efectividad para reducir los síntomas del Mal de Parkinson ya que presenta mejoras significativas en rigidez, postura, expresión facial, lentitud para los movimientos, modo de andar, sueño y movilidad.

La Oxigenación Hiperbárica administrada a los pacientes con el Mal de Parkinson complicado, aumenta la producción Mitocondrial del Adenosin Trifosfato y la Fosfocreatinina dando como resultado un aumento en la energía neuronal, de tal manera que compensa la enfermedad ó resuelve sus complicaciones.

El mecanismo de acción de las terapias de Oxigenación Hiperbárica está basado en el hecho de que los pacientes con esta patología tienen mayor actividad en la fracción Mitocondrial de la Superóxido Dismutasa (SOD) en algunas regiones cerebrales entre las cuales se encuentra principalmente la Sustancia Negra.
La Oxigenación Hiperbárica favorece la producción de las Enzimas Detoxificadoras, especialmente de la Superóxido Dismutasa (SOD) y de la Catalasa.

Esto explica las ventajas clínicas que se pueden obtener con ésta terapia administrada en el momento adecuado, en patologías neurológicas tales como el Mal de Parkinson.
La Oxigenación Hiperbárica no solo mejora los síntomas clásicos de la enfermedad de Parkinson (expresión, expresión-facial, capacidad de escritura, habla y en sus movimientos), sino también en los desórdenes autonómicos y en el estado de la depresión.
os pacientes con Mal de Parkinson presentan deficiencia de Glutation que es un químico esencial para el cerebro ya que juega un rol muy importante en el tratamiento de este mal. El Glutation es un poderoso antioxidante que ayuda a prevenir el daño que ocasionan los radicales libres a los tejidos del cerebro.

Las terapias de Oxigenación Hiperbárica y una nutrición balanceada son muy útiles para la producción de este antioxidante.

Además la Oxigenación Hiperbárica aumenta la eficacia de los medicamentos que controlan el mal.


Mecanismos de acción de la Oxigenación Hiperbárica:

* Combate la hipoxia.
* Mejora la microcirculación.
* Por su efecto vasoconstrictor combate el edema cerebral.
* Preserva el tejido parcialmente dañado y previene el futuro progreso de los efectos secundarios de las lesiones cerebrales.
* Mejora el metabolismo cerebral (convierte el mecanismo anaerobio en aerobio).
* Apoyo inmediato al tejido hipóxico ó mal perfundido permitiendo la normalización bioenergética.
* Activa las neuronas dormidas en la zona de penumbra isquémica.
* Atenúa la lesión por reperfusión posterior a un evento isquémico.
* Antiagregante plaquetario y antiserotonínico.
* Incrementa la capacidad del ejercicio físico y mental.

¿La exposición hiperbárica de oxígeno afecta a la marca deportiva en ejercicios de alta-intensidad y corta duración?

Noticias cientificas
Artículo de marzo de 2008: ¿La exposición hiperbárica de oxígeno afecta a la marca deportiva en ejercicios de alta-intensidad y corta duración?

Resumen en español: La exposición hiperbárica de oxígeno (HBO) consiste en respirar 100% oxígeno bajo unas condiciones de elevada presión y se usa para incrementar la cantidad de fracción de oxígeno en el plasma de la sangre arterial. El objetivo de este estudio era determinar los efectos de una exposición aguda a oxígeno hiperbárico en la respuesta de diferentes variables fisiológicas y la marca deportiva a un ejercicio máximo, de intensidad elevada y corta duración en las extremidades inferiores y superiores. El estudio fue realizado en 2 experimentos separados, en doble ciego y realizado de forma aleatoria. En el experimento 1, 9 sujetos corrieron en un tapiz rodante a una velocidad de 268 m·min-1 con una pendiente predeterminada. En el experimento 2, 9 sujetos diferentes realizaron una prensa de banca repetitiva. Los dos protocolos eran diseñados para producir la fatiga en 1-2 minutos. Dentro de cada experimento, los sujetos recibieron 1 hora de exposición a 100% O2 inspirando, a 202.6 kPa (2.0 atmósferas de presión absoluta [ATA] o 1 hora de exposición de aire ambiente inspirando a 11.5 kPa (1.2 ATA) antes del ejercicio. No se encontraron diferencias significativas (p > 0.05) en la concentración de lactato, pico de la frecuencia cardíaca, la percepción del esfuerzo, o la marca deportiva determinada como el tiempo de agotamiento en el tapiz rodante o el número de repeticiones realizadas. A diferencia de otros métodos, la exposición hiperbárica de oxígeno aguda no parece tener ningún efecto en carreras de alta intensidad o en el número de repeticiones realizadas.


Aplicaciones prácticas: A diferencia de otros métodos como el dopaje sanguíneo o el entrenamiento en altitud, los cuales pueden incrementar el número de glóbulos rojos, la exposición hiperbárica de oxígeno aguda produce una elevación aguda en el contenido de la fracción de oxígeno en el plasma y en los tejidos. Sin embargo, este efecto podría tener una duración corta una vez que el individuo es expuesto a un ambiente o condiciones de presión atmosférica y concentración de oxígeno normales. Los resultados derivados de este estudio indican que la exposición de 100% de O2 en una situación hiperbárica no produce ningún efecto ergogénico en la marca deportiva en un esfuerzo máximo, con una duración de al menos 1-2 minutos.

Resumen original: Hyperbaric oxygen (HBO) exposure involves the breathing of 100% oxygen under conditions of elevated atmospheric pressure and is used to increase the oxygen content of the plasma fraction of arterial blood. The purpose of this study was to determine the effects of acute HBO exposure on selected physiological responses and performance in response to maximal lower extremity or upper extremity short-term, high-intensity exercise. The study was performed with 2 separate experiments incorporating double-blind and randomized protocols. In experiment 1, 9 subjects ran on a treadmill at a speed of 268 m·min-1 with a predetermined grade. In experiment 2, 9 different subjects performed a repetitive bench exercise. Both exercise protocols were designed to induce fatigue within 1-2 minutes. Within each experiment, subjects received either a 1-hour HBO exposure inspiring 100% O2 at 202.6 kPa (2.0 atmospheres absolute pressure [ATA] or a 1-hour sham exposure inspiring ambient air at 11.5 kPa (1.2 ATA) before exercise. No significant differences (p > 0.05) were observed in post-exercise blood lactate concentrations, peak heart rate, ratings of perceived exertion, or performance as determined by treadmill running time or number of complete lifts. Unlike other methods that elevated oxygen content of the blood, acute HBO exposure appears to have no significant effect on subsequent high-intensity running or lifting performance.

Rozenek R, Fobel BF, Banks JC, Russo AC, Lacourse MG, and Strauss MB. Does hyperbaric oxygen exposure affect high-intensity, short duration exercise performance? Journal of Strength and Conditioning Research 21(4):1037-1041, 2008.

Dolor Muscular y HBOT

Agujetas
D
Se consideran un dolor muscular localizado debido a la práctica de ejercicio

Las agujetas (nombre médico mialgia diferida) es el nombre coloquial de un dolor muscular llamado "Dolor muscular de aparición tardía" (en inglés DOMS: Delayed Onset Muscular Soreness) acompañado de una inflamación muscular.[1] [2] Aparece como un dolor localizado después de un período de ejercicio intenso tras un período carente de ejercicio.[3] Su síntoma es un dolor intenso y localizado similar al de pequeñas agujas (de ahí el nombre) y suponen una disminución de la movilidad y la flexibilidad durante un periodo entre uno (24 h) y cinco días, dependiendo de la actividad y del historial previo de carencia deportiva. Existen numerosas teorías sobre el origen de las agujetas.[1]
Contenido
[ocultar]

* Fundamento de la mialgia diferida

La mialgia diferida (agujetas) aparece siempre en la práctica de un ejercicio en la que existe una contracción muscular excéntrica (contraria a la gravedad - un ejemplo puede ser cuando se corre cuesta arriba). Las investigaciones realizadas muestran que se produce igualmente en los músculos de animales que en los humanos.[1] El dolor proporciona sensación de rigidez al atleta y afecta tanto a atletas expertos como novatos, el factor importante es la "familiaridad" con el ejercicio realizado.[4] La intensidad de la mialgia es mayor cuanto más intenso ha sido el ejercicio realizado y menos habitual es en la rutina deportiva, aunque sobre este punto existe todavía una discusión en la comunidad científica.[5] Existen algunas teorías acerca del fundamento de la mialgia diferida:

* Microrrotura de fibras musculares - esta teoría es la más aceptada por la comunidad científica,[6] menciona que el dolor muscular y la inflamación se producen debido al número de microfibras rotas durante la práctica del ejercicio.
* Temperatura incrementada localmente en los músculos - Esta teoría menciona que durante la práctica del ejercicio el músculo se calienta y en algunas zonas se producen "microlesiones". Posee cierta similitud con la teoría de las microrroturas musculares y la comunidad científica está pendiente de más investigaciones al respecto.
* Acumulación del ácido láctico - esta teoría, ya en desuso, acaba mencionando que el ácido láctico resultante de la actividad metabólica en las células musculares acaba "cristalizando" (de ahí viene su nombre) siendo esta la causa final del dolor muscular debido a la supuesta presencia de estos cristales intersticiales en el músculo.[7]

Existen otras teorías que aportan explicaciones a algunos efectos de la mialgia, quedando sin explicar otros.

Microrrotura de fibras musculares
La teoría de la microrrotura es clásica ya que en el año 1902 se formuló por primera vez,[8] en ella se menciona que la mialgia aparece tras la práctica deportiva se explica mediante alguna literatura científica como una rotura de fibras musculares en su mínima expresión, técnicamente es la rotura de los sarcómeros musculares.[9] Lo que acaba produciendo un efecto de inflamación ligero del músculo afectado.[10] Este dolor se debe a que la fibra muscular es débil y no es capaz de sostener el nivel de ejercicio, probablemente porque se está desentrenado y la fibra no es capaz de aguantarlo. Los patrones de rotura dentro del músculo son completamente aleatorios.[11] Existe alguna evidencia científica que menciona una mayor cantidad de microroturas en los músculos de contracción rápida.[12] [11] Esta teoría parece ser la más aceptada por la comunidad científica y se han realizado numerosos estudios en deportistas.[13]

Las zonas más afectadas por este dolor son las uniones musculares y los tendones cerca de las articulaciones, esto se debe a que la zona musculotendinosa es donde existen más fibras musculares débiles y más tensión. Existe un segundo supuesto: los receptores del dolor (nociceptores) se encuentran en mayor cantidad en estas regiones.[13] El dolor muscular suele tener un periodo que oscila entre los 5 y 7 días con un pico de dolor que se muestra a los 1-3 días tras el ejercicio. Por ejemplo, el dolor y la relajación de los músculos no contribuye a la pérdida de fuerza que aparece en los días de recuperación, no existen evidencias de una inhibición neuronal sobre los músculos[14] y una desactivación en las unidades motoras[15] El dolor y la debilidad muscular se deben prinicipalmente a los procesos inflamatorios más que al daño micromuscular producido.[16] Las investigaciones realizadas se han fundamentado en el desbalance sobre la homeostasis del calcio en los tejidos musculares debido a la microroturas musculares.[17]

Aumento de la temperatura
Durante un ejercicio intenso las células musculares pueden alcanzar temperaturas entre los 38º y los 48º, lo que supone una muerte celular o necrosis. Este proceso genera una desorganización estructural en los músculos que acaba generando un dolor generalizado en ciertos músculos.[18] Esta teoría se ha convertido en una derivación de la de microrotura de las fibras musculares, ya que puede considerarse como una causa más de la microrotura.

Acumulación de ácido láctico

La teoría fue establecida por primera vez por Assmussen en el año 1956[7] y desde entonces la teoría ha ido siendo cada vez más abandonada por la comunidad científica. En condiciones de anoxia (falta de oxígeno) como la que ocurre en las células musculares durante un ejercicio intenso el metabolismo cambia y las células fermentan los nutrientes para conseguir energía. La fermentación produce mucha menos energía que el metabolismo normal, que degrada la glucosa a dos ácidos pirúvicos y este se degrada completamente por otras rutas metabólicas. Sin embargo, en la fermentación el ácido pirúvico se transforma en ácido láctico que cristaliza en el músculo. El dolor producido, por tanto, sería el resultado de la acidez incrementada captada por los nervios y por las microrroturas del músculo debido a los cristales.[19]

Según mencionan algunos autores, esta teoría tiene pocos fundamentos, la observación muscular mediante biopsias musculares no ha podido mostrar la aparición de tales cristales. Tras formarse los cristales de ácido láctico muchos se degradan y una pequeña parte se recombina con otras sustancias para proporcionar moléculas energéticas (glucosa). Otra evidencia que niega tal cristalización es que el ácido láctico llega a cristalizar a temperaturas inferiores a -5ºC, cosa que hace que esta teoría pase a ser una "leyenda urbana" establecida por la transmisión de deportista a deportista sin llegar a un fundamento científico claro.

Espasmo muscular

Introducida en el año 1961 por Dvries,[20] esta teoría propone que el dolor sea resultado de pequeñas descargas eléctricas debido a la fatiga del músculo. Durante un periodo de actividad intensa las contracciones musculares reducen el flujo sanguíneo provocando daños a las células (isquemia) lo que produce un estímulo en las terminaciones nerviosas que vuelven a contraer la fibra muscular, con lo que se repite el ciclo. El aumento de la actividad eléctrica produce, además de la excitación de los nervios una gran fatiga muscular por la falta de flujo sanguíneo. La teoría ha sido criticada por algunos estudiosos de la fisiología y hoy en día se pone en duda.[21]

Tratamiento de la mialgia diferida

Se han investigado numerosos tratamientos contra la mialgia diferida tanto en situaciones previas como posteriores al ejercicio. Estas intervenciones se pueden clasificar en tres amplias categorías:[22]

* Farmacológicas que emplean tratamientos de productos no-esteroides y anti-inflamatorios (denominados en inglés: nonsteroidal anti-inflammatory drugs - NSAIDs). Estos métodos se centran básicamente en aliviar el dolor causado por las agujetas. No obstante los resultados acerca de sus beneficios son muy confusos, ya que existe abundante literatura que demuestra tanto sus efectos beneficiosos como los neutros.[16] Algunos medicamentos han sido ligeramente beneficiosos, como el ibuprofeno[23] [24] o el naproxeno.[25] Sin embargo hay estudios que mencionan el efecto nulo de la aspirina (a pesar de la creencia popular).[26]
* Terapéuticos que emplean modalidades físicas: diversas modalidades de masaje, ejercicios físicos específicos,[27] crioterapia,[28] ultrasonidos e incluso estimulación eléctrica.[29] Respecto a algunas terapias como la oxigenación hiperbárica (HBO, una terapia consistente en la inhalación de Oxígeno (O2) a altas dosis) se está produciendo un debate científico en la actualidad.[30]
* Dietéticas que emplean suplementos nutricionales tales como las isoflavonas (como pueden ser las isoflavonas de soja) y algunos aceites procedentes de pescados que se han mostrado eficaces en el tratamiento.[31] Se necesita todavía un "corpus" de investigación en esta área.

Prevención

No existe un método claro para prevenir y tratar las agujetas a pesar de las numerosas investigaciones.[16] Sin embargo se ha demostrado que los estiramientos musculares previos a la realización del ejercio así como posteriores disminuyen la intensidad del dolor. También tiene efectos positivos sacudirse los músculos durante la realización del ejercicio físico (favorece la circulación sanguínea) y tomarse una ducha caliente al concluirlo.[32] [33] Es conveniente un calentamiento previo así como el aumento progresivo del nivel de entrenamiento, empezando por ejercicios suaves hasta llegar a los más intensos,[34] de este modo las fibras musculares se preparan para una situación de esfuerzo.

Algunos suplementos dietéticos que parecen tener algún efecto en la mialgia diferida son la árnica, de origen homeopático;[35] la ubiquinona (coenzima-Q); y la L-carnitina, en ciertos trabajos científicos sobre corredores de maratón.[36]

Postratamiento
Se ha realizado una exhaustiva investigación acerca de como tratar las agujetas una vez se producen. Uno de los métodos más empleados en la medicina deportiva es el masaje muscular.[37] [38] El uso de antioxidantes (vitamina C y E) no ha dado resultados positivos para eliminar sus efectos.[39]

Una idea muy extendida y popular es que el consumo de agua con bicarbonato sódico o azúcar puede utilizarse para combatir las agujetas. Este remedio casero es el resultado de la aceptación masiva de la teoría referente al ácido láctico. Puesto que esta teoría está prácticamente descartada, este método probablemente no evita ni cura las agujetas ni sus síntomas, pero puede provocar basicidad y problemas gástricos. Por lo tanto no debe seguirse un tratamiento de este tipo. No obstante, podemos encontrar un pequeño alivio en la aplicación de frío. En caso de dolor muy intenso se puede tomar ibuprofeno, que aúna propiedades analgésicas y anti-inflamatorias.

Referencias

1. ↑ a b c "Acute inflammation: the underlying mechanism in delayed onset muscle soreness?", S. Lucille; Medicine & Science in Sports & Exercise. 23(5):542-551, May 1991
2. ↑ "Exercise-induced muscle damage and potential mechanisms for the repeated bout effect", MCHUGH, M.P., D.A.J. CONNOLLY, R.G. ESTON, AND G.W. GLEIM. Sports Med. 27:158–170. 1999.
3. ↑ "Abraham, WM: "Factors in delayed muscle soreness". Med Sci Sports Exerc 9:11
4. ↑ "Delayed Onset Muscle Soreness: Treatment Strategies and Performance Factors", Cheung, Karoline; Sports Medicine. 33(2):145-164, 2003
5. ↑ "Delayed-onset muscle soreness does not reflect the magnitude of eccentric exercise-induced muscle damage"; Kazunori Nosaka; Scandinavian Journal of Medicine & Science in Sports, Volume 12 Issue 6 Page 337-346, December 2002
6. ↑ "Morphologic and Mechanical Basis of Delayed-Onset Muscle Soreness", Richard L. Lieber, PhD and Jan Fridén, MD, PhD ; J Am Acad Orthop Surg, Vol 10, No 1, January/February 2002, 67-73.
7. ↑ a b "Observations on experimental muscle soreness". Asmussen E:, Acta Rheum Scand 1956; 2:109-116
8. ↑ "Ergographic studies in muscular soreness". Hough, T. (1902). American Journal of Physiology, 2, 76-92.
9. ↑ "Materials fatigue initiates eccentric contractioninduced injury in rat soleus muscle", WARREN, G.L., D.A. HAYES, D.A. LOWE, B.M. PRIOR, AND R.B. ARMSTRONG. J. Physiol. 464:477–489. 1993.
10. ↑ "Haematological and acute-phase responses associated with delayed-onset muscle soreness in humans"; GLEESON, M., J. ALMEY, S. BROOKS, R. CAVE, A. LEWIS, AND H. GRIFFITHS. Eur. J. Appl. Physiol. 71:137–142. 1995.
11. ↑ a b "Muscle damage induced by eccentric contractions of 25% strain", Lieber, R.L., And J. Fride´N, J. Appl. Physiol. 70:2498–2507. 1991
12. ↑ "Changes in human skeletal muscle induced by longterm eccentric exercise", Fridén, J. . Cell Tissue Res. 236:365–372. 1984.
13. ↑ a b "Exercise-induced muscle damage and potential mechanisms for the repeated bout effect", Mchugh, M.P., D.A.J. Connolly, R.G. Eston, And G.W. Gleim. Sports Med. 27:158–170. 1999.
14. ↑ . "Electromyographic analysis of exercise resulting in symptoms of muscle damage". Mchugh, M.P., D.A.J. Connolly, R.G. Eston, And G.W. Gleim, J. Sports Sci. 8:163–172. 2000.
15. ↑ . "Effect of ketoprofen on muscle function and EMG after eccentric exercise". Sayers, S.P., C.A. Knight, P.M. Clarkson, E.H. Van Wegen, And G. Kamen. Med. Sci. Sports Exerc., 33:702–710. 2001.
16. ↑ a b c "Treatment and Prevention of Delayed Onset Muscle Soreness", DECLAN A.J.; Journal of Strength and Conditioning Research, 2003, 17(1), 197–208
17. ↑ "Hydrogen peroxide disrupts calcium release from the sarcoplasmic reticulum of rat skeletal muscle fibers". Brotto, M., And T.M. Nosek, J. Appl. Physiol. 81:731–737. 1996.
18. ↑ "Response of the body to injury: Inflammation and repair. In: Pathophysiology: Clinical Concepts of Disease Processes". ABRAMS, G.D. S.A. Price and L.M. Wilson, eds. St. Louis, MO: Mosby, 1997. pp. 38–58.
19. ↑ "Traumatología y Medicina Deportiva: Bases de la Medicina del Deporte", Rafael Ballesteros Massó, Publicado en 2002, Thomson Learning Ibero
20. ↑ "Prevention of muscular stress after exercise". DeVries, H.A. Research Quarterly, 32, 177. (1961).
21. ↑ "Factors in delayed onset muscular soreness of man", Bobbert, M.F., Hollander A.P. & Huijing P.A. (1986). Medicine and Science in Sports and Exercise, 18(1), 75-81.
22. ↑ "Various Treatment Techniques on Signs and Symptoms of Delayed Onset Muscle Soreness", Gulick DT, Kimura IF, Sitler M, Paolone A, Kelly JD.; J Athl Train. 1996 Apr;31(2):145-152
23. ↑ "Effects of ibuprofen on exercise-induced muscle soreness and indices of muscle damage", Donnelly, A.E., R.J. Maughan, And P.H. Whiting. . Br. J. Sports Med. 24:191–195. 1990.
24. ↑ "Effect of ibuprofen use on muscle soreness, damage, and performance: A preliminary study", Hasson, S.M., J.C. Daniels, J.G. Divine, B.R. Niebuhr, S. Richmond, P.G. Stein, And J.H. Williams. . Med. Sci. Sports Exerc. 25:9–17. 1993.
25. ↑ "Efficacy of naproxen sodium for exercise-induced dysfunction muscle injury and soreness"; Dudley, G.A., J. Czerkawski, A.Meinrod, G.Gillis, A. Baldwin, And M. Scarpone. . Clin. J. Sport Med. 7:3–10. 1997.
26. ↑ "Effects of aspirin on delayed muscle soreness", Francis, K.T., And T. Hoobler. J. Sports Med. 27:333–337. 1987.
27. ↑ "Intermittent pneumatic compression effect on eccentric exercise-induced swelling, stiffness and strength loss", Chleboun, G.S., J.N. Howell, H.L. Baker, T.N. Ballard, J.L. Graham, H.L. Hallman, L.E. Perkins, J.H. Schauss, And R.R. Conaster. . Arch. Phys. Med. Rehabil. 76:744–749. 1995.
28. ↑ "Effects of cold water immersion on the symptoms of exercise-induced muscle damage", Eston, R., And D. Peters. J. Sports Sci. 17:231–238. 1999.
29. ↑ "Electroestimulación: Entrenamiento y periodización", Manuel Pombo Fernández, Publicado en 2004; ed. Paidotribo; ISBN 84-8019-776-5
30. ↑ "Hyperbaric oxygen therapy does not affect recovery from delayed onset muscle soreness". Mekjavic, I.B., J.A. Extner, P.A. Tesch, And O. Eiken. Med. Sci. Sports Exerc. 3:558–563. 2000.
31. ↑ "The effects of fish oil and isoflavones on delayed onset muscle soreness", Jon Lenn; Medicine & Science in Sports & Exercise. 34(10):1605-1613, October 2002.
32. ↑ "La guía completa de los estiramientos", Christopher M. Norris; Publicado en 2001, Ed.
33. ↑ "The effects of static stretching and warm-up on prevention of delayed-onset muscle soreness.", High DM, Howley ET, Franks BD; Res Q Exerc Sport. 1989 Dec;60(4):357-61.
34. ↑ "Science of Flexibility", Michael J. Alter; 2004, Ed. Human Kinetics
35. ↑ "Homoeopathic Arnica and Rhus toxicodendron for delayed onset muscle soreness A pilot for a randomized, double-blind, placebo-controlled trial"; N. Jawara, British Homoeopathic journal; Volume 86, Issue 1, January 1997, Pages 10-15
36. ↑ TVEITEN, D., S. BRUSET, C.F. BORCHGREVINK, AND J. NORSETH. "Effect of Arnica D 30 during hard physical exertion: A doubleblind randomized trial during the 1995 Oslo Marathon. Complement. Ther. Med. 6:71–74. 1998.correr a sprint durante 20 sg
37. ↑ "Does post-exercise massage treatment reduce delayed onset muscle soreness? A systematic review". E Ernst; British Journal of Sports Medicine, Vol 32, Issue 3 212-214; 1998
38. ↑ "The effects of massage on delayed onset muscle soreness", J E Hilbert, G A Sforzo, T Swensen; J Sports Med 2003;37:72-75
39. ↑ "An effect of ascorbic acid on delayed-onset muscle soreness Pain", Kaminski, M & Boal, R. (1992); 50(3), 327-321.