[Effect of combination therapy with hypothermia, magnesium and tirilazad in an experimental model of diffuse cerebral ischemia]. / Efecto de la hipotermia combinada con magnesio y tirilazad en un modelo experimental de isquemia cerebral difusa*

OBJECTIVE: To determine the grade of neuroprotection of combined treatment with moderate hypothermia, tirilazad and magnesium sulfate. Cerebral ischemia is one of the problems of great interest at present, with limited therapeutic measures. Hypothermia, one of the more efficient measures, together with neuroprotector pharmaceuticals, could be a valid alternative. DESIGN: Experimental study with a control group and two levels of application of therapeutic measures. CONTEXT: Experimental laboratory of the Medicine Faculty. PARTICIPANTS AND METHOD: Twenty-eight Wistar rats underwent global cerebral ischemia of 10 minutes duration by the combination of bilateral carotid clamping and controlled hypotension (mean arterial pressure: 45 mmHg). Three groups were used: group I, normothermia maintenance; group II, moderate hypothermia (32-33 degrees C) for 2 hours; group III, hypothermia and administration of tirilazad mesylate and magnesium sulfate during the reperfusion and two hours after ischemia. The animals were sacrificed at 7 days and, after processing the tissue, the neurons preserved in layer CA1 of the hippocampus were counted. RESULTS: There is a significantly greater neuronal preservation in group III with regard to group I (55.4 +/- 5.1 versus 38.7 +/- 8.8, p < 0.0001). If we compare groups II and III, significant differences are only obtained on the right side and in the hippocampus considered globally, favoring the group with hypothermia and drugs. When groups I and II are compared there are no significant differences. CONCLUSIONS: Association of moderate hypothermia, magnesium sulfate and tirilazad mesylate in the experimental model of transitory global ischemia used is confirmed as an effective neuroprotector measure, surpassing the degree of neuronal preservation of hypothermia alone.

Efecto de la hipotermia combinada con magnesio y tirilazad en un modelo experimental de isquemia cerebral difusa / Effect of combination therapy with hypothermia, magnesium and tirilazad in an experimental model of diffuse cerebral ischemia

Objetivo. Valorar el grado de neuroprotección combinando hipotermia con magnesio y tirilazad en la isquemia cerebral global. La isquemia cerebral es uno de los problemas de mayor interés en la actualidad con unas medidas terapéuticas limitadas. La utilización de la hipotermia, una de las más eficaces, junto con los fármacos neuroprotectores puede ser una alternativa válida. Diseño. Estudio experimental con grupo control y dos niveles de aplicación de medidas terapéuticas. Ámbito. Laboratorio experimental de la Facultad de Medicina. Participantes y método. Veintiocho ratas Wistar sufrieron isquemia cerebral global de 10 minutos de duración mediante la combinación del clampaje carotídeo bilateral y la hipotensión controlada (presión arterial media: 45 mmHg). Se utilizaron tres grupos: grupo I, mantenimiento de normotermia; grupo II, hipotermia moderada (32-33 ºC) durante dos horas; grupo III, hipotermia y administración de mesilato de tirilazad y sulfato de magnesio durante la reperfusión y a las dos horas de realizada la isquemia. A los 7 días se sacrificaban los animales y tras el procesamiento del tejido se cuantificaban las neuronas preservadas en la capa CA1 del hipocampo. Resultados. Existe mayor preservación neuronal de forma significativa en el grupo III con respecto al grupo I (55,4 ± 5,1 frente a 38,7 ± 8,8, p < 0,0001). Si comparamos los grupos II y III, sólo se obtienen diferencias significativas en el lado derecho y en el hipocampo considerado globalmente, a favor del grupo de hipotermia más fármacos. Comparados los grupos I y II no existen diferencias significativas. Conclusiones. La asociación de hipotermia moderada, sulfato de magnesio y mesilato de tirilazad en el modelo experimental utilizado de isquemia global transitoria se confirma como una medida neuroprotectora eficaz, superando el grado de preservación neuronal de la hipotermia aislada

Objective. To determine the grade of neuroprotection of combined treatment with moderate hypothermia, tirilazad and magnesium sulfate. Cerebral ischemia is one of the problems of great interest at present, with limited therapeutic measures. Hypothermia, one of the more efficient measures, together with neuroprotector pharmaceuticals, could be a valid alternative. Design. Experimental study with a control group and two levels of application of therapeutic measures. Context. Experimental laboratory of the Medicine Faculty. Participants and method. Twenty-eight Wistar rats underwent global cerebral ischemia of 10 minutes duration by the combination of bilateral carotid clamping and controlled hypotension (mean arterial pressure: 45 mmHg). Three groups were used: group I, normothermia maintenance; group II, moderate hypothermia (32-33 ºC) for 2 hours; group III, hypothermia and administration of tirilazad mesylate and magnesium sulfate during the reperfusion and two hours after ischemia. The animals were sacrificed at 7 days and, after processing the tissue, the neurons preserved in layer CA1 of the hippocampus were counted. Results. There is a significantly greater neuronal preservation in group III with regard to group I (55.4 ± 5.1 versus 38.7 ± 8.8, p < 0.0001). If we compare groups II and III, significant differences are only obtained on the right side and in the hippocampus considered globally, favoring the group with hypothermia and drugs. When groups I and II are compared there are no significant differences. Conclusions. Association of moderate hypothermia, magnesium sulfate and tirilazad mesylate in the experimental model of transitory global ischemia used is confirmed as an effective neuroprotector measure, surpassing the degree of neuronal preservation of hypothermia alone