[Effect of combination therapy with hypothermia, magnesium and tirilazad in an experimental model of diffuse cerebral ischemia].
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.


METHODS
Experimental study with a control group and two levels of application of therapeutic measures.


BACKGROUND
Experimental laboratory of the Medicine Faculty.


METHODS
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.
Sánchez-Casado
M
M
Unidad de Cuidados Intensivos, Hospital Nuestra Señora del Prado, Talavera de la Reina, Toledo, España. marcel55@terra.es
Sánchez-Ledesma
M J
MJ
Gonçalves-Estella
J M
JM
Abad-Hernández
M M
MM
García-March
G
G
Broseta-Rodrigo
J
J
D000818:Animals; D002545:Brain Ischemia / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D007036:Hypothermia, Induced; D008274:Magnesium / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011281:Pregnatrienes / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D018696:Neuroprotective Agents; D011281:Pregnatrienes; D008274:Magnesium; C053355:tirilazad