Delayed selective cerebral hypothermia decreases infarct volume after reperfused stroke in baboons

Hypothermia is known to provide neuroprotection from focal ischemia. However, lethal cardiovascular complications resulting from total body cooling have greatly restricted hypothermia as a therapy for stroke. This study determined whether selective cerebral cooling induced after reversible cerebral artery occlusion would decrease the infarct volume.

Under general anesthesia, 8 baboons were subjected to 1-hour simultaneous occlusion of the left internal carotid artery and anterior cerebral arteries by transorbital surgical approach. Four animals were treated with selective cerebral hypothermia to 25°C, initiated 2.5 hours after placement of cerebral artery clips. Selective cerebral hypothermia was achieved, after heparinization, by continuous withdrawal of femoral arterial blood into an extracorporeal closed-circuit pump system, cooling by water bath and perfusion into the right internal carotid artery. Pump flow was adjusted to maintain right internal carotid artery pressure near systemic blood pressure. Cerebral cortical temperature was maintained below 27°C for 12 hours, whereas systemic temperature was preserved near normal by convective air mattresses and warm water blankets. Four control animals were maintained at 36°C. Blood pressure, pH, and blood gases were maintained at normal values for both groups. Forty-eight to 72 hours after cerebral artery occlusion, magnetic resonance imaging brain scans were obtained and infarct volume measured.

Normothermic baboons had infarction of 35.4±4.4% (mean±SD) of the left cerebral hemisphere compared with 0.5±1% for baboons treated with cerebral hypothermia (P<0.01). In brain-cooled animals, esophageal temperature was maintained greater than 34°C, despite cerebral temperature less than 27°C.

Selective brain cooling initiated 2.5 hours after onset of focal ischemia resulted in marked reduction in infarct volume, without cardiovascular derangement.