Cerebral hypothermia during and immediately after hypoxia-ischemia critically modulates outcome. However, the effect of delayed, 'rescue' cooling remains equivocal. Fetal sheep (GA, 119 to 126 d) were instrumented with brachial artery and sagittal sinus catheters, bilateral carotid ultrasonic flow probes and inflatable occluders, esophageal and extradural (ED) thermistors, and parietal EEG and impedance electrodes. A silastic 'cooling coil' was wrapped over the head, with the ends exteriorized to allow cooled water to be circulated from a refrigerated waterbath over the fetal head. Three days after surgery cerebral ischemia was induced by carotid occlusion for 30 min. After 90 min reperfusion, fetuses were randomized to cooling or sham cooling for 72 h. After 48 h recovery the brains were perfusion fixed.
Sham cooled fetuses developed delayed intense seizure activity, from 6 to 9 h, peaking at 12 h, and secondary cytotoxic edema, peaking after 36 h. In the cooled group, ED temperature fell by 5 to 10°C initially, and the esophageal by 1.5 to 3°C. In the second and third days ED temperature was 3 to 5°C below baseline. Cooling was associated with reduced seizure intensity, greater residual EEG activity on day 5 (-5.2±4.9 vs-15.5±4.1 dB, p<0.01) and suppression of cortical secondary cytotoxic edema (p<0.001) while histology showed reduced cortical infarction (p<0.001). The degree of cortical cooling was linearly correlated with both suppression of cytotoxic edema (r=0.81) and residual EEG activity (r=0.59), as well as with reduction in histological damage. Measurements of cerebral oxygen consumption indicated that ED cooling below 34°C suppressed cerebral oxidative metabolism. These data suggest that moderate selective cerebral hypothermia, continued throughout the vulnerable period, can markedly attenuate secondary damage from perinatal hypoxia-ischemia.
