Immediate or delayed mild hypothermia prevents focal cerebral infarction

Abstract

The protective effect of mild hypothermia was studied in rodent models of both permanent and transient focal cerebral ischemia. In Expt. 1, Wistar rats were exposed to 6 h permanent ischemia by bilateral occlusion of both common carotid arteries and right middle cerebral artery. In Expt. 2, animals were exposed to 3 h transient ischemia followed by 21 h reperfusion, and in Expt. 3, 3 h transient ischemia was followed by 69 h of reperfusion. Expt. 4 used 3 h transient ischemia followed by 3 h reperfusion. In Expt. 1, animals maintained at 37°C rectal (normothermia) suffered a mean infarct volume (±S.D.) of 142 ± 44 mm 3 ( n = 6), which was reduced for those exposed to permanent hypothermic (32°C) ischemia to 56 ± 64 mm 3 ( n = 10) ( P < 0.05). In Expt. 2, normothermic ischemia and reperfusion resulted in an infarction of 211 ± 35 mm 3 ( n = 6). Intra-ischemic hypothermia (32°C) followed by 21 h of normothermic reperfusion resulted in 17 ± 12 mm 3 of infarction ( n = 9) ( P < 0.001). Hypothermia for either the first or second 1.5 h of the 3 h ischemic insult reduced the infarct volume to 116 ± 76 mm 3 ( n = 6) ( P < 0.05) or 108 ± 73 mm 3 ( n = 7) ( P < 0.01), respectively. Delaying the induction of hypothermia by 1.5 h and subsequently maintaining the temperature at 32°C during the first 1.5 h of reperfusion resulted in a reduction in infarct volume to 56 ± 66 mm 3 ( n = 7) ( P < 0.01). In Expt. 3, hypothermic ischemia followed by prolonged reperfusion (3 days) resulted in 31 ± 25 mm 3 ( n = 7) of infarction, versus 198 ± 28 mm 3 ( P < 0.001) in normothermic controls ( n = 7). In Expt. 4, normothermic ischemia and reperfusion resulted in a mean infarct volume of 166 ± 27 mm 3 ( n = 7). Delaying the onset of hypothermia until just prior to reperfusion resulted in a reduction in infarct volume to 65 ± 54 mm 3 ( n = 5) ( P < 0.05). Hyperthermic ischemia (40°C) increased injury, 245 ± 84 mm 3 ( n = 5) ( P < 0.05). These results demonstrate that mild intra-ischemic temperature reductions can attenuate cortical infarction with both permanent and transient focal ischemia. Furthermore, following transient focal ischemia, delayed hypothermia can still result in amelioration of injury.