Local mild hypothermia induced by intra-arterial cold saline infusion prolongs the time window of onset of reperfusion injury after transient focal ischemia in rats

Abstract

Objectives: The aims of this study were to determine the effects of intra-arterial local hypothermia on infarct volume in rats with different durations of ischemia and to determine whether hypothermia can prolong the therapeutic time window compared with reperfusion without hypothermia.Methods: Adult male Sprague-Dawley rats weighing 260–300 g were divided into control group (permanent MCA occlusion), normothermia groups (NT groups) and hypothermia groups (HT groups). NT groups included rats induced with blood reperfusion for 1.5, 2, 2.5 or 3 hour ischemia. In the HT groups with ischemia of 1.5, 2, 2.5 or 3 hours, 6 ml 20°C normal saline solution was flushed at a speed of 0.6 ml/min, beginning 10 minutes before blood reperfusion. The infarct volumes of brains stained by TTC were observed 48 hours later. Brain temperature, blood flow and neurological scores were also recorded during this procedure.Results: In the 1.5, 2, 2.5 and 3 hour ischemic groups, cold saline (20°C infusion via the MCA) rapidly reduced the temperature of the MCA-supplied ischemic territory in the cortex from 37.0–37.1 to 32.8–33.2°C and in the striatum from 37.3–37.5 to 33.2–33.3°C. In NT groups, the average total infarct volumes of 1.5 and 2 hour ischemia (29.80 ± 2.20 and 34.29 ± 2.14%, respectively) were significantly less than that of the control group (48.41 ± 5.82%), but the average total infarct volumes of the 2.5 and 3 hour ischemia groups (47.31 ± 4.72 and 50.17 ± 8.08%, respectively) did not change. Compared with the ischemia groups without local saline infusion, the average total infarct volumes of 1.5, 2 and 2.5 hours with local saline infusion to the ischemic territory (16.79 ± 2.51, 23.09 ± 4.63% and 25.19 ± 7.82%, respectively) decreased significantly, but the average total infarct volume of 3 hour ischemia with local saline infusion (43.30 ± 2.62%) was not different.Conclusion: Local cold saline infusion to the ischemic territory before reperfusion can lead to mild hypothermia of the ischemic territory and can prolong the therapeutic time window of reperfusion from 2 to 2.5 hours. Refinements of the cooling process, optimal target temperature, duration of the therapy and most importantly, clinical efficacy, require further study.