INTERACTIONS BETWEEN HYPOTHERMIA AND THE LATENCY TO ISCHEMIC DEPOLARIZATION - IMPLICATIONS FOR NEUROPROTECTION

Background: The authors postulated that hypothermic neuroprotection ca n be attributed to a delayed onset of ischemic depolarization. Methods : Halothane-anesthetized rats were prepared for near-complete forebrai n ischemia. Direct current (DC) potential microelectrodes were placed in hippocampal CA1. The pericranial temperature was maintained at 31 d egrees C, 33 degrees C, 35 degrees C, or 37 degrees C (n = 6 per group ). Bilateral carotid occlusion with systemic hypotension was initiated for 10 min. The time to onset of the DC shift was recorded. In a seco nd experiment, rats were assigned to 37 degrees C or 31 degrees C for 10 min of ischemia, or to 31 degrees C for 14 min of ischemia (n = 8 p er group). These durations of ischemia were defined to allow 9 min of ischemic depolarization in the 37 degrees-10 min and 31 degrees C-14 m in groups. Neurologic and histologic outcomes were examined 7 days lat er.Results: Hippocampal CA1 time to depolarization increased with decr easing temperature (P < 0.0001). Time to depolarization was increased by approximately 4 min in the rats maintained at 31 degrees C compared with those at 37 degrees C. Time to repolarization during reperfusion was not affected by temperature. Increasing the duration of ischemia from 10 min to 14 min with the pericranial temperature maintained at 3 1 degrees C resulted in a duration of depolarization that was equivale nt in the 37 degrees C-10 min and 31 degrees C-14 min groups. However, hippocampal CA1 damage was not increased (31 degrees C-10 min = 4 +/- 1% dead neurons; 31 degrees C-14 min = 6 +/- 1% dead neurons, 95% CI, -1% to 3%; 37 degrees C-10 min = 90 +/- 17% dead neurons). Conclusion s: Despite similar durations of DC depolarization, outcome in hypother mic rats was markedly improved compared with normothermic rats. This i ndicates that hypothermic neuroprotection can be attributed to mechani sms other than the delay in time to onset of ischenlic depolarization.