Abstract

Background: We investigated the effects of hypothermia treatment alone and in combination with experimental bilateral lower limb remote ischemic preconditioning (RIPC) in rats undergoing experimental hemorrhagic shock. Previously we showed that RIPC alone improved survival. Methods: In the hypothermia alone study, adult Sprague Dawley rats (both genders) were randomized to hypothermia (n=16) or control group (n=15); in a combination study, rats were randomized to hypothermia plus RIPC (n=11) or control group (n=10). Rats were anesthetized with intraperitoneal ketamine/xylazine. Therapeutic hypothermia (Thermosuit) was started at 5 minutes after mean blood pressure (MBP) reached 30 mmHg. Core temperature was maintained at ~ 32 °C until blood volume was fully restored. RIPC was induced by 4 cycles of inflating small bilateral pressure cuffs to 200 mmHg around the femoral arteries for 5 minutes, followed by 5 minute deflation of the cuffs prior to hemorrhagic shock. In the control group, body temperature was maintained at 37 °C during the procedure. Hemorrhagic shock was induced by withdrawing blood from the carotid artery. Target mean blood pressure of 30 mmHg was maintained for 30 minutes followed by reinfusion of shed blood within the next 30 min. Rats were allowed recovery and the primary endpoint was survival rate at 6 weeks. Results: In the setting of hypothermia alone, 4 of 15 (26.7 %) rats in the control group and 11 of 16 (68.8 %; p = 0.032) rats in the hypothermia group survived at 6 weeks. In the combination study, 1 of 10 (10 %) rats in the control group and 7 of 11 (63.6 %; p = 0.024) rats in the hypothermia plus RIPC group survived at 6 weeks. Kaplan Meier Survival Curves are shown in Fig1. Conclusions: Hypothermia alone and combination with RIPC significantly improved long term survival in rats subjected to hemorrhagic shock. Hypothermia and RIPC did not show survival rates greater than hypothermia alone.

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