Abstract 17382: Pharmacologically Induced Hypothermia With Cannabinoid Receptor Agonist Win55, 212-2 Improves Cardiac Function in a Rat Model of Cardiac Arrest

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Introduction: Cannabinoid receptors (CB) located in the preoptic anterior hypothalamus play a major role in thermoregulation. Our previous work demonstrates that the CB antagonist WIN55, 212-2 (WIN) can induce hypothermia in rats post ROSC. However the effects of pharmacologically induced hypothermia on myocardial function compared to traditional mechanical hypothermia (MH) are not known.

Hypothesis: Hypothermia produced by WIN results in better post-resuscitation myocardial function compared to MH.

Methods: Ventricular fibrillation (VF) was induced in 18 Sprague-Dawley rats weighing between 450 and 550g. VF was untreated for 6 min followed by 8 min of CPR. Resuscitation was then attempted with defibrillation. Animals were randomized into 3 groups five min after resuscitation: N, MH, WIN hypothermia (WH). N and hypothermia (H) were respectively defined as 37°C and 33°C. For the WH group, WIN was administered and for the MH and N groups a vehicle (2%Tween-80 in 0.9% NaCl solution) was administered, both at (1mg/kg/h) for two hours. H in the MH group was induced with ice packs. Ejection fraction (EF), cardiac output (CO) and myocardial performance index (MPI) were measured at baseline, 1, 2, 3 and 4 hours after ROSC with echocardiography.

Results: All animals showed impaired CO, EF, and MPI immediately after resuscitation compared to baseline values. Target core temperature (33°C) was constant in both groups. Beginning 1 hour after infusion, myocardial function was significantly improved in WIN versus MH treated animals (Fig 1).

Conclusion: Pharmacologic hypothermia induced by WIN improves cardiac function significantly after CPR when compared with MH. The underlying mechanism is unclear and should be a topic of future study. Figure 1. * p<0.05 vs normothermia; # p<0.05 vs WIN hypo

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