Effect of therapeutic hypothermia vs δ-opioid receptor agonist on post resuscitation myocardial function in a rat model of CPR

Abstract

AIM: This study is to compare the effect of the δ-opioid receptor agonist, D-Ala(2)-D-Leu(5) enkephalin (DADLE) with normothermic control and therapeutic hypothermia on post resuscitation myocardial function and 72-h survival in a rat model of cardiac arrest and resuscitation.

METHODS: Ventricular fibrillation (VF) was induced in 15 male Sprague-Dawley rats. After 8 min of untreated VF, cardiopulmonary resuscitation was performed for 8 min before defibrillation. Animals were randomized to three groups of five: (a) normothermia; (b) hypothermia (32 °C); and (c) normothermia with DADLE intravenous infusion (1 mg/kg h(-1)). Hypothermia and drug infusion were started after successful defibrillation. Myocardial functions, including cardiac output (CO), left ventricular ejection fraction (LVEF), and myocardial performance index (MPI) were measured echocardiographically together with duration of survival.

RESULTS: The 72-h survival was significantly greater in the hypothermic group than in both DADLE and normothermic group (p = 0.02). However, the survival time of the DADLE treated animals was significantly longer than that of the normothermia group (51.8 ± 18.9 vs 18.8 ± 10.1h, p < 0.01). DADLE group showed significantly better CO (PR 60 min, p = 0.049), better LVEF (PR 60 min, p = 0.044; PR 240 min, p < 0.001) and lower MPI (PR 60 min, p = 0.043; PR 240 min, p = 0.045) than normothermic group. Hypothermia group also showed significantly better CO (PR 60m in, p = 0.044; PR 240 min, p = 0.007), better LVEF (PR 60 min, p = 0.001; PR 240 min, p < 0.001) and lower MPI (PR 60 min, p = 0.003; PR 240 min, p = 0.012) than the normothermic group.

CONCLUSIONS: DADLE attenuated post resuscitation myocardial dysfunction and increased short term survival time. However, the 72-h survival in the DADLE group was less than that in the hypothermia group