Hypothermia attenuates postresuscitation myocardial dysfunction by inhibiting beta adrenergic signaling

Introduction: Therapeutic hypothermia reduce the severity of post-resuscitation myocardial dysfunction caused by epinephrine administered during cardiopulmonary resuscitation (CPR), and the mechanism remains unclear. Hypothesis: hypothermia may reduce the concentration of cyclic adenosine monophosphate (cAMP), a second messenger of beta-adrenergic receptor activity. Methods: Thirty two male Sprague-Dawley rats were randomized to four groups: 1) normothermic placebo control; 2) normothermic epinephrine; 3) hypothermic placebo control; and 4) hypothermic epinephrine. Ventricular fibrillation was induced electrically and untreated for 8 mins. Hypothermia was initiated coincident with the start of CPR and maintained at 33 ± 0.2°C for 4 hrs after resuscitation and animals were then euthanized. Either placebo or epinephrine was administered 5 mins after the start of CPR and 3 mins before defibrillation. Post-resuscitation ejection fraction was measured hourly for 4 hrs. The hearts were then harvested for cAMP and Inositol 1,4,5-trisphosphate (IP3) assay analysis. Results: All animals were successfully resuscitated except one in normothermic placebo group. Epinephrine significantly increased coronary perfusion pressure during CPR (26.5±6.23mmHg vs 21.14±1.95 mmHg P<0.05). Post-resuscitation myocardial function was significantly impaired in normothermic epinephrine group compared with other three groups (figure 1). The concentration of myocardial cAMP was double in normothermic epinephrine group (655.06±447.63 umol/L) when compared to that in hypothermic epinephrine group (302.51±97.98 umol/L P<0.05). However, there was no difference in the concentration of IP3 in all four groups. Conclusions: The potential mechanism of myocardial protective effect of hypothermia may involve the reduced activities of β-receptors.