Combining Epinephrine and Esmolol Attenuates Excessive Autophagy and Mitophagy in Rat Cardiomyocytes After Cardiac Arrest.

BACKGROUND: Recent experimental and clinical studies have indicated that the β-adrenergic effect of epinephrine significantly increases the severity of postresuscitation myocardial dysfunction. The aim of this study was to investigate whether the short-acting β1-selective adrenergic blocking agent, esmolol, would impact postresuscitation autophagy and mitophagy in cardiomyocytes in a rat cardiac arrest (CA) model.

METHODS: CA was induced in Sprague Dawley rats by epicardial ventricular fibrillation for 5 minutes. After successful resuscitation, the surviving rats were randomly divided into 2 groups that received femoral venous injections of epinephrine combined with either esmolol (EE group) or epinephrine (E group). Arterial blood samples were obtained at times 0, 30, and 180 minutes after return of spontaneous circulation. Surviving rats were euthanatized at 12 or 24 hours after return of spontaneous circulation, and the hearts were removed for histochemical analysis, electron microscopy, Western blotting, and TUNEL experiment.

RESULTS: Relative to the E group, the EE group had reduced N-Methyl-D-Aspartate receptors expression and reduced arterial lactate levels (P < 0.05), suggesting that epinephrine/esmolol can attenuate postresuscitation antioxidation and apoptosis. This protective effect also correlated with a reduction of excessive autophagy and mitophagy in the cardiomyocytes, as evidenced by a reduction in Beclin-1 and Parkin expression (P < 0.05).

CONCLUSIONS: Esmolol significantly alleviates postresuscitational autophagy, including mitophagy, and cardiomyocyte apoptosis in a rat CA model.