Dose-dependent Effects of Esmolol-epinephrine Combination Therapy in Myocardial Ischemia and Reperfusion Injury.

Abstract

Animal studies on cardiac arrest found that a combination of epinephrine with esmolol attenuates post-resuscitation myocardial dysfunction. Based on these findings, we hypothesized that esmololepinephrine combination therapy would be superior to a reported cardioprotective esmolol therapy alone in a mouse model of myocardial ischemia and reperfusion (IR) injury. C57BL/6J mice were subjected to 60 min of myocardial ischemia and 120 min of reperfusion. Mice received either saline, esmolol (0.4 mg/kg/h), epinephrine (0.05 mg/kg/h), or esmolol combined with epinephrine (esmolol: 0.4 mg/kg/h or 0.8 mg/kg/h and epinephrine: 0.05 mg/kg/h) during reperfusion. After reperfusion, infarct sizes in the area-at-risk and serum cardiac troponin-I levels were determined. Hemodynamic effects of drugs infused were determined by measurements of heart rate (HR) and mean arterial blood pressure (MAP) via a carotid artery catheter. Esmolol during reperfusion resulted in robust cardioprotection (esmolol vs. saline: 24.3±8% vs. 40.6±3% infarct size), which was abolished by epinephrine co-administration (38.1±15% infarct size). Increasing the esmolol dose, however, was able to restore esmolol-cardioprotection in the epinephrine-esmolol (18.6±8% infarct size) co-treatment group with improved hemodynamics compared to the esmolol group (epinephrine-esmolol vs. esmolol: MAP 80 vs. 75 mmHg, HR 452 vs. 402 beats/min). These results confirm earlier studies on esmolol-cardioprotection from myocardial IR-injury and demonstrate that a dose optimized epinephrine-esmolol co-treatment maintains esmolol-cardioprotection with improved hemodynamics compared to esmolol treatment alone. These findings might have implications for current clinical practice in hemodynamically unstable patients suffering from myocardial ischemia.