Yoshimasa Oyama, Justin Blaskowsky and Tobias Eckle* Pages 2199 - 2206 ( 8 )
Background: 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.
Methods: 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.
Results: 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).
Conclusion: 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.
Epinephrine, esmolol, myocardial ischemia and reperfusion injury, troponin, TTC, blood pressure, heart rate.
Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045, Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045, Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045