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
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.