Metoprolol Prevents Cardiac Oxidative Stress Associated with Myocardial Ischemia/Reperfusion Injury

Abstract

Metoprolol, a selective β1 adrenergic receptor blocker is cardioprotective in a setting of ischemia /reperfusion injury. However, it remains controversial whether the cardioprotection is mediated by reducing oxidative stress. We tested the hypothesis that metoprolol prevents early cardiac oxidative stress during myocardial ischemia/reperfusion injury. Male Sprague‐Dawley rats were pretreated with metoprolol (1 mg/kg, i.v.) 10 min prior to a 30 min myocardial ischemia followed by 24 h reperfusion. Cardiac troponin I and T, and fatty acid binding protein 3 were measured at baseline (pre‐ischemia), 1, 2, 4, and 24 h after reperfusion using an MSD assay kit. To determine whether oxidative stress is involved in early myocardial ischemia/reperfusion injury, cardiac myosin binding protein C (MyBPC) carbonylation was determined by western blotting at 1 h after reperfusion. Infarct size was determined by TTC and Evans blue staining at 24 h after reperfusion. Ischemia/reperfusion injury significantly elevated plasma levels of cardiac injury markers for up to 24 h, reaching the peak at 1 h after reperfusion, increased MyBPC carbonylation 3.9‐fold, and caused a 56±6.2% infarct of the area at risk (n=6). Metoprolol attenuated peak and temporal plasma levels of cardiac injury markers, reduced MyBPC carbonylation by 52% (p<0.01), and reduced infarct size to 33±6.9% of the area at risk (n=6, P<0.01). Cardiac injury markers were positively correlated with infarct size, suggesting that metoprolol prevents cardiac oxidative stress associated with myocardial ischemia/reperfusion injury.