Esmolol improves left ventricular function via enhanced β-adrenergic receptor signaling in a canine model of coronary revascularization

Abstract

Background: Recent American Heart Association guidelines highlight the paucity of data on effectiveness and/or mechanisms underlying use of β-adrenergic receptor (βAR) antagonists after acute coronary syndromes in patients subsequently undergoing revascularization. It is important to assess whether βAR antagonists might protect the heart and improve ventricular function in this scenario. The authors therefore used esmolol (an ultra-short-acting βAR antagonist) to determine whether βAR antagonist treatment improves left ventricular function in a canine model of acute reversible coronary ischemia followed by coronary reperfusion during cardiopulmonary bypass (CPB). The authors also tested whether the mechanism includes preserved βAR signaling. Methods: Dogs were randomized to either esmolol or saline infusions administered during CPB (n = 29). Pre-CPB and end-CPB transmyocardial left ventricular biopsies were obtained; plasma catecholamine concentrations, myocardial βAR density, and adenylyl cyclase activity were measured. In addition, left ventricular systolic shortening and postsystolic shortening were determined immediately prior to each biopsy. Results: While βAR density remained unchanged in each group, isoproterenol-stimulated adenylyl cyclase activity decreased 26 ± 6% in the control group but increased 38 ± 10% in the esmolol group (pre-CPB to end-CPB, mean ± SD, P = 0.0001). Left ventricular systolic shortening improved in both groups after release of coronary (LAD) ligature; however, the esmolol group increased to 72 ± 23% of pre-CPB values compared to 48 ± 12% for the control group (P = 0.0008). Conclusions: These data provide prospective evidence that esmolol administration results in improved myocardial function. Furthermore, the mechanism appears to involve enhanced myocardial βAR signaling.