Acute myocardial β-adrenergic receptor dysfunction after cardiopulmonary bypass in patients with cardiac valve disease

Background - Patients with cardiac valve disease (CVD) frequently have congestive heart failure (CHF) and chronic myocardial β-adrenergic receptor (βAR) desensitization. Cardiac surgery requiring cardiopulmonary bypass (CPB) is associated with increased plasma catecholamine concentrations, which might worsen myocardial βAR function. We therefore tested the hypothesis that acute βAR dysfunction occurs during CPB in patients with CVD. Methods and Results - After informed consent, 50 patients were enrolled. Right atrial biopsy samples were obtained at initiation and conclusion of CPB to assess βAR density and adenylyl cyclase (AC) activity. Plasma catecholamine concentrations increased 3-fold during CPB (P<0.01). Although βAR density remained constant, isoproterenol-stimulated AC activity decreased significantly (≃30%; P<0.005). AC activity decreased 22% and 24% with direct G protein (NaF) or AC (manganese) activation, respectively. Patients with or without preoperative CHF exhibited similar degrees of acute myocardial βAR dysfunction during CPB. Conclusions - Acute myocardial βAR dysfunction occurs during CPB in patients with severe CVD requiring surgical correction, with or without preexisting CHF. The primary underlying mechanism involves functional uncoupling of the βAR signal transduction pathway at the level of the AC moiety. This information should facilitate development of agents designed to prevent acute myocardial βAR dysfunction during CPB, potentially leading to improved outcome in this high-risk population.