Acute myocardial beta-adrenergic receptor dysfunction after cardiopulmonary bypass in patients with cardiac valve disease. Duke Heart Center Perioperative Desensitization Group.
BACKGROUND: Patients with cardiac valve disease (CVD) frequently have congestive heart failure (CHF) and chronic myocardial beta-adrenergic receptor (beta AR) desensitization. Cardiac surgery requiring cardiopulmonary bypass (CPB) is associated with increased plasma catecholamine concentrations, which might worsen myocardial beta AR function. We therefore tested the hypothesis that acute beta AR 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 beta AR density and adenylyl cyclase (AC) activity. Plasma catecholamine concentrations increased 3-fold during CPB (P < 0.01). Although beta AR density remained constant, isoproterenol-stimulated AC activity decreased significantly (approximately 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 beta AR dysfunction during CPB. CONCLUSIONS: Acute myocardial beta AR 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 beta AR signal transduction pathway at the level of the AC moiety. This information should facilitate development of agents designed to prevent acute myocardial beta AR dysfunction during CPB, potentially leading to improved outcome in this high-risk population.
Gerhardt, MA; Booth, JV; Chesnut, LC; Funk, BL; el-Moalem, HE; Kwatra, MM; Schwinn, DA
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