Gerhardt M A, Booth J V, Chesnut L C, Funk B L, el-Moalem H E, Kwatra M M, Schwinn D A
Department of Anesthesiology, Duke Heart Center, Duke University Medical Center, Durham, NC 27710, USA.
Circulation. 1998 Nov 10;98(19 Suppl):II275-81.
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.
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.
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.
心脏瓣膜病（CVD）患者常伴有充血性心力衰竭（CHF）和慢性心肌β-肾上腺素能受体（βAR）脱敏。需要体外循环（CPB）的心脏手术与血浆儿茶酚胺浓度升高有关，这可能会使心肌βAR功能恶化。因此，我们检验了这样一个假设，即在患有CVD的患者进行CPB期间会发生急性βAR功能障碍。
在获得知情同意后，招募了50名患者。在CPB开始时和结束时获取右心房活检样本，以评估βAR密度和腺苷酸环化酶（AC）活性。CPB期间血浆儿茶酚胺浓度增加了3倍（P < 0.01）。尽管βAR密度保持不变，但异丙肾上腺素刺激的AC活性显著降低（约30%；P < 0.005）。直接用G蛋白（氟化钠）或AC（锰）激活时，AC活性分别降低了22%和24%。术前有或无CHF的患者在CPB期间表现出相似程度的急性心肌βAR功能障碍。
在需要手术矫正的重度CVD患者中，无论术前有无CHF，CPB期间都会发生急性心肌βAR功能障碍。主要的潜在机制涉及βAR信号转导通路在AC部分水平的功能解偶联。这些信息应有助于开发旨在预防CPB期间急性心肌βAR功能障碍的药物，可能会改善这一高危人群的预后。
