Beta-adrenergic function in a congestive cardiomyopathy model

Abstract

We investigated the cardiac beta-adrenergic-adenylate cyclase (AC) system in turkeys inbred for congestive cardiomyopathy (CCM) and the relation of this system to echocardiographically determined left ventricular shortening fraction (LVSF) in individual 56-day-old birds. The isoproterenol (Iso)-stimulated, NaF-stimulated, and basal AC activities in CCM birds were decreased to 69, 72, and 86%, respectively, of control values, P less than 0.05. By linear regression analysis there was significant direct correlation of initial LVSF in CCM birds with each of the following: change in heart rate (HR) after Iso function; Iso-stimulated, NaF-stimulated, and basal AC activities, and density of beta-adrenergic receptors. In addition, we investigated the effect of Iso infusion (0.4 microgram X kg-1 X min-1) on systemic hemodynamics. In CCM birds the initial LVSF was 72% of the control value, P less than 0.01; the initial HR was 112% of the control value, P less than 0.01. During Iso infusion both the LVSF and HR in control birds were increased, whereas in CCM turkeys with marked cardiac dilatation neither of these parameters changed. In 10-day-old CCM turkeys, which show no cardiac dilatation, NaF-stimulated AC activity was reduced to 70% of the control values, whereas basal and Iso-stimulated AC activities were unchanged. Thus an abnormality in the beta-adrenergic-adenylate cyclase system is present in CCM birds before development of cardiac dilatation; when cardiac dilatation is severe, a global defect in this system can be directly related to depressed inotropic and chronotropic responsiveness to Iso infusion in individual turkeys.