Effects of Chronic Heart Failure on the Capacity of Glucagon to Enhance Contractility and Adenyl Cyclase Activity of Human Papillary Muscles

Glucagon has a positive inotropic effect in normal hearts but is ineffective in animals with chronic cardiac failure. To assess directly the influence of glucagon on the human myocardium, we measured contractility and activation of adenyl cyclase, the enzyme thought to mediate the inotropic action of glucagon, in left ventricular papillary muscles obtained from 12 patients at mitral valve replacement. On the basis of preoperative ventricular end-diastolic pressures and cardiac output (independent of papillary muscle data) patients were classified in three groups: normal, cardiac failure, and condition indeterminate. Concentration-response curves showed that glucagon caused a mean rise of 11% in peak papillary muscle tension and a rise of 12% in peak rate of tension development in the normal patients; myocardial adenyl cyclase activity from each normal patient rose after glucagon (average, 84%). In the papillary muscles of the patients with cardiac failure, glucagon did not augment either tension or adenyl cyclase activity. In contrast, contractility and adenyl cyclase activity increased after norepinephrine in both normal patients and those with cardiac failure. The indeterminate group had two patients whose papillary muscles responded to glucagon and two whose papillary muscles did not respond. Thus, direct study of human papillary muscles shows that chronic cardiac failure is uniformly associated with complete loss of the normal enhancement of contractility and associated activation of adenyl cyclase after glucagon. This perhaps explains the inefficacy of this drug in treating patients with chronic cardiac failure.