ACTIVATION AND INHIBITION OF THE ENDOGENOUS OPIOID SYSTEM IN HUMAN HEART-FAILURE

Background-In a canine model of congestive heart failure beta endorphi n concentrations were high and opioid receptor antagonists exerted ben eficial haemodynamic effects. In humans previous studies have suggeste d that opioid peptides may modify the perception of breathlessness and fatigue in heart failure. Methods-Plasma concentrations of beta endor phin were measured in patients with acute and chronic heart failure an d cardiogenic shock. A subgroup of eight patients with New York Heart Association (NYHA) class III-IV heart failure was assessed for acute h aemodynamic effects of naloxone, an opioid receptor antagonist. A sepa rate group of 10 patients with class II-III heart failure, was randomi sed to a double blind placebo controlled study of the effects of intra venous naloxone on cardiopulmonary exercise performance. Results-Plasm a concentrations of beta endorphin were usually normal in patients wit h chronic heart failure and did not correlate with severity as assesse d by NYHA class. In 29% of patients with acute heart failure and 71% o f those with cardiogenic shock beta endorphin concentrations were high . The median concentration in the cardiogenic shock group was signific antly higher than in either of the two heart failure groups and there was some evidence of a relation between beta endorphin concentrations and survival. At the doses tested, naloxone was unable to modify syste mic haemodynamics, exercise performance, or symptoms in patients with chronic congestive heart failure. Conclusions-Circulating concentratio ns of beta endorphin are usually normal in patients with chronic conge stive heart failure. Inhibition of the endogenous opioid system is unl ikely to have therapeutic potential in heart failure.