Chronic opiate receptor inhibition in experimental congestive heart failure in dogs. Yatani, Akito, Naoaki Imai, Yoshihiro Himura, Masakuni Suematsu, and Chang-Seng Liang. Cardiology Research Laboratories, Department of Medicine (Cardiology Unit), University of Rochester Medical Center, Rochester, New York 14642
APStracts 3:0312H, 1996.
We have previously shown that acute administration of opiate receptor antagonists improves cardiac output, aortic blood pressure, systolic ventricular performance and the baroreflex function in conscious dogs with right-sided congestive heart failure (RHF). However, whether similar changes occur after chronic opiate receptor inhibition in congestive heart failure is not known. To determine the chronic effects of opiate receptor antagonism on RHF, we administered naltrexone (200 mg/day), a long acting orally active opiate receptor blocking agent, to RHF and sham-operated animals for 6 weeks. Naltrexone treatment had no effects on resting heart rate, right atrial pressure, aortic pressure or cardiac output in RHF dogs, but increased right and left ventricular dP/dt at rest and improved the dP/dt responses to isoproterenol. The inotropic responses to isoproterenol and forskolin in isolated right ventricular trabeculate muscle also were improved by chronic naltrexone in RHF. Myocardial [beta]-receptor density was reduced in the failing right ventricle compared to the control (58+/-3 vs. 108+/-6 fmol/mg protein, P&LT0.01), but was unaffected by addition of naltrexone treatment. Finally, naltrexone treatment prevented the decline in baroreflex sensitivity that occurred in RHF (-0.2+/-0.5 vs. -6.0+/-0.5 msec/mmHg, P&LT0.01). These effects of naltrexone did not occur in the sham-operated animals. Chronic opiate receptor blockade with naltrexone attenuates the development of reduced adrenergic inotropic responsiveness and baroreflex subsensitivity that occur in RHF. Since there was a similar improvement in the forskolin response in the absence of significant alterations in myocardial [beta]-adrenoceptor density after naltrexone treatment, the improvement in adrenergically mediated inotropic effects probably is mediated via a post-receptor mechanism. 

Received 29 December 1995; accepted in final form 12 July 1996.
APS Manuscript Number H1214-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 August 1996