© 1993 by European Society of Cardiology
Copyright © 1993, European Society of Cardiology
β Adrenoceptor recovery after heart failure in the dog
Department of Medicine, Division of Cardiology, St Michael's Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada: G Larosa, P W Armstrong, C Forster; Department of Pharmacology, University of Toronto, Ontario, Canada: P Seeman.
Correspondence to Giulia Larosa.
Objective: The role of myocardial β receptors in pacing induced congestive heart failure is uncertain. The aims of the study were therefore (1) to examine total β adrenoceptor density in canine left ventricle during pacing induced heart failure; and (2) to evaluate whether there is a relationship between β adrenoceptor numbers and circulating noradrenaline during progression of heart failure. Methods: Heart failure was examined at different stages: early (after 1 week of pacing at 250 beats·min–1); peak (after 4 weeks of pacing); and after recovery (4 weeks after pacing was discontinued). Myocardial β adrenoceptor density was assessed by radioligand binding with iodocyanopindolol. Plasma noradrenaline was determined by high performance liquid chromatography with electrochemical detection. Results: Compared to control, left ventricular β adrenoceptor density was: (1) not significantly different in early heart failure, at 2540(SEM 460) v 3160(260) fmol·g–1 wet weight in control; (2) decreased 63% at peak heart failure [1180(100) fmol·g–1, p<0.01]; and (3) restored to control density after recovery from heart failure [3430(540) fmol·g–1]. The β adrenoceptor dissociation constant was unaltered throughout. There was an inverse correlation between myocardial β adrenoceptor density and plasma noradrenaline (r = –0.785, p<0.01). Conclusions: The progressive decline in β adrenoceptor density as heart failure develops and the capacity of β adrenoceptors to return to control levels after recovery from the experimental heart failure state suggests that there is a reversible abnormality in β adrenoceptors during heart failure.
Cardiovascular Research 1993;27:489-493
KEYWORDS β adrenoceptors; congestive heart failure; recovery; rapid ventricular pacing; myocardium; iodocyanopindolol; plasma noradrenaline
We are grateful to Etienne Grima, Andrea Konig-Diraddo, George Naik, and Carla Ulpian for their excellent technical assistance. We would also like to thank Medtronics Canada for their generous supply of pacemakers. This work was supported by the Heart and Stroke Foundation of Ontario and the Pettit Fund (University of Toronto, Division of Cardiology).
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