Enhanced in vivo and in vitro contractile responses to beta2-adrenergic receptor
stimulation in dogs susceptible to lethal arrhythmias.
Houle, Melanie S., Ruth A. Altschuld, and George E. Billman.
Departments of 1Physiology and Cell Biology and 2Molecular and Cellular
Biochemistry, The Ohio State University, Columbus, Ohio 43210
APStracts 8:0335A, 2001.
The response to beta-adrenergic receptor (beta-AR) stimulation was evaluated in both
isolated cardiomyocytes (video edge detection) and the intact animal (echocardiography)
in dogs either susceptible (S) or resistant (R) to ventricular fibrillation induced by a 2-min
coronary occlusion during the last minute of exercise. In the intact animal, velocity of
circumferential fiber shortening (Vcf) was evaluated both before (n = 27, S = 12 and R =
15) and after myocardial infarction. Before infarction, increasing doses of isoproterenol
provoked similar contractile and heart rate responses in each group of dogs. Either beta1-
AR (bisoprolol) or beta2-AR (ICI 118,551) antagonists reduced the isoproterenol
response, with a larger reduction noted after the beta1-AR blockade. In contrast, after
infarction, isoproterenol induced a significantly larger Vcf and heart rate response in the
susceptible animals that was eliminated by beta2-AR blockade. The single-cell isotonic
shortening response to isoproterenol (100 nM) was also larger in cells obtained from
susceptible compared with resistant dogs and was reduced to a greater extent by beta2-
AR blockade in the susceptible dog myocytes (S, «minus»48%, n = 6; R, «minus»15%, n
= 9). When considered together, these data suggest that myocardial infarction provoked
an enhanced beta2-AR response in susceptible, but not resistant, animals.
Received 20 March 2001; accepted in final form 24 May 2001
APS Manuscript Number A0264-1.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 29 June 2001