Enhanced in vivo and in vitro contractile responses to beta(2)-adrenergic receptor stimulation in dogs susceptible to lethal arrhythmias

The response to beta -adrenergic receptor (beta -AR) stimulation was evalua ted in both isolated cardiomyocytes (video edge detection) and the intact a nimal (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 i soproterenol provoked similar contractile and heart rate responses in each group of dogs. Either beta (1)-AR (bisoprolol) or beta (2)-AR (ICI-118551) antagonists reduced the isoproterenol response, with a larger reduction not ed after the beta (1)-AR blockade. In contrast, after infarction, isoproter enol induced a significantly larger Vcf and heart rate response in the susc eptible animals that was eliminated by beta (2)-AR blockade. The single-cel l isotonic shortening response to isoproterenol (100 nM) was also larger in cells obtained from susceptible compared with resistant dogs and was reduc ed to a greater extent by beta (2)-AR blockade in the susceptible dog myocy tes (S, - 48%, n = 6; R, - 15%, n = 9). When considered together, these dat a suggest that myocardial infarction provoked an enhanced beta (2)-AR respo nse in susceptible, but not resistant, animals.