Enhanced in vivo and in vitro contractile responses to β₂-adrenergic receptor stimulation in dogs susceptible to lethal arrhythmias

Abstract

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 beta(1)-AR (bisoprolol) or beta(2)-AR (ICI-118551) antagonists reduced the isoproterenol response, with a larger reduction noted after the beta(1)-AR blockade. In contrast, after infarction, isoproterenol induced a significantly larger Vcf and heart rate response in the susceptible animals that was eliminated by beta(2)-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 beta(2)-AR blockade in the susceptible dog myocytes (S, -48%, n = 6; R, -15%, n = 9). When considered together, these data suggest that myocardial infarction provoked an enhanced beta(2)-AR response in susceptible, but not resistant, animals.

Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death

“…There was no evidence of impaired global left ventricular structure or function after infarction, as has been previously reported in this model (6,7,22). Left ventricular fractional shortening was unchanged after MI (41 Ϯ 1.6 vs. 40.6 Ϯ 0.9%, baseline and 8 wk post-MI, respectively; P ϭ NS).…”

Cardiac β-adrenergic responsiveness with exercise

“…Work from the Billman laboratory have also demonstrated that exercise training signiWcantly reduced both the in vivo and the in vitro contractile response to 2-adrenergic receptor stimulation in dogs susceptible to ventricular Wbrillation (VT). These studies also showed that 10 weeks of endurance exercise training restored 1-adrenergic receptor expression and protein content in VT susceptible dogs (Billman et al 2006;Holycross et al 2007;Houle et al 2001). Thus, the idea that training mediates its eVects on down regulating 2-adrenergic receptors is an interesting hypothesis that requires further testing.…”

Cardiac Effects of Exercise Training in Hypertension

“…However, AR2 speci�c adrenergic inotropic responses were attenuated in trained animals [92]. Exercise training has also been reported to attenuate the contractile responses to AR2 stimulation in dogs while restoring AR1 adrenergic receptor protein content [99][100][101]. Whether training exerts its effects on downregulating AR2s is an interesting idea that requires further testing.…”