Endurance exercise training attenuates cardiac β2-adrenoceptor responsiveness and prevents ventricular fibrillation in animals susceptible to sudden death

Enhanced cardiac beta(2)-adrenoceptor (beta(2)-AR) responsiveness can increase susceptibility to ventricular fibrillation (VF). Exercise training can decrease cardiac sympathetic activity and could, thereby, reduce beta(2)-AR responsiveness and decrease the risk for VF. Therefore, dogs with healed myocardial infarctions were subjected to 2 min of coronary occlusion during the last minute of a submaximal exercise test; VF was observed in 20 susceptible, but not in 13 resistant, dogs. The dogs were then subjected to a 10-wk exercise-training program (n = 9 susceptible and 8 resistant) or an equivalent sedentary period (n = 11 susceptible and 5 resistant). Before training, the beta(2)-AR antagonist ICI-118551 (0.2 mg/kg) significantly reduced the peak contractile (by echocardiography) response to isoproterenol more in the susceptible than in the resistant dogs: -45.5 +/- 6.5 vs. -19.2 +/- 6.3%. After training, the susceptible and resistant dogs exhibited similar responses to the beta(2)-AR antagonist: -12.1 +/- 5.7 and -16.2 +/- 6.4%, respectively. In contrast, ICI-118551 provoked even greater reductions in the isoproterenol response in the sedentary susceptible dogs: -62.3 +/- 4.6%. The beta(2)-AR agonist zinterol (1 mu M) elicited significantly smaller increases in isotonic shortening in ventricular myocytes from susceptible dogs after training (n = 8, +7.2 +/- 4.8%) than in those from sedentary dogs (n = 7, +42.8 +/- 5.8%), a response similar to that of the resistant dogs: +3.0 +/- 1.4% (n = 6) and +3.2 +/- 1.8% (n = 5) for trained and sedentary, respectively. After training, VF could no longer be induced in the susceptible dogs, whereas four sedentary susceptible dogs died during the 10-wk control period and VF could still be induced in the remaining seven animals. Thus exercise training can restore cardiac beta-AR balance (by reducing beta(2)-AR responsiveness) and could, thereby, prevent VF.