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2-adrenoceptor Responsiveness and Prevents Ventricular Fibrillation in Animals Susceptible to Sudden Death
1 Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA; Davis Heart and Lung Research Institute, Columbus, OH, USA
2 Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA
3 Davis Heart and Lung Research Institute, Columbus, OH, USA
* To whom correspondence should be addressed. E-mail: billman.1{at}osu.edu.
Enhanced cardiac 
2-adrenoceptor (2-AR) responsiveness can increase the susceptibility to ventricular fibrillation (VF). Exercise training can decrease cardiac sympathetic activity and could, thereby, reduce 2-AR responsiveness and decrease the risk for VF. Therefore, a 2-minute coronary occlusion was made during the last minute of a submaximal exercise test in dogs with healed myocardial infarctions; 20 had VF (S, susceptible) 13 did not (R, resistant). The dogs then received either a 10-week exercise training program (S n=9, R n=8) or an equivalent sedentary period (S n=11, R n=5). Before training, the 2-AR antagonist ICI 118,551 (0.2 mg/kg) significantly reduced the peak contractile (by echocardiography) response to isoproterenol (ISO) more in the susceptible animals (S -45.5±6.5% vs. R -19.2±6.3%)compared to resistant dogs. After training, the resistant and the susceptible dogs exhibited similar responses to the 2-AR antagonist (S -12.1±5.7% vs. R -16.2±6.4%). In contrast, ICI 118,551 provoked even greater reductions in the ISO response in the sedentary susceptible dogs (-62.3±4.6%). The 2-AR agonist zinterol (1µM) 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 the resistant dogs (trained, n=6, +3.0±1.4%; sedentary, n=5, +3.2±1.8%). After training, VF could no longer be induced in the susceptible dogs, while four sedentary susceptible dogs died during the 10-week control period and the remaining 7 animals still had VF when tested. Thus, exercise training can restore cardiac -adrenoceptor balance (by reducing 2-AR responsiveness) and could, thereby, prevent VF.
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