Assessment of hemodynamic function and tolerance to ischemia in the absence or presence of calcium antagonists in hearts of isoproterenol-treated, exercise-trained, and sedentary rats.

The effects of cardiac hypertrophy on the structure, function and tolerance to ischemia of rat hearts have been investigated. Multiple injections of low doses of isoproterenol (ISO) resulted in an increase of heart weight/body weight ratio by 60%, and a decrease of myocardial creatine kinase activ- ity by 25%, as compared to normal rats. Compared to age-matched control rats, rats submitted to a swimming program had a higher heart weight by 20%, but similar values of heart weight to body weight ratio. In isolated perfusion, the functional capacities of hearts from ISO-treated rats were severely depressed compared to normal rat hearts whereas exercise-trained rat hearts performed as well or even better than control hearts. The func- tional recovery of NO-treated hearts following cardioplegia-induced arrest for 20 min at 37 "C was significantly worse than the recovery of normal hearts, but hearts of exercise-trained rats showed a significantly better recovery than control hearts. Exercise training results in improvement of myo- cardial blood supply resulting in better preserva- tion of the heart during ischemia, compared to nor- mal hearts. Addition of a combination of verapa- mil and diltiazem to the cardioplegic solution fol- lowed by ischemic arrest for 20 min at 37 "C result- ed for ISO-treated rat hearts in an improved recov- ery of cardiac output (99'/) compared to cardio- plegia in the absence of these drugs (72%). In exercise-trained and control rat hearts, calcium an- tagonists improved the recovery from cardioplegic arrest of cardiac output from 90% to 92% and from 71% to 87%, respectively. Myocardium of ISO-treated rats showed foci of subendocardial in- farction and fibrosis, whereas the myocardium of physically stressed animals and of normal rats had no abnormalities. Considering the histological sim- ilarities between ISO-treated rat hearts and lesions observed in human hearts with coronary artery dis- ease and cardiac hypertrophy, the present study suggests that the presence of verapamil and diltia- zem during cardioplegic arrest favors the func- tional recovery from cardiac surgery. (Eur J Cardio-thorac Surg (1988) 2: 448-4521