CHANGES IN ISCHEMIC TOLERANCE AND EFFECTS OF ISCHEMIC PRECONDITIONINGIN MIDDLE-AGED RAT HEARTS

Background Although both clinical and animal studies have shown that i schemic tolerance is reduced in the senescent myocardium, it has not b een clarified when myocardium becomes more vulnerable to ischemia. Pre conditioning protects the hearts of young adult animals of various spe cies, but its effects are not identical in human studies. We investiga ted whether ischemic tolerance and the effect of preconditioning decre ased in isolated hearts of middle-aged rats. Methods and Results The h earts of young adult rats (12 weeks old: group Y, n=44) and middle-age d rats (50 weeks old: group M, n=44) were subjected to global ischemia for 15, 20, or 25 minutes followed by reperfusion. Hearts were also s ubjected to preconditioning and then to 20 (group Y, n=22) or 15 (grou p M, n=22) minutes of ischemia followed by reperfusion. Left ventricul ar developed pressure (LVDP) was decreased by 40% to 60%, and the leve l of ATP was decreased by 60% to 70% in group M compared with group Y. Preconditioning increased LVDP (% LVDP, 40.5% to 72.4%) and levels of high-energy phosphates (ATP, 11.8 to 14.1; creatine phosphate, 17.0 t o 23.1 mu mol/g dry wt) and reduced left ventricular end-diastolic pre ssure (LVEDP, 32.8 to 10.3 mm Hg), creatine kinase release (257 to 132 U/g dry wt), and ryanodine-sensitive sarcoplasmic reticulum Ca2+ rele ase after ischemia in group Y. Preconditioning exerted opposite effect s in group M (% LVDP, 45.9% to 15.8%; LVEDP, 21.0 to 28.5 mm Hg; ATP, 14.1 to 8.5 mu mol/g dry wt; and CK release, 176 to 332 U/g dry wt). P reconditioning was associated with increases in the incidence of reper fusion-induced Ventricular fibrillation (0% to 62.5%) and the rate of sarcoplasmic reticulum Ca2+ release in group M. Conclusions These resu lts indicate that hearts became more vulnerable to ischemia with age a nd that the beneficial effects of preconditioning were reversed in mid dle-aged rat hearts.