DECREASE IN ISCHEMIC TOLERANCE WITH AGING IN ISOLATED-PERFUSED FISCHER-344 RAT HEARTS - RELATION TO INCREASES IN INTRACELLULAR NA+ AFTER ISCHEMIA

M. TANI, Y. SUGANUMA, H. HASEGAWA, K. SHINMURA, Y. EBIHARA, Y. HAYASHI , X.-D. GUO AND M. TAKAYAMA. Decrease in Ischemic Tolerance with Aging in Isolated Perfused Fischer 344 Rat Hearts: Relation to Increases in Intracellular Na+ After Ischemia. Journal of Molecular and Cellular C ardiology (1997) 29, 3081-3089. While the ischemic tolerance of the my ocardium has been reported to decrease with senescence, it is not know n when and how this occurs. Our objectives were to determine whether t he tolerance to myocardial ischemia in rats decreased before the onset of senescence and whether an increase in myocardial ionic imbalance w as associated with an enhanced myocardial injury with aging. Hearts we re isolated from Fischer 344 rats categorized as young (12 weeks old), mature adult (24 weeks), middle-aged (50 weeks) or senescent (100 wee ks). Hearts were perfused isovolumically by the Langendorff procedure and subjected to 25 min of global ischemia followed by 30 min of reper fusion. In the 50- and 100-week-old rats, the recovery of ventricular function and high-energy phosphate levels was lower and there was incr eased incidence of ventricular fibrillation after 25 min of global isc hemia followed by reperfusion, The release of creatine kinase and lact ate dehydrogenase during reperfusion was greater in the 50- and 100-we ek-old rats than in the 12- and 24-week-old rats, indicating the irrev ersible myocardial damage due to ischemia-reperfusion increased by mid dle-age. Intracellular levels of Na+ and K+ before ischemia were highe r in the 50- or 100-week-old rats than in the 12-week-old rats, The in crease in intracellular Na+ at end of ischemia was greater in the olde r (50-week-old, 215% of the pre-ischemic value; 100-week-old, 232% of the pre-ischemic value) than in the younger rats (12-week-old, 158% of the pre-ischemic value). Results indicated that the rat heart becomes more vulnerable to ischemia in middle-age. This decrease in ischemic tolerance may be caused by an acceleration of myocardial ionic imbalan ce with aging. (C) 1997 Academic Press Limited.