Biochemical effects of ischemia on isolated, perfused rat heart tissues

Abstract

Isolated working rat hearts perfused with Krebs-Hensleit buffer were arrested and made ischemic. After 22 min, the hearts were reperfused with buffer, yielding restoration of function. Nucleotide levels rose and fell in the cardiac tissue as ischemia was imposed; the changes were consistent with the energy needs of the tissue. ATP concentrations in the tissues fell by 75% during ischemia, AMP levels were low initially and subsequently rose 5-fold, and ADP levels were essentially unchanged. Upon reperfusion ATP levels rebounded, although not to initial values, and AMP returned to initial values. During ischemia, there was a 10-fold or greater rise in inosine, hypoxanthine, and xanthine levels which fell to normally low levels upon reperfusion. Lactate dehydrogenase (LDH) activity rose during ischemia and returned to baseline upon reperfusion. Changes in LDH isozyme distribution suggest that, during ischemia, there is an increased proportion of liver-associated forms which returns to normally low levels upon reperfusion. Glutamate oxalacetate transaminase activity rose slightly at 5 min of ischemia, but, by 22 min of ischemia, it had fallen to 60% of initial values. Upon reperfusion, activity rose and, by 15 min, had reached 127% of initial values. On the other hand, there is no significant change in levels of extractable creatine kinase or isocitrate dehydrogenase activities as a result of the various conditions imposed on the hearts. As an index of protein oxidation, carbonyl levels in extractable protein rose during ischemia and were over four times the initial values at 5 min of reperfusion but, with continued reperfusion, declined to approximately 150% of initial values at 15 min.