Nucleotide metabolism and cellular damage in myocardial ischemia.

Adenine nucleotide metabolism is greatly altered by myocardial anoxia or ischemia, both of which induce depletion of ATP and of the total adenine nucleotide pool. The depletion occurs at variable rates depending upon the nature of the model and the severity and conditions of the injury. In ischemia, the decrease in both ATP and the adenine nucleotide pool is due to an inadequate rate of production of high-energy phosphate relative to the demand of the heart for energy. In the process of capturing the high-energy phosphate of ADP, AMP is produced via myokinase and is degraded to nucleosides and ultimately to bases. In the early phase of ischemia, ADO and INO are the chief metabolites produced. A small quantity of XAN and large quantities of HX accumulate with time until eventually HX replaces INO as the principal metabolite of the pool. The biology of myocardial ischemic cell damage in the dog heart is summarized with respect to the depletion of ATP and total adenine nucleotide pool. Myocytes can survive with about 25% of the ATP of control tissue but exhibit a variety of defects that persist for minutes to days. At the onset of irreversibility, the dead tissue invariably exhibits virtually no ATP and a 65% or greater depletion in the total adenine nucleotide pool. It is not known whether these changes in ATP and the pool are directly or indirectly related to the development of irreversibility. In any event, the transition to cell death appears to be gradual.