Total ischemia in dog hearts, in vitro. 1. Comparison of high energy phosphate production, utilization, and depletion, and of adenine nucleotide catabolism in total ischemia in vitro vs. severe ischemia in vivo.

This study was done to compare rates of high energy phosphate (HEP) utilization and depletion, as well as the production and distribution of catabolic products of adenine nucleo tides in dog heart during total ischemia in vitro and severe ischemia in vivo. Both HEP production from anaerobic glycolysis and HEP utilization occurred much more quickly during the firt 15 mmtuet of severe ischemia in vivo than in total ischemia in vitro. HEP utilization exceeded production in both types of ischemia and tissue HEP decreased progressively. Much of the creatine phosphate (CP) was lost within the first 1-3 minutes; adenosine triphosphate (ATP) depletion occurred more slowly than CP and more slowly in vitro than in vivo. ATP was reduced from control contents of 5-6 /imol/g to 1.0 jirool/g by 75 minutes of total ischemia in vitro, but reached a similar level within only 30 minutes of severe ischemia in vivo. HEP utilization and production during ischemia were estimated from the rate of accumulation of myocardial lactate and essentially ceased when the ATP reached 0.4 jimol/g wet weight. At this time, more than 80% of the HEP that had been utilized in ischemia in vivo or in total ischemia in vitro had been derived from anaerobic glycolysis. ATP depletion was paralleled by dephosphorylation of adenine nucleottdeg. The lost nucleotides were recovered stoichiometrically as adenosine, inosine, hypoxantbine, and xanthine in both models of ischemia, a finding which demonstrates that the low collateral flow of severe ischemia allows little washout of nucleosides, bases, or lactate to the systemic circulation. These results Indicate that total ischemia in vitro can be used as a model of severe ischemia in vivo in that the pathways of energy production and depletion and of adenine nucleotide degradation generally are similar. Moreover, the larger quantities of uniformly ischemic tissue and the slower time course of changes make total ischemia well suited to the study of relationships between the metabolic, ftmctional, and structural consequences of ischemic injury, drc