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Animal ischemia data caution against clinical extrapolation; leaves open human translation of metabolic targets.
Complete global myocardial ischemia or zero coronary arterial flow in dogs results in a series of well-defined changes which begin when the myocardium converts from aerobic to anaerobic metabolism. These processes continue until the myocardium dies. The products of anaerobic metabolism, chiefly glycolytic intermediates, inorganic phosphate, H+, and creatine, are produced intracellularly and accumulate in the tissue. Because the demand for high-energy phosphates (HEP) in the tissue exceeds the supply available from anaerobic glycolysis and HEP reserves, net ATP level declines, approaching zero after 100 min of ischemia at 37 degrees C. At this time, the changes in totally ischemic tissue in vitro are equivalent to those seen in myocytes irreversibly injured by severe ischemia in vivo. During reoxygenation after total ischemia, the resumption of effective contractile activity depends partly on the metabolic changes and degree of myocyte injury sustained during ischemia.
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Jennings et al. (1988) studied this question.
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