Metabolic and flow correlates of myocardial ischaemia

Seven hundred and twenty three biopsies were obtained from 20 dogs after coronary artery ligation for 5, 30, 45, 60 or 120 min (n = 4 dogs for each group). Paired values for blood flow (radioactive microspheres) and tissue ATP content were obtained for each biopsy and related to the duration of ischaemia. Three states of ischaemic injury could be recognised. In the first, designated as "tolerable" ischaemia, coronary flow was reduced by up to 50%. In this flow band, ATP depletion was relatively small and time-independent. If flow was reduced by 60 to 80%, a state of "critical" ischaemia was identified where ATP depletion was both flow- and time-dependent and, in this relatively narrow range, small changes in flow or duration could result in major changes in ATP depletion. With severe flow reductions of greater than 80%, designated as "lethal" ischaemia, a complex pattern emerged such that with up to 30 min of ischaemia, ATP fell progressively with increasing time and flow deprivation. Between 30 and 45 min ATP depletion accelerated and beyond 45 min the time-dependency disappeared with tissue ATP content remaining relatively constant at a severely depressed level for several hours. All of these results are discussed in the light of earlier proposals (disputed) that tissue injury as expressed by ATP depletion can be predicted by the product of ischaemic duration and flow deprivation.