Two different metabolic responses to ischaemia: inherent variability or artefact?

Guinea pig hearts, perfused with (5-3H) glucose (8 mmol . litre-1) and subjected to 30 min of reduced (6%) coronary flow, exhibited two distinctly different metabolic and electrophysiological responses to ischaemia. In 22 of the 50 hearts studied (Group 1) glucose utilisation declined during ischaemia from 2.5 +/- 0.2 to 1.3 +/- 0.2 mumol . litre-1 . g-1 dry wt. In these hearts, endogenous substrates such as glucogen and triglyceride were mobilised and, although input into glycolysis may have been initially increased through accelerated glycogenolysis, estimated glycolytic flux (1.7 +/- 0.1 mumol hexose . min-1 . g-1 dry wt) remained limited. Instead, there was a large accumulation of the intermediates of glycolysis, an increase in the content of AMP and cAMP and a particularly marked decline in creatine phosphate levels. With subsequent reperfusion, these hearts all fibrillated. In contrast, in the other 28 hearts (Group 2) glucose utilisation (5.1 +/- 0.4 mumol . min-1 . g-1 dry wt) and estimated glycolytic flux (4.1 +/- 0.01 mumol hexose . min-1 . g-1 dry wt) were increased during ischaemia. In these preparations, relatively little glycogen and triglyceride were utilised, and there was less accumulation of glycolytic intermediates. Further, lower levels of AMP and cAMP were observed and creatine phosphate: creatine ratios were better maintained. These hearts did not fibrillate during reperfusion. Thus the variable susceptibility of the myocardium to ischaemic damage, as evidenced by the random incidence of ventricular fibrillation during reperfusion, may have been related to two distinctly different metabolic responses to restricted perfusion.