Critical early metabolic changes associated with myocardial recovery or failure after total ischaemia in the rat heart

Abstract

Isolated rat hearts were used to measure tissue levels of the adenine nucleotides plus their degradation products and the 'intracellular' electrolytes after 15 or 25 min of global ischaemia alone and also after 5 or 60 min of reperfusion. Following 15 min of ischaemia, hearts showed near complete recovery of cardiac function (aortic flow rate = 92 +/- 7% of control), but recovery was severely depressed following 25 min of ischaemia (aortic flow rate = 18 +/- 15% of control). Similarly, after 5 min of reperfusion, hearts made ischaemic for 25 min had a reduced tissue content of ATP (10.5 vs 18.9 mumol X g X dry wt), and NAD (4.30 vs 4.75 mumol X g X dry wt) and a 3-4-fold increase in AMP, adenosine and oxypurines, as compared with hearts ischaemic for 15 min. However, the extent of loss of oxypurines during 5 min of reperfusion was essentially similar in both groups (21% vs 18% of total purine pool). After this initial period of reperfusion a significant (p less than 0.01) difference in potassium content was seen between the two groups; hearts which recovered function gained, whilst failing hearts lost, potassium. Changes in the other electrolytes were essentially similar in the two groups of hearts. Extending reperfusion from 5 to 60 min did not change ATP levels in either group but in the functionally depressed group it was associated with a 5-fold increase in calcium and a 30% reduction in potassium, together with a further loss of oxypurines. Thus, loss of nucleotide precursors does not appear to be a critical event in the relatively sudden transition from reversible to irreversible functional injury in ischaemia. There may, however, be a reduction in the activity of the ATP synthesizing processes.