Relation between coronary artery stenosis and myocardial purine metabolism, histology and regional function in humans

In 54 patients undergoing elective or emergency aortocoronary bypass grafting, angiographic and electrocardiographic changes were studied. Five patients with unstable angina and five patients with evolving myocardial infarction were included. High energy phosphate metabolism and the histologic appearance of the myocardium were analyzed in transmural biopsy specimens acquired at the time of surgery.In patients without anterior infarction on the electrocardiogram, severe stenosis of the left anterior descending coronary artery resulted in a reduction of anterior wall motion that was associated with a partial depletion of the adenylate pool. Mitochondrial function, however, remained intact: the adenosine diphosphate/adenosine triphosphate ratio, the energy charge and the creatine phosphate/adenosine triphosphate ratio were in the normal range. Histologic assessment demonstrated viable myocardium with a high incidence of atrophic cells.In evolving myocardial infarction, 170 minutes of acute coronary artery obstruction resulted in anterior wall akinesia associated with a decrease of the sum of the adenylates to 52% and of creatine phosphate to 16% of their normal value (p < 0.05). The nucleosides accumulated; their major fraction (91%) was inosine. The adenosine diphosphate/adenosine triphosphate ratio increased from 0.14 ± 0.04 to 0.49 ± 0.20 (p < 0.01) and the energy charge decreased from 0.924 ± 0.021 to 0.660 ± 0.169 (p < 0.01). Ultrastructure examination revealed irreversible cell damage in at least the subendocardial layer.These results suggest that the energetic base of reduced contractility due to severe coronary artery stenosis is different from that in acute coronary obstruction: the decrease in contractile function cannot be explained by a reduced oxidative phosphorylation but may be related to an impaired energy utilization at the myofibrillar level, in analogy with the postischemic reperfused stunned myocardium