Metabolism of infarcted heart muscle during tissue repair

Abstract

The metabolism of infarcted canine heart muscle was studied by examining the enzyme profile of infarcted and normal tissue; oxidative and glycolytic metabolism, as expressed in ATP and lactate levels of the infarcted muscle; and lipid synthesis and fatty degeneration of the infarcted muscle. The activities of heart muscle enzymes were assayed during tissue repair following experimental myocardial infarction. The activities of 10 enzymes were determined in normal heart muscle and in the center and periphery of infarcted muscle. A significant increase in hexosemonophosphate (HMP)-shunt activity was observed in infarcted tissue 5 hours after infarction. the activities of glucose-6-phosphate dehydrogenase (g-6-PDH) and 6-phosphogluconate dehydrogenase (6-PGDH) increase 31–34-fold 10 days after infarction. In contrast to increased activity of the HMP-shunt, there was a rapid decline in oxidative and glycolytic enzyme activities in infarcted tissue. Oxidative enzymes reached the lowest level in center of infarcted tissue 10 days after infarction with 8 to 13 per cent of control activities. Glycolytic enzymes showed a significant fall in activities with the greatest diminution in activity of aldolase to 14 per cent of control but a relatively smaller fall in glyceraldehyde phosphate dehydrogenase (GAPDH) activity. The increased activity of the HMP-shunt in infarcted tissue was also expressed in the relative oxidation of glucose-1-C 14 and glucose-6-C 14 to C 14 o 2 . The diminution in oxidative metabolism was also expressed in a marked fall (85 to 90 per cent decrease) in adenosine triphosphate (ATP) content of the infarcted tissue, and a significant rise in lactate content two days after infarction. ten days after coronary occlusion the cellular ATP level increased again with a parallel decrease in lactate content. The incorporation of acetate-1-C 14 into lipids was significantly increased in both infarcted and uninfarcted areas of the injured muscle, compared to normal heart muscle without coronary occlusion. The distribution of labeled acetate in the lipid fractions indicated a marked increase in triglyceride formation in the infarcted tissue. The rate of fatty acid and glyceride synthesis was found to be regulated by the atp level, stimulated at low ATP levels (1 to 2 mM) but markedly inhibited at physiological ATP levels (5 to 6 mM). The conditions most favorable for lipid synthesis in cardiac muscle are those of a hypoxic or ischemic muscle with diminished ATP level.