Energy Metabolism of the Heart in Catecholamine-Induced Myocardial Injury
Epinephrine caused a dose-related release of lactate dehydrogenase (LDH) from the isolated perfused working rat heart. Thus, epinephrine, at 10-8 m, did not increase release of LDH, but at 10-6 m, it gave a peak release of 712 ± 48 mU/g fresh wt. per min (N = 41) 10 min after addition (control: 17 ± 2 mU/g per min, N = 36). The effects of 10-7 m epinephrine (peak release: 159 ± 28 mU/g per min, N = 29) were mimicked by theophylline, 10-3 m. Increased release of LDH was also achieved by dibutyryl cAMP, 5 × 10-4 m (399 ± 67 mU/ g per min, N = 6), but not by cAMP, 5 × 10-4 m. Increased tissue cAMP could be related to the extent of enzyme loss induced by epinephrine or by theophylline. Both tissue cAMP and LDH decreased when propranolol, 10-5 m, was added to epinephrine 10-6 m. Epinephrineinduced enzyme loss was also decreased by halving the perfusate Ca2+ or doubling the perfusate Mg2+ or by verapamil, 2 × 10-7 m, thereby showing a role for Ca2+ entry. However, there was no evidence for excess excitation-coupling with major ATP depletion. Although decreased efficiency of pressure work (“oxygen wastage”) was a graded phenomenon, it was apparent even with epinephrine, 10-8 m. As the epinephrine concentration rose, so did heart rate, coronary flow, oxygen uptake, the degree of “oxygen wastage,” the level of tissue cAMP, and the extent of enzyme release. At 10-7 m epinephrine, the efficiency of pressure work was only 68% of control, but there was no depletion of high-energy phosphate compounds despite marked enzyme loss. Rather, there was a small loss of ATP only at the highest epinephrine concentration (10-6 m) with an increase of phosphocreatine, suggesting that intracellular transfer of energy was impaired. Epinephrine-induced enzyme release and “oxygen wastage” could occur at concentrations below 10-6 m which did not cause detectable depletion of the tissue content of ATP.
KeywordsOxygen Uptake Coronary Flow Peak Release Pressure Work Enzyme Release
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