title: Energy metabolism of the heart in catecholamine-induced myocardial injury. Concentration-dependent effects of epinephrine on enzyme release, mechanical function, and "oxygen wastage".
abstract: 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 X 10(-4) M (399 +/- 67 mU/g per min, N = 6), but not by cAMP, 5 X 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. Epinephrine-induced enzyme loss was also decreased by halving the perfusate Ca2+ or doubling the perfusate Mg2+ or by verapamil, 2 X 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.
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003402:Creatine Kinase / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000494:pharmacology
chemical_list: D003994:Bucladesine; D000255:Adenosine Triphosphate; D011433:Propranolol; D013806:Theophylline; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D004837:Epinephrine