Energy Metabolism of the Heart in Catecholamine-Induced Myocardial Injury

Concentration-Dependent Effects of Epinephrine on Enzyme Release, Mechanical Function, and “Oxygen Wastage”
  • A. R. Horak
  • L. H. Opie

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 × 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.

Keywords

Oxygen Uptake Coronary Flow Peak Release Pressure Work Enzyme Release 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • A. R. Horak
    • 1
  • L. H. Opie
    • 1
  1. 1.MRC Ischaemic Heart Disease Research Unit, Department of MedicineUniversity of Cape Town and Groote Schuur HospitalCape TownSouth Africa

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