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On the Mechanism of Action of the Antianginal Drug Nonachlazine on Ischemic Myocardium

  • N. V. Kaverina
  • A. I. Turilova
  • Yu. B. Rozonov
  • T. N. Azvolinskaya
  • S. A. Kryzhanovsky

Abstract

The activity of a new antianginal drug, nonachlazine, synthetized in the Institute of Pharmacology, Academy of Medical Sciences of the USSR, has been demonstrated using model myocardial ischemias on anesthetized dogs and conscious cats. Antianginal activity was evaluated by ECG, epicardial electrogram, lactate level, and lactate/pyruvate ratio in the venous blood flowing from the ischemic myocardial area. The study of the cardiotropic effect of nonachlazine provided the following findings: (1) nonachlazine enhances ino- and chronotropic functions of the heart via stimulation of its ß-adrenergic receptors; (2) nonachlazine’s positive chronotropic effect is substantially less marked than the inotropic one; (3) nonachlazine decreases the intensity of chronotropic reactions of the heart induced by isopreterenol. Biochemical analysis showed that in addition to its activation of oxidative phosphorylation, the ability of nonachlazine to stimulate glycogenolysis is also of importance in the development of its antianginal effect. This conclusion has been suggested by the following: (1) in acute myocardial ischemia, nonachlazine decreased lactate level and increased ATP level up to the norm; (2) at day 3 after ligation of the coronary artery, nonachlazine did not change lactate content, increased ATP and NAD, and decreased NADH2; (3) in experiments on rabbit myocardial mitochondria in vivo and in vitro nonachlazine was found to stimulate oxidative phosphorylation; (4) nonachlazine was found capable of increasing the norepinephrine level and of increasing Phosphorylase a activity and the rate of glycogenolysis.

Keywords

Myocardial Contractility Ischemic Area Acute Myocardial Ischemia Chronic Ischemic Heart Disease Antianginal Drug 
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

  • N. V. Kaverina
    • 1
  • A. I. Turilova
    • 1
  • Yu. B. Rozonov
    • 1
  • T. N. Azvolinskaya
    • 1
  • S. A. Kryzhanovsky
    • 1
  1. 1.Institute of PharmacologyAcademy of Medical Sciences of the USSRMoscowUSSR

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