Effect of calmodulin antagonists on hypoxia and reoxygenation damage in isolated rabbit hearts
- 1 May 1986
- journal article
- research article
- Published by Springer Nature in Basic Research in Cardiology
- Vol. 81 (3) , 311-325
- https://doi.org/10.1007/bf01907414
Abstract
Summary The effect of calmodulin antagonists trifluoperazine (2.5×10−7 M and 2.5×10−6 M) and R 24571 (10−8 M and 10−7 M) on Langendorff-perfused rabbit hearts subjected to 180 min hypoxia and 30 min reoxygenation was studied. Coronary flow, force of contraction, oxygen consumption and release of lactate, noradrenalin and LDH were measured. Both drugs were found to reduce some of the deleterious consequences of hypoxia, i.e., they caused: 1. marked reduction in the hypoxic LDH release; 2. reduction in hypoxic contracture; 3. increased recovery of active tension, oxygen consumption and coronary flow upon reoxygenation as compared to those in the untreated controls. The drugs prevented reoxygenation-induced LDH release in the drug-pretreated hearts and had no effect when given only during reoxygenation. This suggests that the drugs do not prevent reoxygenation damage as such, but only some changes developing during hypoxia, which make myocardium vulnerable to the reoxygenation damage. Although other interpretations are possible (e.g., the effects are related to the membrane stabilizing action of the drugs), our data are consistent with the hypothesis that a calmodulin-sensitive process is involved in the hypoxia damage of the myocardium.Keywords
This publication has 42 references indexed in Scilit:
- Effects of chlorpromazine on the isolated perfused guinea pig heartGeneral Pharmacology: The Vascular System, 1984
- R 24 571: A potent inhibitor of calmodulin-activated enzymesCell Calcium, 1981
- Effect of calcium on intracellular pHBiochemical and Biophysical Research Communications, 1981
- Cardiac calmodulin and its role in the regulation of metabolism and contractionJournal of Molecular and Cellular Cardiology, 1980
- Calmodulin stimulates human platelet phospholipase A2Biochemical and Biophysical Research Communications, 1979
- Phospholipase A activity of highly enriched preparations of cardiac sarcolemma from hamster and dogJournal of Molecular and Cellular Cardiology, 1978
- -adrenoceptor antagonists and the release of creatine phosphokinase from hypoxic heart muscleCardiovascular Research, 1977
- The metabolism of the anoxic heart after surgical denervation or reserpine pretreatmentJournal of Molecular and Cellular Cardiology, 1973
- Changes in Coronary Flow and ECG in the Isolated Perfused Rat Heart Induced by Phenothiazine DrugsActa Pharmacologica et Toxicologica, 1969
- The influence of some cations on an adenosine triphosphatase from peripheral nervesBiochimica et Biophysica Acta, 1957