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Title: Basic mechanisms involved in the protection of the ischaemic myocardium. The role of calcium antagonists.
Austin Authors: Nayler, W G
Affiliation: Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 16-May-1991
Publication information: Drugs; 42 Suppl 2(): 21-7
Abstract: A sudden, severe and sustained reduction in coronary blood flow triggers progressive damage to the myocardium, starting with a loss of adenosine triphosphate, creatine phosphate, potassium ions and active tension-generating capacity, and proceeding until the myocytes are swollen, acidotic, incapable of maintaining ionic homeostasis, depleted of the purine precursors needed for energy (as adenosine triphosphate) repletion, and showing signs of structural disorganisation. In addition, the cells become electrically unstable and unable to relax. The early development of raised end-diastolic resting tension probably reflects the early rise in cytosolic Ca++ which occurs in part because of the generation of free radicals. The calcium antagonists can protect against the ischaemia-reperfusion-induced injury, provided they are used prophylactically, and adequate plasma levels are attained. The basis of this protective effect is complex and includes an energy-sparing effect, a slowed loss of adenosine precursors, a slowed rise in cytosolic Ca++, and sometimes, a slowed release of endogenous noradrenaline (norepinephrine). In the case of verapamil, evidence of its protective effect includes reduced creatine kinase release, reduction in infarct size, improved recovery of contractility, maintenance of energy-rich phosphates, preservation of ultrastructure, and maintenance of mitochondrial function. Prophylactic therapy with calcium antagonists has additional advantages in that these agents slow the development of atherogenic plaques, protect the vascular endothelial cells and, in some instances, protect against lipid peroxidation caused by free radicals.
Gov't Doc #: 1718698
Journal: Drugs
Type: Journal Article
Subjects: Calcium.metabolism
Calcium Channel Blockers.metabolism.therapeutic use
Coronary Disease.drug therapy.metabolism
Myocardial Reperfusion Injury.prevention & control
Verapamil.therapeutic use
Appears in Collections:Journal articles

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