Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9586
Title: The molecular basis for the use of calcium antagonists in ischaemic heart disease.
Authors: Nayler, W G
Affiliation: Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Issue Date: 16-May-1992
Citation: Drugs; 43 Suppl 1(): 21-7
Abstract: Calcium antagonists are useful for the management of patients with ischaemic heart disease, particularly when used prophylactically. At the cellular level, these drugs act primarily by limiting calcium ion (Ca++) entry through the voltage-sensitive Ca(++)-selective channels, an effect that contributes markedly to their 'energy sparing' properties. However, the long term use of these drugs has additional advantages, particularly with respect to their ability to slow Ca(++)-dependent processes involved in the formation of atherogenic lesions, partially antagonise the effects of the raised levels of circulating endothelin-1 encountered during ischaemia-induced heart failure and hypertension, and trap and immobilise oxyradicals. Prolonged episodes of ischaemia result in an irreversible loss of homeostasis with respect to Ca++. However, the increase in myocardial cytosolic Ca++ caused by relatively short periods of ischaemia is small, reversible, and markedly attenuated by the prophylactic use of calcium antagonists. In the isolated, perfused rat heart, verapamil pretreatment produces statistically significant inhibition of the increase in cytosolic Ca++ during 20-minute global ischaemia. This stereospecific effect is associated with a decrease in the rise in total tissue Ca++ during reperfusion and amelioration of the adenosine triphosphate depletion caused by ischaemia. In general, discussion relating to the molecular basis of the use of calcium antagonists in the management of patients with ischaemic heart disease needs to take into account the duration of the ischaemic event, the workload on the myocardium, the need for prophylactic therapy, and the presence of exacerbating factors such as atherosclerosis and tobacco smoking. The early rise in cytosolic Ca++, the source of which remains uncertain, appears to be an important focus for anti-ischaemic drug therapy.
Internal ID Number: 1378784
URI: http://ahro.austin.org.au/austinjspui/handle/1/9586
URL: http://www.ncbi.nlm.nih.gov/pubmed/1378784
Type: Journal Article
Subjects: Adenosine Triphosphate.metabolism
Animals
Calcium.metabolism
Coronary Disease.metabolism
Magnetic Resonance Spectroscopy
Male
Myocardial Reperfusion
Myocardium.metabolism
Phosphocreatine.metabolism
Rats
Rats, Inbred Strains
Verapamil.pharmacology
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.