The mechanism by which ischemic postconditioning reduces reperfusion arrhythmias in rats remains elusive.
Authors:
Journal: Journal of cardiovascular pharmacology and therapeutics
Publication Type: Journal Article
Date: 2009
DOI: 10.1177/1074248408329606
ID: 19461101
Abstract
We have observed that ischemic postconditioning markedly reduces reperfusion-induced ventricular arrhythmias, but whether the mechanism is related to previously described pathways of preconditioning or postconditioning for infarct size reduction is unknown. The purpose of this study was to determine whether known pathways were involved in postconditioning's protective effect on arrhythmias. Anesthetized female rats were subjected to 5 minutes of proximal coronary artery occlusion and 5 minutes of reperfusion. They were either not postconditioned or subjected to 4 cycles of 20 seconds reperfusion, 20 seconds reocclusion before final reperfusion (postconditioned). Electrocardiogram and blood pressure were monitored throughout. Alleged agonists and antagonists to postconditioning representing a number of mechanisms were evaluated. Nonpostconditioned rats treated with the suppressor of the mitochondrial permeability transition pore, cyclosporine A, did not show a reduction in reperfusion-induced ventricular arrhythmias compared to control nonpostconditioned rats. Neither Wortmannin (p13-kinase inhibitor), 5 hydroxydecanoate (selective inhibitor of mitochondrial K(ATP) channel), nor 8-sulfophenyl theophylline (blocker of adenosine receptors) blocked the reduction in ventricular tachycardia of postconditioning. The mechanism by which postconditioning reduces reperfusion-induced ventricular arrhythmias may be independent of known pathways that have been implicated in the infarct sparing effects of preconditioning and postconditioning--including adenosine, mitochondrial K(ATP) channel, mitochondrial permeability transition pore, and p13-kinase-pAKt pathways. Alternative protective pathways may exist to explain the antiarrhythmic effect of postconditioning.
Chemical List
- Mitochondrial Membrane Transport Proteins|||Mitochondrial Permeability Transition Pore