The pathophysiological basis of arrhythmogenesis in myocardial ischemia and reperfusion: possible target for intervention.
Regional ischemia and reperfusion alter the homeostasis of many substances in the myocardium. Which, if any play a role as pathophysiological progenitors of the associated arrhythmias? The key questions which must be answered in relation to each are: (i) is the presence of the substance sufficient to account for arrhythmogenesis and (ii) is the presence of the substance necessary for arrhythmogenesis to occur? Although there are many candidates for the role of pathophysiological progenitor, and although there is much evidence in support of a role for various of these, the evidence is largely circumstantial. Some of this evidence is reviewed here. I am of the view that new models must be developed if unequivocal data are to be derived. An example which may be of value in this regard is the newly developed rabbit dual perfusion model. The technical aspects of this model are described herein. Using this model I have examined the role of one prospective pathophysiological progenitor of arrhythmogenesis, K+, the intra-extracellular homeostasis of which is disturbed by ischemia and reperfusion in a manner related on a temporal basis with development of susceptibility to arrhythmogenesis. The article concludes with some speculation on possible future research directions.
Curtis
M J
MJ
Department of Pharmacology, King's College University, London, England.
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D002395:Catecholamines / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D005609:Free Radicals; D006801:Humans; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D011188:Potassium / Q000502:physiology; D011817:Rabbits
D002395:Catecholamines; D005609:Free Radicals; D000804:Angiotensin II; D000242:Cyclic AMP; D011188:Potassium