Ischemic, genetic and pharmacological origins of cardiac arrhythmias: The contribution of the Quebec Heart Institute

Abstract

Research in the field of basic electrophysiology at the Quebec Heart Institute (Laval Hospital, Quebec City, Quebec) has evolved since its beginning in the 1990s. Interests were focused on cardiac arrhythmias induced by drugs, allelic variants and metabolic factors produced during ischemia. The results have contributed to the creation of new standards in drug development, more specifically, testing all new drugs for their potential effects on cardiac potassium currents, which could produce life-threatening proarrhythmic effects. In a French-Canadian population, three heterozygous single nucleotide polymorphisms in hK(v)1.5, a gene encoding for a major atrial repolarizing current, were found. These variants affect the expression level of the hK(v)1.5 channel and change the inactivation process in the presence of its accessory beta subunit. Because these effects could shorten atrial action potential, their presence was tested in postcoronary bypass patients and a higher prevalence was found in patients with postoperative atrial fibrillation. Finally, three potentially proarrhythmic factors characteristic of ischemia were identified: pH decrease; oxygen free radicals, which both increase the flow of K(+) ions through human ether-a-go-go-related gene and hK(v)1.5, producing a reduction in action potential duration, frequently leading to cardiac arrhythmias; and lysophosphatidylcholine, a metabolite involved in the production of cardiac arrhythmias early during ischemia that was shown to be a major cause of electrical uncoupling. Over the past decade, the Quebec Heart Institute has provided a significant amount of original data in the field of basic cardiac electrophysiology, specifically concerning arrhythmias originating from pharmacological agents, genetic background and cardiac ischemia.