ALTERING MOLECULAR MECHANISMS TO PREVENT SUDDEN ARRHYTHMIC DEATH

Trials of drug treatment for prevention of sudden arrhythmic death hav e been disappointing, perhaps because suppressive therapy with arrhyth mic agents fails to address the mechanisms leading; to electrophysiolo gical failure. We propose that preventive treatment should pay more at tention to molecular mechanisms responsible for the progression of car diac disease to electrophysiological failure. Most sudden cardiac deat hs occur in people with atherogenic dyslipidaemias. Our hypothesis is that the pathogenic molecular mechanisms of dyslipidaemias contribute directly to arrhythmogenesis. Proinflammatory-prothrombotic lipid-deri ved mediators that may play a part in arrhythmogenesis include phospho lipids and leucotrienes acting through the platelet-activating-factor and peroxisome proliferator-activated-receptor pathways. There are dru gs available to test the hypothesis of dyslipidaemias-specific prevent ion of electrophysiological failure.