title: Altering molecular mechanisms to prevent sudden arrhythmic death.
abstract: Trials of drug treatment for prevention of sudden arrhythmic death have been disappointing, perhaps because suppressive therapy with arrhythmic agents fails to address the mechanisms leading to electrophysiological failure. We propose that preventive treatment should pay more attention to molecular mechanisms responsible for the progression of cardiac disease to electrophysiological failure. Most sudden cardiac deaths occur in people with atherogenic dyslipidaemias. Our hypothesis is that the pathogenic molecular mechanisms of dyslipidaemias contribute directly to arrhythmogenesis. Proinflammatory-prothrombotic lipid-derived mediators that may play a part in arrhythmogenesis include phospholipids and leucotrienes acting through the platelet-activating-factor and peroxisome proliferator-activated-receptor pathways. There are drugs available to test the hypothesis of dyslipidaemias-specific prevention of electrophysiological failure.
authors.affiliation: Texas Arrhythmia Institute, Houston 77030, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Henry
authors.forename: A
authors.initials: A
authors.lastname: Pacifico
mesh_terms: D001145:Arrhythmias, Cardiac / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D016207:Cytokines / Q000037:antagonists & inhibitors; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors / Q000037:antagonists & inhibitors
chemical_list: D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; C039351:platelet activating factor receptor