Dyscholesterolemia Protects Against Ischemia-Induced Ventricular Arrhythmias

Abstract

Background-Hypercholesterolemia protects against ventricular fibrillation in patients with myocardial infarction. We hypothesize that hypercholesterolemia protects against ischemia-induced reentrant arrhythmias because of altered ion channel function. Methods and Results-ECGs

Letter by Baartscheer et al Regarding Editorial, “Matter of Fat: Are Lipids Antiarrhythmic?”

“…2 In our article, we have presented evidence that increased sarcolemmal cholesterol content provides an antiarrhythmic effect mediated through an increased Ca 2+ current and a resulting prolongation of the ventricular action potential.…”

Human electronegative low-density lipoprotein modulates cardiac repolarization via LOX-1-mediated alteration of sarcolemmal ion channels

“…In experimental studies, copper-oxidized LDL has been shown to modify electrophysiological properties of isolated ventricular myocytes of guinea pigs including prolongation of action potential duration, depolarization of resting membrane potential, spontaneous activity, generation of afterdepolarizations, and modification of transmembrane ion currents 18 . In animal studies, hypercholesterolemia has been consistently shown to be associated with action potential prolongation because of enhanced L-type calcium current ( I ca ) 19 , 20 . Thus, it was generally believed that both the exogenous copper-oxidized LDL and the endogenous hypercholesterolemia may alter the electrophysiological phenotypes of cardiomyocytes leading to increased or decreased susceptibility to ventricular tachyarrhythmias in the heart 19 , 20 .…”

Matter of Fat

“…'s 3 study provides data to suggest that the protective effect of dyslipidemia on murine arrhythmia perpetuation does not carryover to protection against arrhythmia initiation (triggers) in the same hearts. Following a MI, cells within the region of infarction are in different stages of depolarization.…”

“…The study of Baartscheer et al 3 in this issue focuses on the effects of changes in the lipid composition of the membrane and ion channel function before the acute effects of ischemia occur. In this study the authors induced regional ischemia in wildtype (WT) controls as well as in two validated dyslipidemic mouse models LDLr-/- and ApoA1-/-.…”

“…'s 3 study provides interesting insight into the immediate protective effect of dyslipidemia on arrhythmia perpetuation induced with programmed ventricular stimulation of LDLr-/- and ApoA1-/- ex-vivo hearts post coronary artery occlusion. The authors propose that patients with dyslipidemia may be protected from sustained ventricular arrhythmias since dyslipidemia prolongs the APD.…”