Lysophosphatidylcholine causes cardiac arrhythmia

Abstract

The precipitation of malignant cardiac arrhythmias after onset of ischemia is well-documented [7]. Although many biochemical and physiological changes were observed during ischemia, the exact cause for disturbances in cardiac rhythm after ischemia remains obscure. Recently, several investigators reported that lysophosphoglycerides were accumulated in the ischemic myocardium [3, 11, 12] of several mammalian species. These lysophosphoglycerides are thought to originate from hydrolytic deacylation of phospholipids [4]. Since lysophosphoglycerides are cytolytic, [13] the accumulation of these lipids in myocardium may be important in the genesis of arrhythmias associated with ischemia. Depression of action potential in isolated cardiac fibers by lysophosphatidylcholine (LPC) further suggests the arrythmogenic nature of these lipids [4]. More recent work showed that LPC and acyl carnitine, another amphiphilic compound, had similar electrophysiological effects on canine Purkinje fibers [5] and the effect might be dependent on a critical micelle concentration [1]. In this communication, we provide direct evidence that perfusion of hamster hearts with a solution containing LPC, the major lysophosphoglyceride in mammalian hearts, causes cardiac arrhythmias as a function of the quantity present in the free form. Exclusively bound lysophosphatidylcholine, associated with serum proteins, is not arrhythmogenic, as has been noted by others [5]. The results indicate also that low concentrations of free lysophosphatidylcholine, simulating those found in ischemic hearts, are arrhythmogenic.