Mechanism of arrhythmias induced by palmitylcarnitine in guinea pig papillary muscle.
Long chain acyl carnitines, intermediates of free fatty acid metabolism, have been implicated in malignant arrhythmias occurring during myocardial ischaemia. To investigate the mechanism of arrhythmia induced by these compounds the electrophysiological effects of palmitylcarnitine (30, 100 and 300 mumol.litre-1) on guinea pig papillary muscles was examined using the microelectrode technique. Palmitylcarnitine caused a time and concentration dependent shortening of action potential duration, with an increase in both developed and resting tension. After attaining the peak value of developed tension, delayed afterdepolarisations and/or aftercontractions were observed in three out of eight muscles on exposure to 100 mumol.litre-1 palmitylcarnitine and in all 13 muscles on exposure to 300 mumol.litre-1, while arrhythmia occurred in one out of eight muscles and in seven out of 13 muscles during these exposures. The amplitude and the coupling interval of delayed afterdepolarisations were dependent on basic cycle length. Delayed afterdepolarisations, aftercontractions and arrhythmias were completely abolished by ryanodine (1 mumol.litre-1). Though low Ca2+ (0.1 mmol.litre-1) abolished these activities, verapamil (4 and 10 mumol.litre-1) did not suppress them. Palmitylcarnitine (300 mumol.litre-1) shortened action potential duration to the same degree during metabolic block of either oxidative phosphorylation or glycolysis as it did in muscles exposed to oxygenated Krebs solution. Under these conditions, delayed afterdepolarisation and/or aftercontractions appeared in all muscles. We conclude that palmitylcarnitine could cause Ca2+ overload and trigger activity due to delayed afterdepolarisations and could act on the cell membrane independently of cardiac metabolism. We suggest that palmitylcarnitine is a factor in arrhythmogenesis during myocardial ischaemia.
Sakata
K
K
Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
Hayashi
H
H
Kobayashi
A
A
Yamazaki
N
N
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D002331:Carnitine / Q000031:analogs & derivatives*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects* / Q000503:physiopathology
D010172:Palmitoylcarnitine; D002331:Carnitine