Effects of Palmitoyl Carnitine on Perfused Heart and Papillary Muscle

Abstract

Background: Palmitoyl carnitine accumulation during ischemia causes profound electro physiological changes, resulting in arrhythmias. We studied the electrophysiological and contractile effects of palmitoyl carnitine.

Methods and Results: Extracellular recordings made by using the endocardial unipolar paced evoked response (PER) in isolated perfused rabbit hearts were compared with action potentials (AP) recorded from septal artery perfused rabbit papillary muscle. Left ventricu lar pressure was monitored in isolated hearts. In perfused hearts palmitoyl carnitine (30 μmol/L, 30 minutes) significantly (P < .001) increased the latency of activation (St-R inter val) by 58% ± 8% and reduced repolarization time (R-E interval) by 39% ± 4%. PER duration (St-E interval), was reduced by 30% ± 3%. Palmitoyl carnitine (30 μmol/L) signif icantly (P < .001) decreased resting membrane potential (19 ± 2 mV) of AP, reduced peak amplitude (33.5 ± 8 mV) and rate of rise of phase 0 (41 ± 8 V/s). Significant reductions (P < .001) in the action potential duration 50% (129.4 ± 28 ms) and 90% (139.8 ± 32 ms) were also observed. An initial positive inotropic effect, which declined as irreversible con tracture developed, was also observed. Verapamil (1 μmol/L), nifedipine (1 μmol/L), and caffeine (10 mmol/L) failed to abolish the positive inotropy.

Conclusions: We suggest that palmitoyl carnitine disrupts intracellular calcium homeostasis leading to disturbances in electrical and contractile activity. Its accumulation during myo cardial ischemia could contribute to calcium overloading and initiate lethal arrhythmias.