Effect of exogenous fatty acids on reperfusion arrhythmias in isolated working perfused hearts.
Exogenous fatty acids may promote arrhythmias during ischemia and reperfusion, perhaps by increasing myocardial concentrations of long-chain acylcarnitines. We therefore studied the effects of high concentrations of fatty acids on reperfusion arrhythmias and acylcarnitine accumulation in isolated working rat hearts subjected to regional ischemia and reperfusion. Hearts were perfused with buffer containing 3% albumin, 5.9 mM K+, and either 11 mM glucose or 11 mM glucose plus 1.2 mM palmitate. After 15 min of aerobic work, the left anterior descending artery was reversibly ligated for 10 min and released, and the hearts were subsequently reperfused for 3 min. Although ischemic zone acylcarnitine accumulation after reperfusion was significantly greater in glucose plus palmitate-perfused hearts (247 +/- 149 vs. 717 +/- 176 nmol/g dry wt in glucose- vs. palmitate-perfused hearts, respectively), no significant differences in the incidence (67 vs. 44%) or duration (95 +/- 17 vs. 56 +/- 17 s) of ventricular fibrillation (VF) were seen in glucose or glucose plus palmitate hearts, respectively. Because low K+ concentration ([K+]) has been reported to increase reperfusion arrhythmias in similar models, we reduced perfusate [K+] to 4.0 mM. This significantly increased the incidence and duration of VF in hearts perfused with glucose alone but had no effect in palmitate-perfused hearts. We conclude that acylcarnitine accumulation is not arrhythmogenic in this model and that fatty acids may actually have antiarrhythmic effects if exogenous [K+] is low.
Davies
N J
NJ
Department of Medicine, University of Alberta, Edmonton, Canada.
Lovlin
R E
RE
Lopaschuk
G D
GD
D000818:Animals; D003326:Coronary Circulation; D003331:Coronary Vessels; D004347:Drug Interactions; D005227:Fatty Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008026:Ligation; D008297:Male; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014693:Ventricular Fibrillation / Q000503:physiopathology*
D005227:Fatty Acids; D011188:Potassium