NORMAL DEVELOPMENT OF CONDUCTION VELOCITY IN RATS IS PREVENTED BY FRUCTOSE-FAT FEEDING

Background: Diabetes and metabolic syndrome causes cardiac electrical abnormalities that increase the risk for arrhythmias and sudden death. We have established fructose-fat fed rats (FFFRs) as a prediabetic model, which after 6 weeks of feeding exhibit intramyocardial lipid accumulation, decreased cardiac conduction velocity (CV), and increased risk of ventricular fibrillation following ischemia–reperfusion. CV slowing was not explained by changes in Naþ, Kþ, or gap junction channel function; however, CV may be altered by a depolarized resting membrane potential (RMP). Therefore, the aim of this study was to investigate the time dependence of diet-induced cardiac lipid accumulation, CV disturbances, and changes in RMP and action potential (AP) morphology. Methods: Four-week-old male Sprague-Dawley rats were fed ad libitum with either normal chow or a diet consisting of 60% fat in the chow and 10% fructose in the drinking water. After 1, 3, and 6 weeks of feeding, we measured cardiac CV in right ventricular tissue strips with extracellular electrodes, AP morphology, and RMP using intracellular microelectrodes, and triglyceride content by thin layer chromatography. Results: CV increased from 68.5 0.24 cm/s to 77.7 0.23 cm/s from 1 to 6 weeks in control rats, whereas FFFRs failed to increase CV during the same period (68.9 0.23 cm/s after 1 week vs 67.9 0.23 cm/s after 6 weeks). Intramyocardial triglyceride levels were already significantly higher in FFFRs compared to controls, after 3 weeks of feeding, a time point when CV was not significantly different between controls and FFFRs (70.5 0.15 cm/s vs 70.3 0.20 cm/s). RMP and AP morphology were not different between the 2 groups at any point, except for time to 20% repolarization (APD20), which was significantly longer for FFFRs after 6 weeks (5.69 0.33 ms vs 4.62 0.43 ms). Conclusions: Rats on normal chow increase CV between 1 and 6 weeks of feeding (approximate age 5–6 and 10–11 weeks, respectively), whereas fructose-fat feeding prevents CV development. Lipid accumulation is already present after 3 weeks of fructose-fat feeding, preceding CV slowing. CV slowing could not be explained by changes in RMP or AP upstroke velocity.