Conduction abnormalities in metabolically stressed CD36 deficient mouse

Abstract

CD36 facilitates myocardial uptake of fatty acids (FA), and has recently been shown to be involved in the regulation of intracellular Ca2+ dynamics in both non‐electrically excitable cells and cardiomyocytes. The heart derives the majority of its energy from FA oxidation and during fasting as glucose utilization diminishes, the heart has an even greater reliance on FA. We investigated whether CD36 dysfunction would accelerate metabolic changes during fasting (18 hrs) that would lead to electrophysiological abnormalities. Conscious non‐anesthetized wild type (WT) (n=5) and CD36 knock out (CD36 KO) (n=5) mice were placed in a restraining device to obtain a baseline ECG before and after fasting. Following fasting, hearts were excised, Langendorff perfused, and subjected to several pacing protocols while being optically mapped. Before fasting, RR, PR, and QTc values were not significant (NS) (p>.05) between groups. After fasting, WT mice displayed a NS increase in RR (75.7 ± 1.0 to 85.4 ± 2.9 ms) and PR (32.8 ± 0.9 to 36.2 ±0.9); whereas, CD36 KO mice showed a significant increase in RR (78.2 ± 1.2 to 120 ± 7.5 ms) and PR (35.9 ±0.9 to 58.7 ± 3.8). CD36 KO mice exhibited a significant increase in the effective refractory period of the atrioventricular (AV) node, ventricular action potential duration, cycle length with which Wenchebach block was observed, and a NS increase in AV‐delay.This work was supported by NIH Grants P01‐HL057278, R01 DK33301.