Abstract
BackgroundType 2 diabetes is associated with abnormal electrical conduction and sudden cardiac death, but the pathogenic mechanism remains unknown. This study describes electrophysiological alterations in a diet-induced pre-diabetic rat model and examines the underlying mechanism.MethodsSprague–Dawley rats were fed either high-fat diet and fructose water or normal chow and water for 6 weeks. The electrophysiological properties of the whole heart was analyzed by in vivo surface ECG recordings, as wells as ex vivo in Langendorff perfused hearts during baseline, ischemia and re-perfussion. Conduction velocity was examined in isolated tissue strips. Ion channel and gap junction conductances were analyzed by patch-clamp studies in isolated cardiomyocytes. Fibrosis was examined by Masson’s Trichrome staining and thin-layer chromatography was used to analyze cardiac lipid content. Connexin43 (Cx43) expression and distribution was examined by western blotting and immunofluorescence respectively.ResultsFollowing 6 weeks of feeding, fructose-fat fed rats (FFFRs) showed QRS prolongation compared to controls (16.1 ± 0.51 (n = 6) vs. 14.7 ± 0.32 ms (n = 4), p < 0.05). Conduction velocity was slowed in FFFRs vs. controls (0.62 ± 0.02 (n = 13) vs. 0.79 ± 0.06 m/s (n = 11), p < 0.05) and Langendorff perfused FFFR hearts were more prone to ventricular fibrillation during reperfusion following ischemia (p < 0.05). The patch-clamp studies revealed no changes in Na+ or K+ currents, cell capacitance or gap junctional coupling. Cx43 expression was also unaltered in FFFRs, but immunofluorescence demonstrated an increased fraction of Cx43 localized at the intercalated discs in FFFRs compared to controls (78 ± 3.3 (n = 5) vs. 60 ± 4.2 % (n = 6), p < 0.01). No fibrosis was detected but FFFRs showed a significant increase in cardiac triglyceride content (1.93 ± 0.19 (n = 12) vs. 0.77 ± 0.13 nmol/mg (n = 12), p < 0.0001).ConclusionSix weeks on a high fructose-fat diet cause electrophysiological changes, which leads to QRS prolongation, decreased conduction velocity and increased arrhythmogenesis during reperfusion. These alterations are not explained by altered gap junctional coupling, Na+, or K+ currents, differences in cell size or fibrosis.
Highlights
Type 2 diabetes is associated with abnormal electrical conduction and sudden cardiac death, but the pathogenic mechanism remains unknown
fructose-fat fed rats (FFFR) and control rats respond differently to ischemiareperfusion To examine if the observed conductance abnormalities predispose FFFRs to cardiac arrhythmias, we evaluated both functional and electrophysiological characteristics of Langendorff perfused hearts, before, during and following 30 min of left anterior descending coronary artery (LAD) occlusion
With the data presented in this paper we demonstrate that FFFRs have QRS prolongation in vivo, as well as decreased conduction velocity ex vivo
Summary
Type 2 diabetes is associated with abnormal electrical conduction and sudden cardiac death, but the pathogenic mechanism remains unknown. This study describes electrophysiological alterations in a diet-induced pre-diabetic rat model and examines the underlying mechanism. Metabolic disorders such as type 2 diabetes and metabolic syndrome are associated with abnormal electrical conduction in the heart, increased risk of cardiac arrhythmias, and sudden cardiac death [1,2,3]. Studies in streptozotocin (STZ) induced type 1 diabetic rats, revealed decreased conduction velocity in the heart at baseline, along with a decreased conduction reserve in response to uncoupling [5, 6]. For STZ induced diabetic rats, gap junction remodeling, seen as altered expression of the major ventricular gap junction protein connexin (Cx43) [7, 8], and/ or Cx43 lateralization [6, 9] are proposed as a potential mechanism for their altered conduction
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
