1. Diet-induced pre-diabetes slows cardiac conductance and promotes arrhythmogenesis
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Johannes Pauli Hofgaard, Morten Schak Nielsen, Thomas Hartig Braunstein, Mads Riemann, Christa Funch Jensen, Lars Bo Nielsen, Kirstine Calloe, Lene Nygaard Axelsen, Thomas Jespersen, Ulrik Baandrup, Kristine Boisen Olsen, Niels-Henrik Holstein-Rathlou, Bo Liang, and Emil D. Bartels
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Male ,medicine.medical_specialty ,Patch-Clamp Techniques ,Potassium Channels ,Conduction velocity ,Endocrinology, Diabetes and Metabolism ,Myocardial Ischemia ,Ischemia ,Myocardial Reperfusion ,Fructose ,Arrhythmias ,Diet, High-Fat ,Sodium Channels ,Nerve conduction velocity ,Prediabetic State ,Rats, Sprague-Dawley ,Masson's trichrome stain ,Electrocardiography ,Heart Conduction System ,Fibrosis ,Internal medicine ,medicine ,Animals ,Myocyte ,Myocytes, Cardiac ,Triglycerides ,Gap junctions ,Original Investigation ,business.industry ,Myocardium ,Diabetes ,Gap junction ,Arrhythmias, Cardiac ,medicine.disease ,Myocardial Contraction ,Rats ,Electrophysiology ,Disease Models, Animal ,Endocrinology ,Diabetes Mellitus, Type 2 ,Connexin 43 ,Ventricular fibrillation ,Electrical conduction system of the heart ,business ,Cardiology and Cardiovascular Medicine - Abstract
BACKGROUND: 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.METHODS: Sprague-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.RESULTS: Following 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 CONCLUSION: Six 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.
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