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Myocardial impulse propagation is impaired in right ventricular tissue of Zucker Diabetic Fatty (ZDF) rats

DOI: 10.1186/1475-2840-12-19

Keywords: Diabetic cardiomyopathy, Arrhythmia, Lipotoxicity, Conduction velocity, Gap junctions, Type 2 diabetes, Zucker Diabetic Fatty (ZDF) rats

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Abstract:

We used Zucker Diabetic Fatty (ZDF) rats, as a model of type 2 diabetes, and their lean controls Zucker Diabetic Lean (ZDL) rats to investigate CV and its response to the anti-arrhythmic peptide analogue AAP10. Gap junction remodeling was examined by immunofluorescence and western blotting. Cardiac histomorphometry was examined by Masson`s Trichrome staining and intracellular lipid accumulation was analyzed by Bodipy staining.CV was significantly slower in ZDF rats (56±1.9 cm/s) compared to non-diabetic controls (ZDL, 66±1.6 cm/s), but AAP10 did not affect CV in either group. The total amount of Connexin43 (C×43) was identical between ZDF and ZDL rats, but the amount of lateralized C×43 was significantly increased in ZDF rats (42±12 %) compared to ZDL rats (30±8%), p<0.04. Judged by electrophoretic mobility, C×43 phosphorylation was unchanged between ZDF and ZDL rats. Also, no differences in cardiomyocyte size or histomorphometry including fibrosis were observed between groups, but the volume of intracellular lipid droplets was 4.2 times higher in ZDF compared to ZDL rats (p<0.01).CV is reduced in type 2 diabetic ZDF rats. The CV disturbance may be partly explained by increased lateralization of C×43, but other factors are likely also involved. Our data indicates that lipotoxicity potentially may play a role in development of conduction disturbances and arrhythmias in type 2 diabetes.Diabetes is a major risk factor for sudden cardiac death and ventricular tachy-arrhythmias are suspected to be the predominant mechanism [1]. The prevalence of ventricular arrhythmias is increased in patients with diabetes and although ischemia is suspected to be an important trigger, the increased risk is independent of co-morbidities like coronary heart disease or heart failure [2,3].The electrocardiogram (ECG) of the diabetic heart is often characterized by a prolonged QT interval, reflecting an increase in action potential duration. In support of this, both the IKto- and delayed rec

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