Poster Presentation 6th Australian Health and Medical Research Congress 2012

Effects of High Fat Diet on Atrial Electrophysiological Remodelling in Type II Diabetes: Electrophysiological Mapping Studies in a Pre-obese Mouse Model (#465)

Wei Wen Lim 1 , Melissa Neo 1 , Pawel Kuklik 1 , Anand Ganesan 1 , David Saint 1 , Prashanthan Sanders 1
  1. Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, SA, Australia

Introduction: Both diabetes mellitus (DM) and atrial fibrillation (AF) are burgeoning epidemics affecting millions worldwide. The relationship between DM and AF remain inconclusive, with equivocal results. Furthermore, the association between obesity in type 2 diabetic patients and the development of AF remains unknown. This study sought to characterize left atria electrophysiological properties in pre-obese NONcNZO10/LtJ (NON) mice, a mouse model of human obesity-induced type 2 diabetes. NON mice have been previously characterized to be pre-obese and hyperglycaemic by 8 weeks of age and a moderately obese state with insulin resistance at 13 weeks1 .

Methods: NON mice (n=13) and SWR/J (control) mice (n=13) were fed either normal or high fat (HF) chow post-weaning. Mice aged 8-11 weeks were anesthetised and the left atria excised and placed on a custom-made micro-electrode array (25 electrodes with 0.5mm inter-electrode spacing). Effective refractory period (ERP) was measured using standard extra-stimulus pacing and conduction velocity (CV) and conduction heterogeneity index (CHI) were subsequently analysed offline.

Results: NON mice body weights were moderately but significantly greater than controls (p<0.05). ERP distribution was not significantly changed in NON mice (p=NS). Additionally, NON mice displayed increased CHI but decreased CV comparing to controls (both p<0.001). Finally, high fat diet resulted in significantly slower CV in NON mice compared to SWR mice (P<0.05).

Conclusion: Pre-obese hyperglycaemic mice demonstrated normal refractoriness, but slower and heterogeneous conduction in the left atria. High fat diet resulted in exacerbated reduction in atrial conduction velocity. These electrophysiological changes, if seen in diabetic patients, may explain the occurence of AF in this population.

  1. Cho Y.R. et al. (2007) Hyperglycemia, maturity-onset obesity, and insulin resistance in NONcNZO10/LtJ males, a new mouse model of type 2 diabetes. Am J Physiol Endocrinol Metab 293: E327-E336.