Atrial Electrophysiological Remodelling in a Pre-Obese Mouse Model of Type II Diabetes: Intracellular Recording Studies — ASN Events

Atrial Electrophysiological Remodelling in a Pre-Obese Mouse Model of Type II Diabetes: Intracellular Recording Studies (#467)

Melissa Neo 1 , Wei Wen Lim 1 , Pawel Kuklik 1 , Anand Ganesan 1 , Prashanthan Sanders 1 , David A Saint 1
  1. Centre for Heart Rhythm Disorders, The University of Adelaide, Adelaide, South Australia, Australia

Introduction: Diabetes mellitus (DM) is a risk factor for atrial fibrillation (AF). However, the underlying mechanisms associating the two diseases are unknown. We investigated action potential duration (APD) and restitution curves in a mouse model of human obesity-induced type II diabetes (NONcNZO10/LtJ mice).

Methods: Intracellular action potential recordings were obtained from the isolated left atria of SWR/J mice (control, n=7) and NONcNZO10/LtJ mice (NON, n=7) aged 8-11 weeks. APD at 90%, 50% and 20% of repolarisation was obtained using Chart5 (ADInstruments).

Results: NON mice (24.89 ± 0.68 g) were significantly heavier than their age-matched control mice (23.14 ± 0.40 g) (p=0.046). APD was significantly longer in NON mice at 90% of repolarisation (p<0.0001), and significantly shorter at 20% of repolarisation (p<0.05, see figure) across all pacing cycle lengths. Similarly, APD50 was also significantly shorter (p<0.0001) in NON mice at a pacing cycle length of 400 ms.

Conclusion: Atrial AP parameters were significantly altered in adolescent pre-obese type II diabetic mice. These findings may shed light on how the electrophysiological remodelling induced by type II DM increases susceptibility to AF in the absence of obesity.