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Streptozotocin-induced type I diabetes mediates structural and electrophysiological changes in the rat atria: A substrate for atrial fibrillation

M. Neo, W.W. Lim, D.H. Lau, P. Sanders and D.A. Saint, Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, SA 5000, Australia.

Background and Aims: Diabetes is an independent risk factor for atrial fibrillation (AF). Although research on type II diabetes-related cardiovascular disease is well established, the electrophysiological impact of type I diabetes (T1DM) is less well understood.

Methodology: Zucker lean rats (3 months) were subjected to an i.p injection of saline (control, n=10) or 30mg/kg Streptozotocin (T1DM, n=10). Following a 3 month period the animals were sacrificed for experiments. The atria were excised and placed with the epicardial surface in contact with a 9 × 10 multi-electrode array (0.5mm inter-electrode spacing). A 100MΩ aluminosilicate microelectrode was inserted into the endocardial surface during a standard S1-S2 pacing protocol to simultaneously record intracellular action potentials. Action potential duration (APD) at 90%, 50% and 20% of repolarisation, effective refractory period (ERP), body weight, blood glucose levels and blood pressure measurements were obtained. Post-experiments, tissues were weighed and stored for hematoxylin and eosin staining to determine cardiomyocyte size.

Results: No significant differences were found in body weight (control 353.8 ± 4.5, T1DM 373.4 ± 8.5, P = 0.07) and chamber weights (control vs T1DM all chambers P > 0.05) between groups. In T1DM animals, fasting blood glucose (control 13.7 ± 1.3mmol/L, T1DM 18.5 ± 1.2mmol/L, P = 0.04) and blood pressure levels were elevated (control 129.4mmHg ± 5.7, T1DM 137.5 ± 3.7mmHg, P = 0.04). While AP repolarisation parameters were significantly prolonged across all pacing cycle lengths in both atria for T1DM animals (see table), the reverse occurred for the ERP; there was a shortening of the ERP in both atria in T1DM animals compared to control animals (LA: control 62.4 ± 1.3ms, T1DM 53.2 ± 1.0ms, P < 0.0001; RA: control 58.8 ± 1.2ms, T1DM 50.6 ± 1.1ms, P <0.0001). Cardiomyocytes were also found to be larger for both atria in the T1DM animals (LA: control 8.8 ± 0.1μm, T1DM 12.0 μm, p < 0.0001; RA: control 8.3 ± 0.1μm, T1DM 11.2 ± 0.3μm, P < 0.0001).

Conclusion: Our results suggest that T1DM may have an important role in mediating atrial structural and electrophysiological changes to provide a potentially vulnerable substrate in favour of increased predisposition to AF.