Rosiglitazone Attenuates Atrial Structural Remodeling and Atrial Fibrillation Promotion in Alloxan-Induced Diabetic Rabbits

Introduction: The pleiotropic effects of glitazones may favorably affect atrial remodeling. We sought to investigate the effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activator rosiglitazone on atrial structural remodeling and atrial fibrillation (AF) promotion in alloxan-induced diabetic rabbits. Methods: Twenty alloxan-induced diabetic rabbits were randomly divided into two groups (10 animals in each group), namely the diabetic rosiglitazone group (treated with rosiglitazone 2 mg/day/kg for 4 weeks) and the nontreated diabetic group, while 10 additional healthy rabbits served as controls. Moreover, isolated Langendorff-perfused rabbit hearts were used to evaluate atrial electrophysiological parameters and vulnerability to AF, examined by burst pacing. Histological examination was also performed, whereas plasma oxidative stress and inflammatory biomarkers were measured. Results: The duration of induced AF was significantly prolonged in the alloxan-induced diabetic rabbits compared with controls (1.6 +/- 0.4 s vs. 0 s; P < 0.05). Rosiglitazone treatment significantly reduced the duration of induced AF in the treated rabbits (1.6 +/- 0.4 s vs. 1.2 +/- 0.05 s; P < 0.05). Moreover, rosiglitazone attenuated atrial structural remodeling reducing the interatrial activation time (35.4 +/- 12.1 ms vs. 24.2 +/- 10.8 ms, P < 0.05; control 23.3 +/- 10.4 ms) and the atrial interstitial fibrosis as well (collagen volume fraction: 5.6 +/- 3.9% vs. 2.4 +/- 2.1%, P < 0.05; control 1.6 +/- 0.8%). Rosiglitazone increased plasma superoxide dismutase (SOD) activity and, on the other hand, decreased malondialdehyde (MDA), hs-C-reactive protein, and tumor necrosis factor-alpha levels. Conclusion: Rosiglitazone attenuates arrhythmogenic atrial structural remodeling and AF promotion in alloxaninduced diabetic rabbits. Also, it seems to modulate oxidative stress and inflammation in this experimental model.