Abstract
Introduction: Due to anti-inflammatory properties of pioglitazone, a peroxisome proliferator-activated receptor (PPAR)-g activator, it might exert beneficial effects on diabetesrelated atrial remodeling. Objectives: We aimed to investigate the potential effects of pioglitazone, a peroxisome proliferator-activated receptor (PPAR)-g activator, on atrial remodeling and atrial fibrillation (AF) promotion in alloxan-induced diabetic rabbits. Methods: 72 alloxan-induced diabetic rabbits were randomly divided into three groups (n1⁄424 for each): diabetic pioglitazone treatment A group (DPA group, 4mg/day/kg), diabetic pioglitazone treatment B group (DPB group, 8mg/day/kg) and diabetic group (DM group), 24 healthy rabbits served as controls. 8 rabbits in each group were respectively used to electrophysiological and histological study, patch-clamp study and western blotting analysis. 8 rabbits in each groupweremonitored hemodynamics and recorded SBP, DBP and LVEDP and underwent transthoracic echocardiographic examination. After 8-week treatment, isolated Langendorff perfused rabbit hearts were used to evaluate atrial electrophysiological parameters and vulnerability to AF which examined by burst and S1S2 pacing. CVF was calculated by Sirius-Red (SR) staining.Whole-cell patch-clamp technique was used tomeasure APD and atrial ionic currents (ICaL and INa). Western-blot analysis was applied to assess atrial protein expression of ERK2, pERK, TGFb1, TLR4, NF-kB p50 and HSP70 in left atrial tissue. Results: LAD, IVST and PWT were significantly increased in DM group compared with controls, which were markly reduced by pioglitazone. SBP and DBP of DPI group were significantly lower than DM group (P<0.05). IACT and AERPD were prolonged and AF inducibility was increased in DM group (6/8 vs. 1/8, P<0.05) compared with controls, which were markly reduced by pioglitazone. Pioglitazone attenuated atrial structural remodeling, with significant reductions in CVF. APD90 and APD50 were prolonged in DM group (P<0.05 vs. control), the densities of INa were reduced and the densities of ICaL were increased in DM group (P<0.01 vs. control), which were attenuated by pioglitazone. Western-blot analysis revealed DM increased expression of pERK, TGF-b1, TLR4, NF-kB p50 and HSP70, which were reduced by pioglitazone. Conclusion: Pioglitazone prevented DM-related arrhythmogenic atrial remodeling and reduced vulnerability to AF, which may be due to its anti-inflammatory and anti-oxidative characteristics. Disclosure of Interest: None Declared
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