Objective We investigated the underlying mechanisms caused by pioglitazone on atrial structural remodelling and electrical remodelling in alloxan-induced diabetic rabbits.
Methods 96 rabbits were divided into CN group, DM group, DPG group and DPI group. Isolated Langendorff-perfused rabbit hearts were used to measure electrophysiological parameters and vulnerability to AF. Histopathologic examinations were performed to identify the fibrosis of left atria. Western-Blot was applied to assess protein expressions of ERK, pERK, TGF-β, TLR4, NF-kB p50 and TNF-α.
Results (1) 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). (2) IACT and AERPD were prolonged and AF inducibility was increased in DM group (P < 0.05) compared with controls, which were markly reduced by pioglitazone. (3) Pioglitazone attenuated atrial structural remodelling, with significant reductions in CVF. (4) Western-blot revealed DM increased protein expressions of pERK, TGF-β, TLR4, NF-kB p50 and TNF-α, which were reduced by pioglitazone.
Conclusions Pioglitazone has certain antagonist activity on atrial structural remodelling and electrical remodelling in diabetic rabbits, which resulting in reversal effect on inducibility of DM-related AF.