Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Exp Physiol. 2011 Aug;96(8):778-89. doi: 10.1113/expphysiol.2011.057885. Epub 2011 Jun 10.
Rosiglitazone, a peroxisome proliferator-activated receptor γ agonist, has been used to treat type 2 diabetes. Despite debates regarding its cardioprotection, the effects of rosiglitazone on cardiac electrophysiology are still unclear. This study determined the effect of rosiglitazone on ventricular fibrillation (VF) incidence, VF threshold (VFT), defibrillation threshold (DFT) and mitochondrial function during ischaemia and reperfusion. Twenty-six pigs were used. In each pig, either rosiglitazone (1 mg kg(-1)) or normal saline solution was administered intravenously for 60 min. Then, the left anterior descending coronary artery was ligated for 60 min and released to promote reperfusion for 120 min. The cardiac electrophysiological parameters were determined at the beginning of the study and during the ischaemia and reperfusion periods. The heart was removed, and the area at risk and infarct size in each heart were determined. Cardiac mitochondria were isolated for determination of mitochondrial function. Rosiglitazone did not improve the DFT and VFT during the ischaemia-reperfusion period. In the rosiglitazone group, the VF incidence was increased (58 versus 10%) and the time to the first occurrence of VF was decreased (3 ± 2 versus 19 ± 1 min) in comparison to the vehicle group (P < 0.05). However, the infarct size related to the area at risk in the rosiglitazone group was significantly decreased (P < 0.05). In the cardiac mitochondria, rosiglitazone did not alter the level of production of reactive oxygen species and could not prevent mitochondrial membrane potential changes. Rosiglitazone increased the propensity for VF, and could neither increase defibrillation efficacy nor improve cardiac mitochondrial function.
罗格列酮是一种过氧化物酶体增殖物激活受体 γ 激动剂，用于治疗 2 型糖尿病。尽管关于其心脏保护作用存在争议，但罗格列酮对心脏电生理学的影响仍不清楚。本研究旨在确定罗格列酮对缺血再灌注期间室颤（VF）发生率、VF 阈值（VFT）、除颤阈值（DFT）和线粒体功能的影响。使用 26 头猪。每头猪静脉注射罗格列酮（1mg/kg）或生理盐水 60 分钟。然后结扎左前降支冠状动脉 60 分钟，以促进再灌注 120 分钟。在研究开始时和缺血及再灌注期间测定心脏电生理参数。取出心脏，确定每个心脏的危险区和梗死面积。分离心脏线粒体以测定线粒体功能。在缺血再灌注期间，罗格列酮并未改善 DFT 和 VFT。与载体组相比，罗格列酮组 VF 发生率增加（58%比 10%），VF 首次发生时间缩短（3±2 分钟比 19±1 分钟）（P<0.05）。然而，罗格列酮组的梗死面积与危险区的相关比例明显降低（P<0.05）。在心脏线粒体中，罗格列酮并未改变活性氧的产生水平，也不能防止线粒体膜电位的变化。罗格列酮增加了 VF 的易发性，不能增加除颤效果，也不能改善心脏线粒体功能。
