Expression of uncoupling protein-2 remains increased within hibernating myocardium despite successful coronary artery bypass grafting at 4 wk post-revascularization.
Expression of uncoupling protein-2 remains increased within hibernating myocardium despite successful coronary artery bypass grafting at 4 wk post-revascularization.
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尽管在血运重建后 4 周成功进行了冠状动脉旁路移植术，但冬眠心肌内解偶联蛋白 2 的表达仍然增加。
DOI：
10.1016/j.jss.2014.08.003
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Kelly,RosemaryF
中科院分区：
文献类型：
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作者：
Holley,ChristopherT;Duffy,CaylaM;Butterick,TammyA;Long,EricK;Lindsey,MeganE;Cabrera,JesúsA;Ward,HerbertB;McFalls,EdwardO;Kelly,RosemaryF
研究背景我们在猪冬眠心肌模型中发现线粒体解偶联蛋白-2（UCP-2）表达增加。虽然UCP-2减少了氧化应激，但它可以促进电子传递链的无效性。在这项研究中，我们测试了UCP-2是否仍然增加，在再血管化HM（RHM）后冠状动脉旁路移植术（CABG）。MethodsSeven猪进行了开胸术与左前降支动脉（LAD）上的缩窄器的位置。12周后，将左乳内动脉移植物置于LAD远端。CABG术后4周，计算机断层扫描血管造影记录了通畅的移植物和功能。在终末研究中，在高剂量多巴酚丁胺期间评估LAD和远端区域的血流，并从两个区域分离线粒体进行分析。结果在多巴酚丁胺灌注期间，与远端区域相比，RHM表现出较低的血流量（2.44 ± 0.23vs3.43 ± 0.30 mL/min/g;P< 0.05）和减少的壁增厚（33 ± 9%vs52 ± 13%;P< 0.05）。RHM的呼吸控制指数较低（3.7 ± 0.3versus4.3 ± 0.4;P< 0.05），UCP-2含量持续升高。这些数据支持这样的观点，即RHM中线粒体的恢复在CABG后早期被延迟，并且可能导致在儿茶酚胺激发期间氧消耗和收缩储备受损。
BackgroundWe have previously shown that mitochondrial uncoupling protein-2 (UCP-2) is increased in a swine model of hibernating myocardium (HM). Although UCP-2 reduces oxidant stress, it can promote inefficiency of the electron transport chain. In this study, we tested whether UCP-2 remains increased in revascularized HM (RHM) after coronary artery bypass grafting (CABG).MethodsSeven swine underwent thoracotomy with placement of a constrictor on the left anterior descending artery (LAD). Twelve weeks later, a left internal mammary artery graft was placed on the distal LAD. Four weeks post-CABG, computed tomography angiography documented patent grafts and function. At the terminal study, blood flow to the LAD and remote territories were assessed during high dose dobutamine and mitochondria isolated from both regions for analysis. Comparisons were made to a group of swine with HM who underwent constrictor placement without bypass grafting (n= 4).ResultsDuring dobutamine infusion, RHM demonstrated lower blood flows (2.44 ± 0.23versus3.43 ± 0.30 mL/min/g;P< 0.05) and reduced wall thickening (33 ± 9%versus52 ± 13%;P< 0.05) compared with remote regions. RHM had lower respiratory control indices (3.7 ± 0.3versus4.3 ± 0.4;P< 0.05) with persistently increased UCP-2 content.ConclusionsDespite patent grafts, RHM demonstrates a submaximal response to dobutamine infusion and increased mitochondrial UCP-2 expression. These data support the notion that recovery of the mitochondria in RHM is delayed early post-CABG and may contribute to impaired oxygen consumption and contractile reserve during catecholamine challenges.