Department of Translational Research, Western University of Health Sciences, Pomona, CA, 91766, USA.
Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, 68178, USA.
Gen Thorac Cardiovasc Surg. 2022 May;70(5):445-454. doi: 10.1007/s11748-021-01725-y. Epub 2021 Oct 26.
Vein graft failure is a major complication following coronary artery bypass graft surgery. There is no translational model to understand the molecular mechanisms underlying vein-graft failure. We established a clinically relevant bypass graft model to investigate the underlying pathophysiological mechanisms of vein-graft failure and identify molecular targets for novel therapies.
Six female Yucatan microswine fed with high cholesterol diet underwent off-pump bypass, using superficial epigastric vein graft, which was anastomosed to an internal mammary artery and distal left anterior descending artery. Vein-graft patency was examined 10-months after bypass surgery by echocardiography, coronary angiography, and optical coherence tomography followed by euthanasia. Coronary tissues were collected for histomorphometry studies.
Atherosclerotic microswine were highly susceptible to sudden ventricular fibrillation with any cardiac intervention. Two out of six animals died during surgery due to ventricular fibrillation. Selection of the anesthetics and titration of their doses with careful use of inotropic drugs were the key to successful swine cardiac anesthesia. The hypotensive effects of amiodarone and the incidence of arrhythmia were avoided by the administration of magnesium sulfate. The vein-graft control tissue displayed intact endothelium with well-organized medial layer. The grafted vessels revealed complete occlusion and were covered with fibrous tissues. Expression of CD31 in the graft was irregular as the layers were not clearly defined due to fibrosis.
This model represents the clinical vein-graft failure and offers a novel platform to investigate the underlying molecular mechanisms of vein-graft disease and investigate novel therapeutic approaches to prevent its progression.
静脉移植物失败是冠状动脉旁路移植手术后的主要并发症。目前尚无转化模型来了解静脉移植物失败的分子机制。我们建立了一个具有临床相关性的旁路移植模型，以研究静脉移植物失败的潜在病理生理机制，并确定新疗法的分子靶点。
六只喂食高胆固醇饮食的雌性尤卡坦微型猪进行非体外循环旁路手术，使用腹壁浅静脉移植物，将其吻合到内乳动脉和左前降支的远端。旁路手术后 10 个月，通过超声心动图、冠状动脉造影和光学相干断层扫描检查静脉移植物通畅情况，然后安乐死。收集冠状动脉组织进行组织形态学研究。
动脉粥样硬化微型猪在任何心脏干预时都极易发生突发性心室颤动。六只动物中有两只在手术过程中因心室颤动而死亡。选择麻醉剂并通过仔细使用正性肌力药物滴定其剂量是成功进行猪心脏麻醉的关键。胺碘酮的低血压作用和心律失常的发生率通过给予硫酸镁得以避免。静脉移植物对照组织显示完整的内皮，中层排列整齐。移植血管完全闭塞，覆盖着纤维组织。由于纤维化，移植物的 CD31 表达不规则，各层不清晰。
该模型代表了临床静脉移植物失败，并为研究静脉移植物疾病的潜在分子机制以及研究预防其进展的新治疗方法提供了一个新的平台。
