Objective

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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动脉粥样硬化微型猪冠状动脉旁路移植术后静脉移植失败的平移模型

客观的

静脉移植失败是冠状动脉搭桥手术后的主要并发症。没有转化模型来理解静脉移植失败的分子机制。我们建立了一个临床相关的旁路移植模型，以研究静脉移植失败的潜在病理生理机制，并确定新疗法的分子靶点。

方法

6 只喂食高胆固醇饮食的雌性尤卡坦微型猪接受了非体外循环，使用浅表上腹静脉移植物，将其与乳内动脉和左前降支远端吻合。在旁路手术后 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的通畅性，然后实施安乐死。收集冠状组织用于组织形态学研究。

结果

动脉粥样硬化的微型猪对任何心脏干预的突然心室颤动非常敏感。由于心室颤动，六只动物中有两只在手术期间死亡。麻醉剂的选择和剂量的滴定以及仔细使用正性肌力药物是猪心脏麻醉成功的关键。硫酸镁可避免胺碘酮的降压作用和心律失常的发生。静脉移植对照组织显示完整的内皮，内层组织良好。移植血管显示完全闭塞并被纤维组织覆盖。移植物中CD31的表达是不规则的，因为这些层由于纤维化而没有明确定义。

结论

该模型代表了临床静脉移植失败，并提供了一个新的平台来研究静脉移植疾病的潜在分子机制，并研究防止其进展的新治疗方法。