Translational model of vein graft failure following coronary artery bypass graft in atherosclerotic microswine.

Abstract

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.