The integrity of experimental vein graft endothelium—implications on the etiology of early graft failure

Abstract

the vascular endothelium serves as a functional barrier between the circulating blood and the vessel wall. It is an essential element for the maintenance of vascular homeostasis and is implicated in the pathogenesis of vascular disease. Reversed vein bypass grafting is considered to be a devastating procedure for the endothelial cell layer of the graft during the first 7 days. At this time, smooth muscle cell proliferation, the forerunner of intimal hyperplasia, begins. Loss of endothelial cell integrity is cited as an important factor in this smooth muscle cell response. The integrity of the vein graft endothelial lining after grafting was examined in this study. reversed vein bypass grafting of the common carotid artery using external jugular vein was performed in 24 New Zealand white rabbits. All grafts were pressure fixed (80 mmHg) in situ, at 0 and 10 min, 6 h and 1, 3, 5, 7 and 14 days postoperatively. The endothelial cell layer was examined by light microscopy (LM), scanning (SEM) and transmission electron microscopy (TEM) and immunohistochemistry (Factor VIII) using standard histological procedures. the endothelium was observed by SEM and confirmed by both LM, Factor VIII and TEM in all specimens. It covered almost the entire surface examined. At 0 and 10 min, endothelial cells were present and displayed minimal evidence of injury. At 6 h and 1 day, numerous red cells, polymorphonucleocytes (PMNs), platelets and fibrin were adherent to the luminal surface. Blood cells were also seen beneath the endothelium. At day 3, the adherent fibrin and cellular elements were reduced with most of the endothelial lining intact. Within 10 min, TEM demonstrated that these cells were stretched, very thin with few microvesicles and a blurred cytoplasm, which would indicate viability but a degree of cellular injury. By day 1, the endothelial cells were lifted from their underlying structures by subendothelial oedema and an infiltrate predominantly of PMNs. By day 5, the blood cells and fibrin which were adherent to the endothelium had been dispersed and the subendothelial infiltrate was to a large extent replaced by disintegrated PMNs. On days 7 and 14, a viable confluent endothelial cell layer was present and a degree of intimal hyperplasia was noted. The endothelial cells appeared to have enlarged nucleoli and cytoplasms filled with a considerable quantity of rough endoplasmic reticulum. the endothelium of reversed vein grafts is preserved at the time of implantation and at all time intervals studied in this model. These findings do not support the assumption that endothelial denudation is a prerequisite for intimal hyperplasia. Endothelial cell dysfunction and morphological changes are maximal within the first 3 days after grafting but appear to recover by the 5th postoperative day. The gross preservation of the endothelial cell layer implies that therapeutic approaches, to mitigate endothelial cell injury and its consequences, should be focused on the preoperative period and the first 5 days following implantation.