Neointimal formation at the sites of anastomosis of the internal thoracic artery grafts after coronary artery bypass grafting in human subjects: An immunohistochemical analysis

Objectives: The aim of this study was to evaluate the cellular composition and cell proliferative activity of neointimal tissue in human internal thoracic artery grafts and to characterize the differentiation stale of neointimal smooth muscle cells at early stages after coronary artery bypass grafting. Methods: The anastomotic sites and body segments of 7 patent grafts were obtained at autopsy from 7 patients who died within 92 days after operation. Serial sections were examined by immunohistochemical techniques to identify macrophages, endothelial cells, smooth muscle cell phenotype, and proliferating cells. For the identification of the cell types that show cell proliferative activity, immunodouble staining was also performed. Results: In all body segments the luminal surface was completely covered by endothelial cells, and no areas showed thrombus formation or neointimal proliferation after grafting. In contrast, in the anastomotic segments endothelial denudation and focal disruption of the internal elastic lamina with adherence of fibrin-platelet thrombus and infiltration of macrophages were observed in the earliest stage after grafting. At these sites of injury, early neointimal tissue response had occurred, and cell proliferative activity was detected in macrophages and dedifferentiated smooth muscle cells. During the evolution of neointimal thickening, redifferentiation of neointimal smooth muscle cells occurred associated with the decline in proliferative activity. Conclusions: These observations strongly support the concept that excessive neointimal proliferation, which may occur at the site of anastomosis because of extensive damage to the arterial wall, could be one of the possible causes of failure of the internal thoracic artery graft in human beings.