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 thor acic artery grafts and to characterize the differentiation stale of neointi mal smooth muscle cells at early stages after coronary artery bypass grafti ng. Methods: The anastomotic sites and body segments of 7 patent grafts were ob tained 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 prolifer ating cells. For the identification of the cell types that show cell prolif erative 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 pr oliferation after grafting. In contrast, in the anastomotic segments endoth elial denudation and focal disruption of the internal elastic lamina with a dherence of fibrin-platelet thrombus and infiltration of macrophages were o bserved in the earliest stage after grafting. At these sites of injury, ear ly neointimal tissue response had occurred, and cell proliferative activity was detected in macrophages and dedifferentiated smooth muscle cells. Duri ng the evolution of neointimal thickening, redifferentiation of neointimal smooth muscle cells occurred associated with the decline in proliferative a ctivity. Conclusions: These observations strongly support the concept that excessive neointimal proliferation, which may occur at the site of anastomosis becau se of extensive damage to the arterial wall, could be one of the possible c auses of failure of the internal thoracic artery graft in human beings.