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Venous injury following mechanical distension and its late sequelae were studied in a canine model. Jugular vein segments distended without and with papaverine (60 mg/100 ml) were compared with nondistended vein segments after they had been placed into the arterial circulation for 1 to 12 months. Arteriography showed no significant statistical discrepancy in luminal diameter of the three vein segments. Complete reendothelialization had occurred in all vein grafts at the time of harvesting. Similar histocytologic features existed in the nondistended segments and in the portion distended with human plasma protein fraction (Plasmanate) plus papaverine (150 to 300 mm Hg). The intimal-medial hyperplasia was characterized by an increase in fibrocellular layers with an elaboration of vasa vasorum. Conversely, collagen and extracellular matrix replaced the myocyte, producing medial fibrosis in vein mechanically distended with Plasmanate alone. Papaverine prevented mechanical stimulation of smooth muscle cells to overproduce extracellular connective tissue elements. Mechanical stretching of intimal and medial myocytes induced fibrogenesis and fibroplasia. Papaverine is useful in vein preparation; it protects the endothelium and smooth muscle cells in the intima and media and prevents leukocyte infiltration and medial fibrosis.