OBJECTIVES:To investigate the effect of low molecular weight heparin (LMWH) on neointimal proliferation in cultured human saphenous vein, a model of human vein graft intimal hyperplasia.DESIGN:Dose ranging LMWH concentration study.SETTING:Culture Laboratory, Department of Surgery.MATERIALS:Fifteen segments of human long saphenous vein were incubated at 37 degrees C for 14 days in culture medium with 30% foetal calf serum. LMWH was added to one of the paired segments at 1, 10 and 100 micrograms/ml (five veins each dose). 5-bromo-2-deoxyuridine (Brd-U) was used to label proliferating cells.CHIEF OUTCOME MEASURES:Neointimal thickness (micron and proliferation index (% labelled neointimal cells).MAIN RESULTS:Neointimal thickness and proliferation index were both significantly reduced by LMWH at 100 micrograms/ml [control vs. LMWH, reduction in thickness 21 microns vs. 7 microns (median difference 12 microns, 95% conf. int. 6-18), reduction in proliferation index 33% to 6% (median difference 19%, 95% C.I. 4-32)].CONCLUSIONS:High dose LMWH reduces neointimal proliferation in cultured human saphenous vein. The practical clinical application of these results may require the use of non anticoagulant heparin-like molecules and/or local drug delivery systems.

The precise histopathological nature of vein graft stenoses is unclear. Some authors have suggested that these lesions are due to intimal hyperplasia and others have claimed that they are fibrous strictures. The aim of this study was to determine the histological nature of infrainguinal vein graft stenoses by examining sections of vein grafts that had developed stenoses and had been surgically revised. This was performed using a combined anti-smooth muscle actin/Millers elastin stain. The results show that vein graft stenoses are due to intimal hyperplasia whereby smooth muscle cells proliferate and cause thickening of the intimal layer.

Although knowledge of the biological processes involved in the development of intimal hyperplasia has increased markedly in recent years, the precise aetiology of infrainguinal vein graft stenosis remains undetermined. Current therapy is therefore directed at treatment of the established lesion rather than its prevention. There seems little doubt, however, that recent advances in understanding of the vascular biology of normal and pathological saphenous vein will eventually lead to specific targeted therapy that will allow the prevention of vein graft stenosis.

Endothelial cell seeding has been proposed as a method of improving patency rates in small-calibre prosthetic vascular grafts. In vivo, endothelial cells normally produce prostacyclin (PGI2), a potent antiplatelet agent. The aim of this study was to determine whether seeded grafts show significant PGI2 production after in vivo implantation. Grafts were seeded with either autologous canine venous endothelial cells or autologous microvascular endothelial cells. After 12 weeks, PGI2 production was assessed under basal and stimulated conditions. Seeded grafts were compared with non-seeded controls and the corresponding aorta. The overall patency rate in seeded grafts was 80 per cent compared with 10 per cent in non-seeded grafts (P < 0.01). Grafts seeded with cells from either source produced significantly more PGI2 than unseeded grafts in both basal and stimulated states (P < .05). The aorta produced significantly more PGI2 than seeded grafts under both conditions (P < 0.01). Endothelial cell seeding produces a functional graft aid leads to an improved patency rate.

Endothelial cell seeding has been proposed as a method to improve the patency rates in small calibre prosthetic vascular grafts. The seeding methods used at present leave much of the graft luminal surface devoid of endothelial cells and thus still significantly thrombogenic. We have developed a method to preform confluent endothelial cell monolayers, on the grafts prior to implantation, and this study investigates the effect of these monolayers on the early thrombogenicity and patency of polytetrafluoroethylene (PTFE) grafts. Small diameter PTFE grafts were seeded with canine endothelial cells obtained from the external jugular vein. Each of five dogs then received a graft seeded with its own cells and a contralateral, non-seeded control graft. At 1 and 10 weeks after graft implantation graft thrombogenicity was assessed by the use of Indium labelled platelets. The thrombogenicity index (TI) of each graft was determined from counts of gamma activity recorded over a period of 7 days. Grafts were subsequently removed at 12 weeks. At 1 week the mean TI for the seeded grafts was 0.123 (SD 0.019) and that for the controls 0.183 (SD 0.017) (p = 0.005). At 10 weeks only the seeded grafts could be assessed because all of the control grafts had occluded. At this point in time the seeded grafts had a mean TI of 0.159 (SD 0.011) (p = 0.047 vs. seeded at 1 week). By the time of removal at 12 weeks, all control grafts were occluded but only one of the seeded grafts had occluded (p = 0.025). In conclusion, the use of preformed, confluent endothelial cell monolayers for seeding prosthetic grafts significantly reduces the early graft thrombogenicity and improves graft patency. It does not, however, completely halt the increase in thrombogenicity which occurs during the early post-implantation period.