Intimal hyperplasia in autogenous vein grafts used for arterial bypass: a canine model

Late vein graft occlusion following myocardial revascularisation is usually the result of progressive intimal hyperplasia which ultimately leads to vein graft thrombosis. Considerable attention has recently been directed towards the development of optimal platelet-inhibiting drug regimens designed to prevent intimal hyperplasia in autogenous vein grafts. This report describes an animal model that reliably reproduces short-term intimal hyperplasia in autogenous vein grafts, thus facilitating the study of platelet-inhibiting drug regimens for the prevention of intimal hyperplasia. 28 segments of undistended jugular vein were implanted end-to-end between bilaterally divided femoral arteries in 14 mongrel dogs. Seven control animals (CON) received a non-lipid diet one week before and for 6 weeks following vein implantation. A further seven animals received a 2% cholesterol diet throughout the study. Serum cholesterol was measured at 4.06 ± 0.6 mmol·litre-1 in the CON and did not change significantly throughout the study. Serum cholesterol rose from 3.9 ± 0.4 to 8.5 ± 0.8 mmol·litre-1 in the lipid-supplemented animals (p<0.001). Vein grafts were harvested at 6 weeks and fixed in formaldehyde. Precise measurements of intimal thickness in microns were measured from multiple vein graft cross-sections with a Zeiss computerised interactive image analysing system. A mean of 102 ± 15 measurements were made from each vein graft cross-section. Intimal thickness of autogenous vein grafts prior to implantation were similar in both groups and measured 4.15 ± 0.4 μm. Intimal thickness increased in CON animals to 23.3 ± 3 μm. By contrast, intimal thickness was more marked in those animals receiving a lipid-supplemented diet and increased to 84 ± 14 μm (p<0.001). These data indicate that a 2% cholesterol diet results in a markedly accelerated rate of intimal hyperplasia in autogenous vein grafts used for arterial bypass and suggests that this animal model may be used in future to facilitate the study of platelet-inhibiting drug regimens, designed to prevent intimal hyperplasia in autogenous vein grafts used for arterial bypass.