Blood flow and kinetics of smooth muscle cell proliferation in canine autogenous vein grafts: in vivo BrdU incorporation.

The effects of blood flow on the kinetics of smooth muscle cell (SMC) proliferation were examined in canine autogenous vein grafts with a distal poor run-off model. The in vivo bromodeoxyuridine (BrdU, a thymidine analogue) incorporation method was used to label proliferating SMCs in each layer of the vein graft. The BrdU labeling index (LI) was defined as a percentage of labeled cells compared to the total number of SMCs, and BrdU LIs were measured in the media and the intima of the graft. The development of intimal thickening of grafts was accelerated at 2 to 4 weeks after implantation. In poor run-off limbs with an abnormal blood flow condition, as characterized by a low flow and a low shear stress variation, the intima of the graft thickened more progressively than that in control limbs with a normal blood flow. In both groups, the medial BrdU LIs reached a maximum 3 to 5 days after implantation and decreased thereafter. The peak of the intimal BrdU LIs occurred at 1 week in both groups. The intimal LIs of the grafts in poor run-off limbs (6.34% at 1 week and 2.97% at 2 weeks) were significantly higher than those in control limbs (5.34 and 1.98%) for 2 weeks after implantation (P < 0.05). The medial SMC proliferation and the following intimal SMC proliferation of vein grafts were accelerated prior to development of the intimal thickening. SMC proliferation in the intima was prominent in a poor run-off limb with a low flow and a low shear stress variation.