BLOOD-FLOW AND KINETICS OF SMOOTH-MUSCLE CELL-PROLIFERATION IN CANINEAUTOGENOUS 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 di stal poor run-off model. The in vivo bromodeoxyuridine (BrdU, a thymid ine analogue) incorporation method was used to label proliferating SMC s in each layer of the vein graft. The BrdU labeling index (LI) was de fined 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 g raft. The development of intimal thickening of grafts was accelerated at 2 to 4 weeks after implantation. In poor run-off limbs with an abno rmal blood flow condition, as characterized by a low flow and a low sh ear stress variation, the intima of the graft thickened more progressi vely than that in control limbs with a normal blood flow. In both grou ps, the medial BrdU LIs reached a maximum 3 to 5 days after implantati on 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-o ff limbs (6.34% at 1 week and 2.97% at 2 weeks) were significantly hig her than those in control limbs (5.34 and 1.98%) for 2 weeks after imp lantation (P< 0.05). The medial SMC proliferation and the following in timal SMC proliferation of vein grafts were accelerated prior to devel opment 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 stres s variation. (C) 1994 Academic Press, Inc.