Effect of heparin on adaptation of vein grafts to arterial circulation

We studied the effect of heparin on wall thickening in balloon-injured carotid arteries and vein grafts in rabbits. Heparin (0.3 mg/kg of body weight/hour) reduced intimal cross-sectional area in balloon-injured carotid arteries at 2 weeks (0.20 +/- 0.05 mm2 vs. 0.05 +/- 0.02 mm2, p = 0.02). Autoradiography after a single pulse of tritiated thymidine revealed no labeling in the few intimal cells present in heparin-treated animals, whereas control smooth muscle cells (SMC) had a 10% labeling index. Heparin did not affect medial proliferation, suggesting that the decrease in intimal thickening was largely due to inhibition of SMC migration into the intima. Heparin caused a slight reduction in intimal cross-sectional area at 2 weeks in vein grafts (0.17 +/- 0.03 mm2 vs. 0.09 +/- 0.02 mm2, p = 0.03) but no significant reduction in wall thickness at any other time and no reduction in SMC proliferation rate (thymidine labeling index). DNA content per surface area or dry weight was the same in control and heparin-treated vein grafts at 4 weeks, implying that SMC content and the amount of matrix made by individual SMC was not affected. These data suggest that either SMC in veins are less susceptible to heparin than SMC in arteries, or the mechanism of thickening is substantially different. Heparin may not block all forms of SMC proliferation and may only be a weak inhibitor in processes that primarily are in response to changes in pressure.