Antiproliferative effects of low molecular weight heparin

Aim: To investigate the effect of low molecular weight heparins (LMWH) on the inhibition of intimal hyperplasia (IH) developing in prosthetic vascular patch graft implanted into sheep carotid artery. Methods: A gelatin sealed Dacron patch graft was implanted into the common carotid artery of sheep, which were then allocated to a control group (n = 10) or to one of four treatment groups (each group n = 10) receiving either a low dose (LD) or high dose (HD) of one of two LMWH (enoxaparin 1 or 2 mg/kg/day, dalteparin 100 or 200 units/kg/day) administered subcutaneously for 4 weeks. Anti-activated factor X and activated partial thromboplastin time were assayed from blood collected prior to and at 1 and 2 h after LMWH administration on days 3, 7, 14, 21 and 28. Animals were killed on day 28 after taking blood samples prior to, then at 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 h following the last injection. Grafts were collected for analysis and measurements of intimal thickness obtained under light microscopy from eight transverse sections of each grafted artery aided by computer image analysis. An IH index was calculated by dividing the area of IH (mm(2)) by the width of the graft (mm). Results: Intimal hyperplasia index measurements (mean +/- SD) were: controls 0.574 +/- 0.077, LD enoxaparin 0.471 +/- 0.056, LD dalteparin 0.404 +/- 0.025, HD enoxaparin 0.398 +/- 0.068, HD dalteparin 0.332 +/- 0.048. The reductions in IH index compared to controls were significant (P < 0.05) for both LD and HD dalteparin and for HD enoxaparin. Conclusion: Both LMWH dalteparin and enoxaparin reduced the amount of IH formation with dalteparin showing a greater effect in the present animal study. The possibility that different LMWH might exert differing antiproliferative effects requires further investigation.