The effect of low molecular weight heparin on intimal hyperplasia in vein grafts

Abstract

Intimal hyperplasia due to smooth muscle cell proliferation is a well recognised cause of vascular graft failure. In experimental studies heparin and its low molecular weight derivatives can inhibit this proliferative response. This study examines the effect of subcutaneous low molecular weight heparin (LMWH) therapy on intimal hyperplasia in a model of arterial vein grafting. Twenty-four New Zealand White rabbits underwent interposition vein grafting of the carotid artery. Animals were randomly assigned to a control or treated group. Treated animals received 60 anti Xa units/kg of subcutaneous LMWH daily for 1 month. Animals were then sacrificed, graft patency assessed and the vessels then harvested for analysis of intimal hyperplasia. Intimal hyperplasia in carotid arteries and vein grafts was measured using a computerised image analysis system and was expressed as an intimal:medial area ratio. A statistically significant reduction in the degree of intimal hyperplasia seen in the arterial component of the distal anastomoses of carotid vein grafts was achieved using subcutaneous LMWH [Control 0.44 (0.37-0.55): LMWH 0.27 (0-0.37) p < 0.05]. There was no difference in the degree of intimal hyperplasia seen in the vein grafts themselves. [Control 0.21 (0-0.54): LMWH 0.23 (0-0.72)]. This study suggests that subcutaneous LMWH can inhibit the development of intimal hyperplasia in arteries undergoing vascular grafting but does not influence intimal hyperplasia within vein grafts. This has important implications for the further evaluation of antithrombotic agents following vascular surgery.