A multiphased analysis in an animal model of the effects of non-anticoagulant heparin fragments and endothelial cell growth factor (ECGF) on myointimal hyperplasia (MIH) is planned to: a) develop a model of MIH using vein to artery transplant that simulates the lesion occurring in clinical practice; b) examine the ability of the non-anticoagulant heparin fragments to inhibit MIH; c) study the pharmacokinetics of ECGF in a small animal model and then; d) examine the ability of ECGF to accelerate endothelial regeneration and act synergistically with heparin in retarding MIH. Heparin fragments have been demonstrated to cause inhibition of smooth muscle cell hyperplasia, thought to be the primary mechanism of MIH. ECGF causes acceleration of endothelial cell growth in vitro. Endothelial injury an important component in the development of MIH, should be ameliorated by use of ECGF and accelerate re-endothelialization. A return of endothelium to a quiescent state should retard or prevent the progression of MIH.
