OPTIMAL DOSE AND DURATION OF HEPARIN FOR INHIBITION OF INTIMAL HYPERPLASIA

Background. A Dacron patch graft was placed in the common carotid arte ry of sheep to assess the effect of three different doses of unfractio nated heparin. administered for periods of one to four weeks. Material s and methods. Animals were divided into a control group (n = 6) in wh ich animals received a patch graft but no heparin and three main treat ment groups on the basis of the dose of heparin received. Group 1 anim als (n = 24) received 140 units per kg daily in two divided doses. Gro up 2 (n = 24) received 280 units per kg daily and Group 3 (n = 24) rec eived 420 units per kg daily. Each treatment group was further divided into four subgroups on the basis of the duration of treatment. Groups 1(i), 2(i), 3(i) had treatment for one week. Groups 1(ii), 2(ii), 3(i i) had treatment for two weeks. Groups 1(iii), 2(iii), 3(iii) had trea tment for three weeks. Groups 1(iv), 2(iv), 3(iv) had treatment for fo ur weeks. There were six animals in each subgroup giving a total of 72 treated sheep. Animals were sacrificed at four weeks and an intimal m easurement in mu m was obtained under light microscopy from a transver se sectioned segment of artery containing the patch graft using an eye piece graticule. Results. There were no haemorrhagic complications. Co ntrol animals had a mean intimal thickness of 176 pm. All treatment gr oups had significantly less IH - Group 1 131.9 (p < 0.01), Group 2 138 .5 (p < 0.05), Group 3 117.8 (p < 0.01). There were no significant dif ferences between the treatment groups. There was significantly less IH in animals treated for four weeks (106.3) compared to one week (140.2 , p < 0.05). Conclusions. This study indicates that inhibition of IH c an be achieved by heparin with optimal effect from a four week treatme nt period.