PHARMACOLOGICAL MODULATION OF INTIMAL HYPERPLASIA IN CANINE VEIN INTERPOSITION GRAFTS

Purpose: The purpose of this study was to evaluate the efficacy of thr ee drugs (cilazapril, cyclosporine, and aspirin) in modulating the pro gression of intimal hyperplasia during short postoperative times in sh ort-segment, autogenous vein bypass grafts in a canine model. The rela tive effects of the drugs on the progression of intimal hyperplasia we re compared with the Gilman parameter, a measure used extensively as a wound heating descriptor. To our knowledge this is the first use of t he Gilman parameter in assessing vascular disease. Methods: Seventy-tw o conditioned mongrel dogs were randomly and equally divided according to a three-factor analysis of variance. The factors included (1) drug treatments (cilazapril [10 mg/kg/day], cyclosporine [4 mg/kg/day], as pirin [325 mg/day], and control [nonmedicated]), (2) implantation site s (femoral and carotid arteries), and (3) postoperative times of graft harvest (1, 3, and 6 weeks). Each dog had 2 cm segments of autogenous jugular vein interpositioned bilaterally into each of the paired caro tid and femoral arteries. Quantitative data on luminal narrowing over time from intimal hyperplasia were compared from calculated Gilman par ameters after image analysis of retrieved, histologically processed gr aft sections. Results: The observed variability in the data was attrib uted to drug treatments and time. At 1 week after operation the mean G ilman parameters did not differ significantly among the treatment grou ps in either midgraft or distal graft segments. At 3 weeks the mean Gi lman parameters of midgraft and distal graft sections of cyclosporine- treated dogs differed significantly (p < 0.05) from those of the contr ol group and the cilazapril and aspirin-treated groups, which did not differ from each other. At 6 weeks after operation, mean Gilman parame ters from aspirin- and cyclosporine-treated dogs differed statisticall y from control and cilazapril-medicated dogs and from each other (p < 0.001). Conclusions: These data support the efficacy of aspirin and cy closporine in reducing intimal hyperplasia in short-segment arterializ ed vein grafts during short postoperative periods. Additional studies are required to ascertain whether the beneficial effects of aspirin an d cyclosporine persist long-term.