Pharmacologic modulation of intimal hyperplasia in canine vein interposition grafts

The purpose of this study was to evaluate the efficacy of three drugs (cilazapril, cyclosporine, and aspirin) in modulating the progression of intimal hyperplasia during short postoperative times in short-segment, autogenous vein bypass grafts in a canine model. The relative effects of the drugs on the progression of intimal hyperplasia were compared with the Gilman parameter, a measure used extensively as a wound healing descriptor. To our knowledge this is the first use of the Gilman parameter in assessing vascular disease.

Seventy-two 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], aspirin [325 mg/day], and control [nonmedicated]), (2) implantation sites (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 carotid and femoral arteries. Quantitative data on luminal narrowing over time from intimal hyperplasia were compared from calculated Gilman parameters after image analysis of retrieved, histologically processed graft sections.

The observed variability in the data was attributed to drug treatments and time. At 1 week after operation the mean Gilman parameters did not differ significantly among the treatment groups in either midgraft or distal graft segments. At 3 weeks the mean Gilman parameters of midgraft and distal graft sections of cyclosporine-treated dogs differed significantly (p < 0.05) from those of the control group and the cilazapril and aspirin-treated groups, which did not differ from each other. At 6 weeks after operation, mean Gilman parameters from aspirin- and cyclosporine-treated dogs differed statistically from control and cilazapril-medicated dogs and from each other (p < 0.001).

These data support the efficacy of aspirin and cyclosporine in reducing intimal hyperplasia in short-segment arterialized vein grafts during short postoperative periods. Additional studies are required to ascertain whether the beneficial effects of aspirin and cyclosporine persist long-term.