Pharmacologic modulation of intimal hyperplasia in canine vein interposition grafts. 1993

M K Hirko, and J R McShannic, and S P Schmidt, and W V Sharp, and M M Evancho, and R L Sims, and J D Siebert
Department of Surgery, Akron City Hospital, OH 44309.

OBJECTIVE 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

UI MeSH Term Description Entries
D006965 Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells. Hyperplasias
D007601 Jugular Veins Veins in the neck which drain the brain, face, and neck into the brachiocephalic or subclavian veins. Jugular Vein,Vein, Jugular,Veins, Jugular
D008297 Male Males
D001807 Blood Vessel Prosthesis Device constructed of either synthetic or biological material that is used for the repair of injured or diseased blood vessels. Vascular Prosthesis,Blood Vessel Prostheses,Tissue-Engineered Vascular Graft,Graft, Tissue-Engineered Vascular,Grafts, Tissue-Engineered Vascular,Prostheses, Blood Vessel,Prostheses, Vascular,Prosthesis, Blood Vessel,Prosthesis, Vascular,Tissue Engineered Vascular Graft,Tissue-Engineered Vascular Grafts,Vascular Graft, Tissue-Engineered,Vascular Grafts, Tissue-Engineered,Vascular Prostheses,Vessel Prostheses, Blood,Vessel Prosthesis, Blood
D002339 Carotid Arteries Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. Arteries, Carotid,Artery, Carotid,Carotid Artery
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005260 Female Females
D005263 Femoral Artery The main artery of the thigh, a continuation of the external iliac artery. Common Femoral Artery,Arteries, Common Femoral,Arteries, Femoral,Artery, Common Femoral,Artery, Femoral,Common Femoral Arteries,Femoral Arteries,Femoral Arteries, Common,Femoral Artery, Common
D006083 Graft Occlusion, Vascular Obstruction of flow in biological or prosthetic vascular grafts. Graft Restenosis, Vascular,Vascular Graft Occlusion,Vascular Graft Restenosis,Graft Restenoses, Vascular,Occlusion, Vascular Graft,Restenosis, Vascular Graft
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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