Effects of aspirin, dipyridamole, and cod liver oil on accelerated myointimal proliferation in canine veno-arterial allografts

• Published in: Annals of surgery 1988-12, Vol.208 (6), p.746-754
• Main Authors: DECAMPLI, W. M, KOSEK, J. C, MITCHELL, R. S, HANDEN, C. E, MILLER, D. C
• Format: Article
• Language: English
• Subjects: Animals; Aspirin - pharmacology; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Cholesterol, Dietary - administration & dosage; Cod Liver Oil - pharmacology; Dipyridamole - pharmacology; Dogs; Elastic Tissue - pathology; Endothelium, Vascular - drug effects; Endothelium, Vascular - pathology; Female; Femoral Vein - pathology; Femoral Vein - transplantation; Fish Oils - pharmacology; Graft Occlusion, Vascular - pathology; Graft Occlusion, Vascular - prevention & control; Hemorrhage - pathology; Male; Medical sciences; Pharmacology. Drug treatments; Thrombosis - pathology; Vascular Patency - drug effects
• ISSN: 0003-4932; 1528-1140
• DOI: 10.1097/00000658-198812000-00013

The effects of the administration of aspirin (ASA), dipyridamole (DPM), and cod liver oil (CLO) on graft patency rate and degree of intimal hyperplasia were investigated in a canine, hypercholesterolemic veno-arterial allograft model in an attempt to modify this immunologically mediated vascular injury. The drug regimens were ASA 1 mg/kg/day, DPM 10 mg/kg/day, combined ASA and DPM (ASA + DPM), and CLO (1.8 g/day eicosapentanoic acid [EPA] and 1.2 g/day docosahexanoic acid [DHA]), and control. The early angiographic patency rate (1-3 weeks) was 81% +/- 10% (+/- 70% confidence limits); the 90-day overall patency rate was 60% +/- 4% (87/144), with no statistically significant differences among the groups (range 46 +/- 10-71 +/- 9%). Qualitatively, there was no difference in luminal thrombus, intimal hemorrhage, or lesion eccentricity. Considering the relatively short time of graft implantation, an extensive amount of microscopic disease was observed; quantitatively, the mean intimal thickness was 515 +/- 17 microgram overall but was not statistically different between the groups. The fraction of potential lumenal area occupied by intimal thickening was 0.37 +/- 0.01 but again did not differ significantly between the groups. These doses of ASA, DPM, ASA + DPM, and CLO did not alter graft occlusion or retard the marked degree of subintimal myointimal cell hyperplasia that was generated in this hypercholesterolemic canine veno-arterial allograft preparation. Possible explanations for these negative findings include inadequate dosage or form of omega-3 fatty acids and the antiplatelet drugs administered, excessive variability in graft response due to uncharacterized immunologic histocompatibility, and the possible influence of non-platelet-mediated mechanisms. Nevertheless, this preparation is attractive as a reproducible model of accelerated (immunologically mediated) experimental arteriosclerosis.