Effects of Aspirin, Dipyridamole, and Cod Liver Oil on Accelerated Myointimal Proliferation in Canine Veno-Arterial Allografts

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Abstract
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 docasahexanoic 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 .mu.m 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 nonplatelet-mediated mechanisms. Nevertheless, this preparation is attractive as a reproducible model of accelerated (immunologically mediated) experimental arteriosclerosis.