Effects of aspirin, dipyridamole, and cod liver oil on accelerated myointimal proliferation in canine veno-arterial allografts.
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.
DeCampli
W M
WM
Department of Cardiovascular Surgery, Stanford University School of Medicine, California 94305-5247.
Kosek
J C
JC
Mitchell
R S
RS
Handen
C E
CE
Miller
D C
DC
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003060:Cod Liver Oil / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology*; D004285:Dogs; D004547:Elastic Tissue / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005268:Femoral Vein / Q000473:pathology / Q000637:transplantation; D005395:Fish Oils / Q000494:pharmacology*; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000517:prevention & control; D006470:Hemorrhage / Q000473:pathology; D008297:Male; D013927:Thrombosis / Q000473:pathology; D014654:Vascular Patency / Q000187:drug effects*
D002791:Cholesterol, Dietary; D005395:Fish Oils; D004176:Dipyridamole; D003060:Cod Liver Oil; D001241:Aspirin