The effect of platelet inhibitory therapy on prosthetic graft maturation.
Thirty-eight dogs were randomized to the thromboxane synthetase inhibitor CGS12790 (3 mg/kg), aspirin 150 mg and dipyridamole 50 mg (ASA + DPM) or placebo (PLA), all twice daily. Two days later, animals underwent bilateral superficial femoral artery replacement with knitted Dacron. Grafts were removed at two months and subjected to macroscopic and histological examination. Thirty dogs survived to two months. Percentage thrombus free area (TFA) was increased from 15.1 +/- 2.2 with PLA to 46.6 +/- 5.2 with CGS12970 (P < 0.001) and to 32.9 +/- 5.0 with ASA + DPM (P < 0.01). At the anastomoses, only CGS12970 significantly reduced neointimal thickness, promoted pannus ingrowth and improved endothelialization. Percentage luminal occlusion at the midgraft was reduced from 48.2 +/- 5.9 with PLA to 33.9 +/- 2.7 with CGS12970 (P < 0.05). These results provide further evidence that platelet inhibitory therapy reduces thrombosis but also that the platelet is involved in anastomotic maturation. Therapy directed against thromboxane synthesis has potential that may be useful in clinical practice.
Bearn
P E
PE
Bloomsbury Vascular Unit, Middlesex Hospital, London, UK.
Moffat
C
C
Seddon
A M
AM
Bull
H
H
Marston
A
A
Fox
B
B
McCollum
C N
CN
D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D001807:Blood Vessel Prosthesis; D004176:Dipyridamole / Q000627:therapeutic use; D004285:Dogs; D004359:Drug Therapy, Combination; D005260:Female; D005263:Femoral Artery / Q000601:surgery; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D004176:Dipyridamole; C049113:3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; D013930:Thromboxane-A Synthase; D001241:Aspirin