Platelet survival and serotonin content after placement of arterial prostheses in dogs: effects of neointimal coverage and high- and low-dose aspirin.
Because prosthetic neointima produces much less prostacyclin (PGI2) than arterial intima and may be more susceptible to cyclooxygenase inhibition, aspirin treatment might enhance surface thrombogenesis. To test this hypothesis, aortic prostheses were placed in eight dogs and measurements of platelet survival and platelet serotonin (5HT) were made under conditions of no treatment and treatment with low-dose (2mg/kg) and high-dose (30 mg/kg) aspirin. These doses equally suppressed platelet function. Measurements were performed preoperatively, 6 to 8 weeks postoperatively (when little neointima was present), and 28 to 32 weeks postoperatively (neointima fully developed). Platelet survival and 5HT levels were markedly reduced 6 to 8 weeks postoperatively and returned to normal at 28 to 32 weeks after implantation. At all times, low-dose aspirin improved platelet survival and this effect was most apparent 6 to 8 weeks postoperatively. Treatment with either aspirin dose decreased platelet 5HT levels at the 28 to 32 week postoperative period but not at other times. At recovery of prostheses, 90% of the luminal surface was covered with endothelialized neointima. Neointimal production of PGI2 was one half to one third that of aortic production. Despite this, low- and high-dose aspirin equally suppressed PGI2 production from both neointima and aorta. Furthermore, aspirin did not increase labeled platelet uptake on neointima. We conclude that (1) aspirin treatment does not render prosthetic neointima thrombogenic and (2) aspirin alters platelet survival and 5HT levels by mechanisms other than inhibition of platelet and neointima cyclooxygenase.
Clagett
G P
GP
Department of Surgery, University of Texas Health Science Center, Dallas 75235-9031.
Hufnagel
H
H
Watkins
M T
MT
Sharefkin
J B
JB
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage* / Q000627:therapeutic use; D001792:Blood Platelets / Q000502:physiology*; D001807:Blood Vessel Prosthesis; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis; D006085:Graft Survival; D012701:Serotonin / Q000097:blood*
D012701:Serotonin; D011464:Epoprostenol; D001241:Aspirin