Clagett G P, Hufnagel H, Watkins M T, Sharefkin J B
Department of Surgery, University of Texas Health Science Center, Dallas 75235-9031.
J Vasc Surg. 1987 Dec;6(6):555-62.
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.
由于人工血管新生内膜产生的前列环素(PGI2)比动脉内膜少得多,并且可能对环氧合酶抑制更敏感,阿司匹林治疗可能会增强表面血栓形成。为了验证这一假设,将主动脉假体植入八只狗体内,并在未治疗以及低剂量(2mg/kg)和高剂量(30mg/kg)阿司匹林治疗的条件下测量血小板存活率和血小板5-羟色胺(5HT)。这些剂量均能同等程度地抑制血小板功能。在术前、术后6至8周(此时新生内膜较少)以及术后28至32周(新生内膜完全形成)进行测量。术后6至8周血小板存活率和5HT水平显著降低,植入后28至32周恢复正常。在所有时间点,低剂量阿司匹林均能改善血小板存活率,且这种效果在术后6至8周最为明显。两种阿司匹林剂量治疗在术后28至32周时均降低了血小板5HT水平,但在其他时间未降低。在取出假体时,90%的管腔表面覆盖有内皮化的新生内膜。新生内膜中PGI2的产生量是主动脉产生量的二分之一至三分之一。尽管如此,低剂量和高剂量阿司匹林均能同等程度地抑制新生内膜和主动脉中PGI2的产生。此外,阿司匹林并未增加新生内膜上标记血小板的摄取。我们得出结论:(1)阿司匹林治疗不会使人工血管新生内膜具有血栓形成性;(2)阿司匹林通过抑制血小板和新生内膜环氧合酶以外的机制改变血小板存活率和5HT水平。