Jakubowski J A, Bush H L, Vaillancourt R, Deykin D
Boston Veterans Administration Medical Center, Massachusetts 02130.
Arteriosclerosis. 1987 Nov-Dec;7(6):599-604. doi: 10.1161/01.atv.7.6.599.
It has been suggested that inhibition of platelet cyclooxygenase by chronic low dose aspirin may spare vascular prostacyclin production. Conventional doses of aspirin (greater than 5 mg/kg) have been shown to inhibit the generation of both thromboxane A2 and prostacyclin. Low dose aspirin inhibits prostacyclin production by excised human venous tissue, thus questioning the selectivity of such regimens. However, many clinical and surgical conditions requiring platelet inhibition involve the arterial system. We have studied the effects of various aspirin regimens on platelet, venous, and arterial cyclooxygenase activity in a nonhuman primate (Macaca fascicularis). We determined the lowest chronic dose of oral aspirin required to effectively inhibit platelet cyclooxygenase and aggregation to be 1 mg/kg. After 14 days of 0, 1, or 2 mg/kg aspirin, intact veins and arteries were surgically removed and perfused, and luminal prostacyclin (6-keto-PGF1 alpha) generation was assessed. Levels of 6-keto-PGF1 alpha in venous perfusates were reduced by 89% and 86% (p less than 0.05) after 1 and 2 mg/kg, respectively. Arterial 6-keto-PGF1 alpha levels were unchanged by 1 mg/kg aspirin, but after 2 mg/kg were reduced by 66% (p less than 0.05). Preferential inhibition of platelet over arterial cyclooxygenase is thus achievable, but only over a narrow dose range.
有人提出，长期低剂量阿司匹林抑制血小板环氧化酶可能会使血管前列环素的生成不受影响。传统剂量的阿司匹林（大于5mg/kg）已被证明会抑制血栓素A2和前列环素的生成。低剂量阿司匹林会抑制离体人静脉组织中前列环素的生成，因此对这种给药方案的选择性提出了质疑。然而，许多需要抑制血小板的临床和手术情况都涉及动脉系统。我们研究了不同阿司匹林给药方案对非人灵长类动物（食蟹猴）血小板、静脉和动脉环氧化酶活性的影响。我们确定有效抑制血小板环氧化酶和聚集所需的最低口服阿司匹林慢性剂量为1mg/kg。在给予0、1或2mg/kg阿司匹林14天后，完整的静脉和动脉被手术切除并进行灌注，并评估管腔内前列环素（6-酮-前列腺素F1α）的生成。在给予1mg/kg和2mg/kg阿司匹林后，静脉灌注液中6-酮-前列腺素F1α的水平分别降低了89%和86%（p<0.05）。1mg/kg阿司匹林对动脉6-酮-前列腺素F1α水平没有影响，但在给予2mg/kg后降低了66%（p<0.05）。因此，虽然可以实现对血小板环氧化酶的优先抑制而非动脉环氧化酶，但仅在很窄的剂量范围内。
