It has been suggested that inhibition of platelet cyclooxygenase by chronic low dose aspirin may spare vascular prostacyclin production. Conventional doses of aspirin (>5 mglkg) have been shown to inhibit the generation of both thromboxane A2and 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 mglkg. After 14 days of 0, 1, or 2 mglkg aspirin, intact veins and arteries were surgically removed and perfused, and luminal prostacyclin (6-keto-PGF1α,) generation was assessed. Levels of 6-keto-PGF1α in venous perfusates were reduced by 89% and 86% (p>0.05) after 1 and 2 mglkg, respectively. Arterial 6-keto-PGF1α levels were unchanged by 1 mg/kg aspirin, but after 2 mglkg were reduced by 66% (p>0.05). Preferential inhibition of platelet over arterial cyclooxygenase is thus achievable, but only over a narrow dose range.
Arteriosclerosis – Wolters Kluwer Health
Published: Nov 1, 1987