Differential suppression of thromboxane biosynthesis by indobufen and aspirin in patients with unstable angina
Differential suppression of thromboxane biosynthesis by indobufen and aspirin in patients with unstable angina
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DOI：
10.1161/01.cir.96.4.1109
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发表时间：
1997-08-19
期刊：
影响因子：
37.8
通讯作者：
Maseri, A
中科院分区：
文献类型：
--
作者：
Cipollone, F;Patrignani, P;Maseri, A
背景：我们以前曾报道过阿司匹林不能抑制不稳定型心绞痛急性期血小板活化亚组中血栓素（TX）生物合成的增强。最近发现的第二种前列腺素H合酶（PGHS-2），可诱导炎症或促有丝分裂刺激，提示我们重新检查TXA（2）生物合成在不稳定型心绞痛中的作用，两种环氧合酶抑制剂对PGHS-2的影响不同，尽管对血小板PGHS-1的影响相似。（15名男性和5名女性，年龄59 +/- 10岁）患有不稳定型心绞痛的患者接受阿司匹林（320 mg/d）或吲哚布芬（200 mg BID）的短期治疗，并收集6至18个连续尿样。提取尿中11-脱氢-TXB 2，并通过先前验证的放射免疫测定法进行测量，以反映体内TXA（2）的生物合成。阿司匹林组的代谢物排泄平均为102 pg/mg肌酐（中位数; n=76），吲哚布芬组为55 pg/mg肌酐（中位数; n=99）（P <0.05）。
Background We have previously reported aspirin failure in suppressing enhanced thromboxane (TX) biosynthesis in a subset of episodes of platelet activation during the acute phase of unstable angina. The recent discovery of a second prostaglandin H synthase (PGHS-2), inducible in response to inflammatory or mitogenic stimuli, prompted us to reexamine TXA(2) biosynthesis in unstable angina as modified by two cyclooxygenase inhibitors differentially affecting PGHS-2 despite a comparable impact on platelet PGHS-1.Methods and Results We randomized 20 patients (15 men and 5 women aged 59 +/- 10 years) with unstable angina to short-term treatment with aspirin (320 mg/d) or indobufen (200 mg BID) and collected 6 to 18 consecutive urine samples. Urinary 11-dehydro-TXB2 was extracted and measured by a previously validated radioimmunoassay as a reflection of in vivo TXA(2) biosynthesis. Metabolite excretion averaged 102 pg/mg creatinine (median value; n=76) in the aspirin group and 55 pg/mg creatinine (median value; n=99) in the indobufen group (P200 pg/mg creatinine among patients treated with aspirin versus 6 such samples (6%) among those treated with indobufen (P