van Kooten F, Ciabattoni G, Patrono C, Dippel D W, Koudstaal P J
Department of Neurology, University Hospital Rotterdam, Netherlands.
Stroke. 1997 Aug;28(8):1557-63. doi: 10.1161/01.str.28.8.1557.
Both platelet activation and lipid peroxidation are potential sources of vasoactive eicosanoids that can be produced via the cyclooxygenase pathway, ie, thromboxane (TX) A2, or by free radical-catalyzed peroxidation of arachidonic acid, ie, isoprostanes. We investigated the biosynthesis of TXA2 and F2-isoprostanes, as reflected by the urinary excretion of 11-dehydro-TXB2 and 8-epi-prostaglandin (PG) F2 alpha respectively, in 62 consecutive patients (30 men, 32 women; mean age, 67 +/- 14 years) with acute ischemic stroke.
At least two consecutive 6-hour urine samples were obtained during the first 72 hours after onset of symptoms. Urinary eicosanoids were measured by previously described radioimmunoassays.
Repeated periods of enhanced thromboxane biosynthesis were found in 52% of patients. Urinary 11-dehydro-TXB2 averaged 221 +/- 207 (mean +/- SD; n = 197; range, 13 to 967) pmol/mmol creatinine in 30 patients treated with cyclooxygenase inhibitors (mostly aspirin) at the time of study versus 392 +/- 392 (n = 186; range, 26 to 2533) in 32 untreated patients (P < .001). The corresponding values for 8-epi-PGF2 alpha excretion were 74 +/- 42 (range, 14 to 206) and 83 +/- 65 (range, 24 to 570) pmol/mmol creatinine (P > .05). The correlation between the two metabolites was moderate in both untreated patients (r = .41, P < .001) and patients with cyclooxygenase inhibitors (r = .31, P < .001). In a multiple regression analysis, increased thromboxane production was independently associated with severity of stroke on admission, atrial fibrillation, and treatment with cyclooxygenase-inhibiting drugs.
We conclude that during the first few days after an acute ischemic stroke (1) platelet activation occurs repeatedly in a cyclooxygenase-dependent fashion; (2) platelet activation is not associated with concurrent changes in isoprostane biosynthesis; (3) platelet activation is independently associated with stroke severity and atrial fibrillation; and (4) isoprostane biosynthesis is largely independent of platelet cyclooxygenase activity.
血小板活化和脂质过氧化均是血管活性类二十烷酸潜在的来源，这些类二十烷酸可通过环氧化酶途径产生，即血栓素（TX）A2，或由自由基催化的花生四烯酸过氧化反应产生，即异前列腺素。我们研究了62例急性缺血性卒中连续患者（30例男性，32例女性；平均年龄67±14岁）中TX A2和F2 -异前列腺素的生物合成情况，分别通过尿中11 -脱氢 - TXB2和8 -表 - 前列腺素（PG）F2α的排泄量来反映。
在症状发作后的前72小时内至少采集两个连续的6小时尿液样本。尿类二十烷酸通过先前描述的放射免疫分析法进行测定。
52%的患者发现有反复的血栓素生物合成增强期。在研究时，30例接受环氧化酶抑制剂（主要是阿司匹林）治疗的患者尿中11 -脱氢 - TXB2平均为221±207（均值±标准差；n = 197；范围13至967）pmol/mmol肌酐，而32例未治疗患者中为392±392（n = 186；范围26至2533）（P <.001）。8 -表 - PGF2α排泄的相应值分别为74±42（范围14至206）和83±65（范围24至570）pmol/mmol肌酐（P>.05）。在未治疗患者（r =.41，P <.001）和接受环氧化酶抑制剂治疗的患者（r =.31，P <.001）中，这两种代谢产物之间的相关性均为中等。在多元回归分析中，血栓素生成增加与入院时卒中严重程度、心房颤动以及环氧化酶抑制药物治疗独立相关。
我们得出结论，在急性缺血性卒中后的最初几天内：（1）血小板活化以环氧化酶依赖的方式反复发生；（2）血小板活化与异前列腺素生物合成的同时变化无关；（3）血小板活化与卒中严重程度和心房颤动独立相关；（4）异前列腺素生物合成在很大程度上独立于血小板环氧化酶活性。
