Effect of BM-573[N-terbutyl-N′-[2-(4′-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a dual thromboxane synthase inhibitor and thromboxane receptor antagonist, in a porcine model of acute pulmonary embolism
Effect of BM-573[N-terbutyl-N′-[2-(4′-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a dual thromboxane synthase inhibitor and thromboxane receptor antagonist, in a porcine model of acute pulmonary embolism
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DOI：
10.1124/jpet.104.066852
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发表时间：
2004-09-01
影响因子：
3.5
通讯作者：
D'Orio, V
中科院分区：
文献类型：
--
作者：
Ghuysen, A;Lambermont, B;D'Orio, V
本研究的目的是评估双重血栓素 A(2) 合酶抑制剂和受体拮抗剂 BM-573 [N-叔丁基-N'-[2-(4'-甲基苯氨基)-5-硝基苯磺酰基]脲]对急性肺栓塞血流动力学反应的影响。六头麻醉猪被注射安慰剂（安慰剂组），并与其他六头接受连续注射 BM-573 的猪（BM 组）进行比较。输注开始后30分钟，用0.3g/kg自体血凝块进行肺栓塞。使用电导导管记录右心室压力-容量环，并通过改变右心室前负荷定期评估收缩末期心室弹性。使用四元风凯塞尔模型研究肺血管特性。血流动力学数据，包括右心室-动脉耦合的评估，在基线时收集，并在 4 小时内每 30 分钟收集一次。收集血样以评估气体交换、血栓素 A(2) 和前列环素血浆水平并评估血小板聚集。安慰剂组的平均肺动脉压比 BM 组显着增加，主要是因为肺血管阻力额外增加。安慰剂组的动脉和收缩末期心室弹性也增加更多，而右心室效率下降。 BM-573 可防止由 U-46619（9,11-双脱氧-11α、9α-环氧甲基前列腺素 F-2α）或花生四烯酸诱导的血小板聚集，以及血栓素 A(2) 的过量产生，而保留前列环素的释放。然而，氧合并没有显着改善。我们得出的结论是，在这种急性肺栓塞动物模型中，输注 BM-573 可减少肺血管收缩。结果，右心室-血管耦合值保持在最大效率水平。
The aim of this study was to evaluate the effect of BM-573 [N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a dual thromboxane A(2) synthase inhibitor and receptor antagonist, on the hemodynamic response to acute pulmonary embolism. Six anesthetized pigs were infused with placebo ( placebo group) and compared with six other pigs receiving a continuous infusion of BM-573 ( BM group). Pulmonary embolization with 0.3 g/kg autologous blood clots was carried out 30 min after the start of the infusion. Right ventricular pressure-volume loops were recorded using a conductance catheter, and end-systolic ventricular elastance was periodically assessed by varying right ventricular preload. Pulmonary vascular properties were studied by use of a four-element wind-kessel model. Hemodynamic data, including assessment of right ventricular-arterial coupling, were collected at baseline and every 30 min for 4 h. Blood samples were collected to assess gas exchange, thromboxane A(2), and prostacyclin plasma levels and to evaluate platelet aggregation. Mean pulmonary arterial pressure in the placebo group increased significantly more than in the BM group, mainly because of an additional increase in pulmonary vascular resistance. Arterial and end-systolic ventricular elastances increased also more in the placebo group, whereas right ventricular efficiency decreased. BM-573 prevented both platelet aggregation induced by U-46619 (9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F-2alpha) or by arachidonic acid, and thromboxane A(2) overproduction, whereas prostacyclin liberation was preserved. Oxygenation, however, was not significantly improved. We conclude that in this animal model of acute pulmonary embolism, infusion of BM-573 reduced pulmonary vasoconstriction. As a result, right ventricular-vascular coupling values were maintained at a maximal efficiency level.