Effects of sildenafil analogue UK 343-664 on a porcine model of acute pulmonary hypertension
Effects of sildenafil analogue UK 343-664 on a porcine model of acute pulmonary hypertension
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DOI：
10.1016/s0003-4975(03)01489-9
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发表时间：
2004-01-01
影响因子：
4.6
通讯作者：
Lobato, EB
中科院分区：
文献类型：
--
作者：
Bonnell, MR;Urdaneta, F;Lobato, EB
背景西地那非（Pfizer Pharmaceuticals，Sandwich，肯特，英国）与肺血管舒张相关。已开发出更强效的西地那非类似物（UK 343-664 [Pfizer Pharmaceuticals]），但尚未研究其体内作用。本研究评价UK 343-664（辉瑞）在急性肺动脉高压中的作用。用1个最小肺泡浓度的异氟烷麻醉14只成年猪，并以50%的FIO 2进行机械通气。潮气末CO维持在32 - 36 mm Hg之间。将微压计尖端导管置于升主动脉、肺动脉和右心室中。肺血流测量与血管周围探头使用渡越时间超声。通过连续输注血栓烷类似物U46619诱导肺动脉高压。将动物随机分为两组。第1组（n=9）静脉注射500 μ g UK 343-664（Pfizer）超过2分钟。第2组（n=5）作为对照组。连续记录数据60分钟。采用方差分析和t检验进行统计学分析。P <0.05为有意义。所有动物均出现肺动脉高压。UK 343-664（Pfizer）给药与肺动脉压显著降低相关（30.3%; p
Background. Sildenafil (Pfizer Pharmaceuticals, Sandwich, Kent, UK) has been associated with pulmonary vasorelaxation. A more potent Sildenafil analogue (UK 343-664 [Pfizer Pharmaceuticals]) has been developed, but its effects in vivo have not been studied. This study evaluated the effects of UK 343-664 (Pfizer) during acute pulmonary hypertension.Methods. Fourteen adult swine were anesthetized with 1 minimum alveolar concentration isoflurane and were mechanically ventilated with an FIO2 of 50%. End tidal CO, was maintained between 32 and 36 mm Hg. Micro-manometer tipped catheters were placed in the ascending aorta, pulmonary artery, and right ventricle. Pulmonary flow was measured with a perivascular probe using transit time ultrasound. Pulmonary hypertension was induced with a continuous infusion of the thromboxane analogue U46619. Animals were randomized into two groups. Group 1 (n=9) received 500 mug of UK 343-664 (Pfizer) intravenously for more than 2 minutes. Group 2 (n=5) served as the control group. Data were recorded continuously for 60 minutes. Statistical analyses were performed with the analysis of variance and t tests. A p less than 0.05 was considered significant.Results. Pulmonary hypertension was achieved in all animals. The administration of UK 343-664 (Pfizer) was associated with a significant decrease in pulmonary artery pressure (30.3%; p