Urdaneta Felipe, Willert Jessica L, Beaver Thomas, Naik Bhiken, Kirby David S, Lobato Emilio B
Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida 32610-0254, USA.
Ann Thorac Surg. 2004 Oct;78(4):1433-7. doi: 10.1016/j.athoracsur.2004.04.039.
Perioperative pulmonary hypertension remains a clinical challenge. The phosphodiesterase enzyme type III inhibitor milrinone produces pulmonary vasodilation but lacks selectivity. Sildenafil, a phosphodiesterase enzyme type V inhibitor, can also induce relaxation of the pulmonary vasculature; however, only the oral formulation is presently available. This study evaluated the effects of a new intravenous sildenafil analogue--UK 343-664--compared with milrinone during acute pulmonary hypertension in a porcine model of thromboxane-induced pulmonary hypertension.
After acute pulmonary hypertension, 24 adult swine were randomized to 3 groups. Group 1 (n = 9) received an intravenous dose of 500 microg of UK 343-664, group 2 (n = 8) received milrinone 50 mg/kg, and group 3 (n = 7) received 10 mL of normal saline solution. All agents were administered for more than 5 minutes. Data were recorded continuously for 30 minutes.
Both milrinone and UK 343-664 partially reversed thromboxane-induced pulmonary hypertension, with a notable decrease in mean pulmonary artery pressure and pulmonary vascular resistance and a concomitant increase in cardiac output. In addition, milrinone improved right ventricular contractility but produced marked systemic vasodilatation. In contrast, the administration of UK 343-664 was associated with pulmonary vasodilatation, without appreciable changes in systemic arterial pressure or vascular resistance.
Milrinone and UK 343-664 were equally effective as pulmonary vasodilators; however, only UK 343-664 exhibited a high degree of pulmonary selectivity. Potential uses for this new phosphodiesterase enzyme type V inhibitor warrant further study.
围手术期肺动脉高压仍然是一项临床挑战。Ⅲ型磷酸二酯酶抑制剂米力农可产生肺血管舒张作用，但缺乏选择性。Ⅴ型磷酸二酯酶抑制剂西地那非也可诱导肺血管舒张；然而，目前仅有口服制剂。本研究在血栓素诱导的肺动脉高压猪模型中，评估了一种新型静脉用西地那非类似物——UK 343-664——与米力农相比在急性肺动脉高压时的作用。
急性肺动脉高压形成后，将24只成年猪随机分为3组。第1组（n = 9）静脉注射500微克UK 343-664，第2组（n = 8）静脉注射米力农50毫克/千克，第3组（n = 7）静脉注射10毫升生理盐水。所有药物均持续输注5分钟以上。连续记录30分钟的数据。
米力农和UK 343-664均可部分逆转血栓素诱导的肺动脉高压，平均肺动脉压和肺血管阻力显著降低，心输出量随之增加。此外，米力农改善右心室收缩力，但可导致明显的全身血管舒张。相比之下，UK 343-664的应用与肺血管舒张相关，全身动脉压或血管阻力无明显变化。
米力农和UK 343-664作为肺血管舒张剂同样有效；然而，只有UK 343-664表现出高度的肺选择性。这种新型Ⅴ型磷酸二酯酶抑制剂的潜在用途值得进一步研究。
