Wang Ling, Zhu Du Ming, Su Xiao, Bai Chun Xue, Ware Lorraine B, Matthay Michael A
Research Institute of Respiratory Diseases and Department of Surgical Intensive Care Unit, Zhongshan Hospital, Fudan University, Shanghai, China.
Exp Lung Res. 2004 Jan-Feb;30(1):31-42. doi: 10.1080/01902140490252821.
The objective of this study was to evaluate the cardiopulmonary effects of a dual-endothelin (ET) receptor antagonist, Tezosentan, on oleic acid (OA)-induced acute lung injury with pulmonary arterial hypertension in dogs. Twelve pentobarbital-anesthetized dogs with intravenous OA-induced acute lung injury (ALI) were divided into 2 groups. The control group (n=6) received saline treatment, whereas the treatment group (n=6) received the ET receptor antagonist, Tezosentan (1 mg/kg intravenous [i.v.]+1 mg/kg/h i.v. infusion). Cardiopulmonary parameters were monitored continuously for 1 hour. OA administration resulted in a significant increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR) and a decrease in mean systemic arterial pressure (MSAP), systemic vascular resistance (SVR), and cardiac output (CO) in all dogs. Tezosentan treatment markedly attenuated the pulmonary hypertension, with a 32% decrease in MPAP (from 23 +/- 2 mm Hg to 15 +/- 2 mm Hg; P<.01) and a 22% decrease in PVR (from 860 +/- 105 dyn.s.cm(-5) to 670 +/- 96 dyn.s.cm(-5); P<.01) at the end of study. MSAP and SVR were unchanged after Tezosentan treatment, and there was an increase in cardiac output and a decline in peak inspiratory pressure (PIP) in the Tezosentan group compared with the control group. These results indicate that the dual-ET receptor antagonist, Tezosentan, can attenuate the pulmonary hypertension induced by OA. Thus, dual-ET receptor antagonists such as Tezosentan may be useful in the management of acute pulmonary arterial hypertension, complicating the course of OA-induced lung injury.
本研究的目的是评估双重内皮素（ET）受体拮抗剂替唑生坦对油酸（OA）诱导的犬急性肺损伤伴肺动脉高压的心肺效应。将12只戊巴比妥麻醉的犬经静脉注射OA诱导急性肺损伤（ALI），分为2组。对照组（n = 6）接受生理盐水治疗，而治疗组（n = 6）接受ET受体拮抗剂替唑生坦（静脉注射1 mg/kg + 静脉输注1 mg/kg/h）。连续监测心肺参数1小时。所有犬静脉注射OA后，平均肺动脉压（MPAP）和肺血管阻力（PVR）显著升高，平均体动脉压（MSAP）、体循环血管阻力（SVR）和心输出量（CO）降低。替唑生坦治疗显著减轻了肺动脉高压，研究结束时MPAP降低了32%（从（23±2）mmHg降至（15±2）mmHg；P<0.01），PVR降低了22%（从（860±105）dyn·s·cm⁻⁵降至（670±96）dyn·s·cm⁻⁵；P<0.01）。替唑生坦治疗后MSAP和SVR未改变，与对照组相比，替唑生坦组心输出量增加，吸气峰压（PIP）下降。这些结果表明，双重ET受体拮抗剂替唑生坦可减轻OA诱导的肺动脉高压。因此，像替唑生坦这样的双重ET受体拮抗剂可能有助于治疗急性肺动脉高压，这是OA诱导的肺损伤过程中的并发症。
