Deb B, Bradford K, Pearl R G
Department of Anesthesia, Stanford University Medical Center, CA 94305-5117, USA.
Crit Care Med. 2000 Mar;28(3):795-9. doi: 10.1097/00003246-200003000-00031.
To determine whether inhaled nitric oxide (IN0) and intravenous milrinone have additive pulmonary vasodilator effects in a rat model of pulmonary hypertension.
Prospective, experimental study.
Animal laboratory of a university medical center.
Male New Zealand White rabbits.
Anesthetized rabbits were mechanically ventilated and instrumented for measurement of systemic mean arterial pressure (MAP), pulmonary artery pressure (PAP), left atrial pressure, and cardiac output (CO). After baseline measurements, the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg iv) was administered. Pulmonary hypertension was produced by the continuous infusion of U46619, a thromboxane A2 mimetic. INO (40 ppm) was added to the inspired gas, and hemodynamic measurements were obtained before and after INO. Milrinone was administered sequentially as a 30-mg/kg bolus followed by a 3-microg/kg/min infusion, a 100-mg/kg bolus followed by a 10-microg/kg/min infusion, and a 300-mg/kg bolus followed by a 30-microg/kg/min infusion (M3). Hemodynamic measurements were obtained with and without INO at each dose of milrinone.
During U46619-induced pulmonary hypertension, INO decreased PAP and pulmonary vascular resistance (PVR) but did not affect MAP, systemic vascular resistance (SVR), or CO. Milrinone dose dependently decreased PAP, PVR, MAP, and SVR and increased CO. At each dose of milrinone, INO further decreased PVR but not SVR. M3 decreased PVR 49%, and the addition of INO decreased PVR an additional 19% so that PAP and PVR decreased to baseline values.
Milrinone and INO both decrease pulmonary hypertension individually, and the combination produces additive effects. Combination therapy may produce potent and selective pulmonary vasodilation during the treatment of pulmonary hypertension.
确定在大鼠肺动脉高压模型中，吸入一氧化氮（INO）与静脉注射米力农是否具有相加的肺血管舒张作用。
前瞻性实验研究。
大学医学中心的动物实验室。
雄性新西兰白兔。
对麻醉的兔子进行机械通气，并安装仪器以测量体循环平均动脉压（MAP）、肺动脉压（PAP）、左心房压和心输出量（CO）。在进行基线测量后，给予一氧化氮合酶抑制剂N（G）-硝基-L-精氨酸甲酯（30mg/kg静脉注射）。通过持续输注血栓素A2类似物U46619诱导产生肺动脉高压。将INO（40ppm）添加到吸入气体中，并在吸入INO前后进行血流动力学测量。依次给予米力农，先静脉推注30mg/kg，随后以3μg/kg/min的速度输注；再静脉推注100mg/kg，随后以10μg/kg/min的速度输注；最后静脉推注300mg/kg，随后以30μg/kg/min的速度输注（M3）。在每个米力农剂量下，分别在有和没有INO的情况下进行血流动力学测量。
在U46619诱导的肺动脉高压期间，INO降低了PAP和肺血管阻力（PVR），但不影响MAP、体循环血管阻力（SVR）或CO。米力农剂量依赖性地降低了PAP、PVR、MAP和SVR，并增加了CO。在每个米力农剂量下，INO进一步降低了PVR，但未降低SVR。M3使PVR降低了49%，添加INO后PVR又额外降低了19%，从而使PAP和PVR降至基线值。
米力农和INO均可单独降低肺动脉高压，两者联合使用具有相加作用。联合治疗在肺动脉高压治疗期间可能产生强效且选择性的肺血管舒张作用。
