Gelvez Javier, Fakioglu Harun, Olarte Jose L, Soliz Amed, Totapally Balagangadhar R, Torbati Dan
Division of Critical Care Medicine, Miami Children's Hospital, 3100 SW 62nd Avenue, Miami, FL 33156-3009, USA.
Pharmacol Res. 2004 Jul;50(1):87-91. doi: 10.1016/j.phrs.2003.12.005.
We tested whether aerosolized milrinone in lambs selectively reduces drug-induced acute pulmonary hypertension without reducing the mean systemic blood pressure (MSBP). Seven, 2-3-week-old lambs were anesthetized (50 mg/kg ketamine), paralyzed (0.1 mg/kg vecuronium bromide) and mechanically ventilated. A femoral artery, pulmonary artery, and jugular vein were catheterized for continuous monitoring of MSBP, mean pulmonary artery pressure, periodic gas-exchange analyses, and determination of cardiac output by thermodilution technique. An Airlife Misty nebulizer was used in a dry state to establish a stable baseline of an inspired fraction of oxygen (FiO(2)) at 0.21. Acute pulmonary hypertension with hypoxemia was then induced by increasing the mean pulmonary artery pressure up to 30-35% of the MSBP using 2-6 microg/kg/min of Thromboxane A(2) mimetic (U-46619), intravenously. The lambs were then subjected to 15 min of saline nebulization without milrinone followed by 30 min saline nebulization with a relatively high concentration of milrinone (10 mg/ml, total dose of 40 mg). Aerosolized milrinone had no effect on systemic or pulmonary artery pressure during combined acute pulmonary hypertension and hypoxemia. We speculate that our nebulization procedures failed to deliver sufficient amount of milrinone for producing a detectable hemodynamic effect.
我们测试了雾化米力农对羔羊是否能选择性降低药物诱导的急性肺动脉高压而不降低平均体循环血压（MSBP）。七只2 - 3周龄的羔羊接受麻醉（50mg/kg氯胺酮）、麻痹（0.1mg/kg维库溴铵）并进行机械通气。将一根股动脉、肺动脉和颈静脉插管，用于连续监测MSBP、平均肺动脉压、定期气体交换分析以及通过热稀释技术测定心输出量。使用处于干燥状态的Airlife Misty雾化器在吸入氧分数（FiO(2)）为0.21时建立稳定的基线。然后通过静脉注射2 - 6μg/kg/min的血栓素A(2)类似物（U - 46619）将平均肺动脉压升高至MSBP的30 - 35%来诱导伴有低氧血症的急性肺动脉高压。随后羔羊先接受15分钟无米力农的盐水雾化，接着接受30分钟较高浓度米力农（10mg/ml，总剂量40mg）的盐水雾化。在合并急性肺动脉高压和低氧血症期间，雾化米力农对体循环或肺动脉压没有影响。我们推测我们的雾化程序未能输送足够量的米力农以产生可检测到的血流动力学效应。
