Geiger Ralf, Kleinsasser Axel, Meier Stephan, Neu Nikolaus, Pajk Werner, Fischer Victoria, Treml Benedict, Stein Joerg I, Loeckinger Alexander
Innsbruck Medical University, Clinical Division of Pediatric Cardiology, Pulmology, Allergology and Cystic Fibrosis, Anichstrasse 35, 6020 Innsbruck, Austria.
Intensive Care Med. 2008 Feb;34(2):368-76. doi: 10.1007/s00134-007-0857-y. Epub 2007 Sep 27.
Meconium aspiration induces acute lung injury (ALI) and subsequent pulmonary arterial hypertension (PAH) which may lead to right ventricular failure. Increase of endothelin-1, thromboxane-A, and phosphodiesterases are discussed molecular mechanisms. We investigated the intrapulmonary and hemodynamic effects of the intravenous dual endothelin A and B receptor blocker tezosentan and inhalational iloprost in a model of ALI due to meconium aspiration.
Animal study.
University-affiliated research laboratory.
White farm pigs.
Acute lung injury was induced in 24 pigs by instillation of meconium. Animals were randomly assigned to four groups to receive either intravenous tezosentan, inhalational iloprost, or combined tezosentan and iloprost, or to serve as controls.
After meconium aspiration-induced lung injury each treatment increased oxyhemoglobin saturations (TEZO: 88 +/- 6% (p = 0.02), ILO: 85 +/- 13% (p = 0.05), TEZO-ILO: 89 +/- 6% (p = 0.02), control: 70 +/- 18%). TEZO but not ILO significantly decreased pulmonary arterial pressure and pulmonary vascular resistance (both p < 0.01). ILO alone decreased intrapulmonary shunt blood flow (p < 0.01). Compared with control, TEZO-ILO yielded the highest arterial partial pressure of oxygen (70 +/- 6 torr vs.49 +/- 9 torr, p = 0.04), although it decreased arterial blood pressure (change from 71 +/- 13 mmHg to 62 +/- 12 mmHg vs.85 +/- 14 mmHg to 80 +/- 11 mmHg (p = 0.01).
Intravenous TEZO improves pulmonary gas exchange and hemodynamics in experimental acute lung injury secondary to meconium aspiration. Inhaled ILO improves gas exchange only, thereby reducing intrapulmonary shunt blood flow. Combination of TEZO and ILO marginally improves pulmonary gas exchange at the disadvantage of pulmonary selectivity.
胎粪吸入可导致急性肺损伤（ALI）及随后的肺动脉高压（PAH），进而可能引发右心室衰竭。内皮素-1、血栓素-A和磷酸二酯酶的增加是相关分子机制。我们在胎粪吸入所致ALI模型中研究了静脉注射双重内皮素A和B受体阻滞剂替唑生坦及吸入伊洛前列素对肺内和血流动力学的影响。
动物研究。
大学附属研究实验室。
白色农场猪。
通过滴注胎粪在24头猪中诱导急性肺损伤。动物被随机分为四组，分别接受静脉注射替唑生坦、吸入伊洛前列素、联合使用替唑生坦和伊洛前列素，或作为对照组。
胎粪吸入所致肺损伤后，每种治疗均提高了氧合血红蛋白饱和度（替唑生坦组：88±6%（p = 0.02），伊洛前列素组：85±13%（p = 0.05），替唑生坦 - 伊洛前列素联合组：89±6%（p = 0.02），对照组：70±18%）。替唑生坦而非伊洛前列素显著降低了肺动脉压和肺血管阻力（两者p < 0.01）。单独使用伊洛前列素降低了肺内分流血流量（p < 0.01）。与对照组相比，替唑生坦 - 伊洛前列素联合组产生了最高的动脉血氧分压（70±6托 vs. 49±9托，p = 0.04），尽管其降低了动脉血压（从71±13 mmHg变为62±12 mmHg，而对照组从85±14 mmHg变为80±11 mmHg（p = 0.01））。
静脉注射替唑生坦可改善实验性胎粪吸入所致急性肺损伤中的肺气体交换和血流动力学。吸入伊洛前列素仅改善气体交换，从而减少肺内分流血流量。替唑生坦和伊洛前列素联合使用虽略微改善了肺气体交换，但以牺牲肺选择性为代价。
