Sommerer A, Kaisers U, Dembinski R, Bubser H P, Falke K J, Rossaint R
Abteilung X, Anaesthesiologie und Intensivmedizin, Bundeswehrkrankenhaus Berlin, Germany.
Intensive Care Med. 2000 Apr;26(4):434-41. doi: 10.1007/s001340051178.
To determine the dose-response relationship of almitrine (Alm) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI).
Prospective, randomized, controlled study.
Twenty anesthetized, tracheotomized and mechanically ventilated (FIO2 1.0) pigs underwent induction of ALI by repeated saline washout of surfactant. Animals were randomly assigned to either receive cumulating doses of Alm intravenously (0.5, 1.0, 2.0, 4.0, 8.0 and 16.0 micrograms.kg-1.min-1) for 30 min each (treatment; n = 10) or to receive the solvent malic acid (controls; n = 10).
Measurements of pulmonary gas exchange and hemodynamics were performed at the end of each infusion period. Alm < 4.0 micrograms.kg-1.min-1 improved arterial oxygen pressure (PaO2) (105 +/- 9 mmHg for Alm 1.0 vs 59 +/- 5 mmHg) and decreased intrapulmonary shunt (Qs/Qt) (32 +/- 4% for Alm 1.0 vs 46 +/- 4%) (P < 0.05). Alm > or = 8.0 micrograms.kg-1.min-1 did not improve pulmonary gas exchange compared to controls. When compared to low doses of Alm < 4.0 micrograms.kg-1.min-1, high doses > or = 8.0 micrograms.kg1.min-1 decreased PaO2 (58 +/- 11 mmHg for Alm 16.0) and increased Qs/Qt (67 +/- 10% for Alm 16.0) (P < 0.05).
In experimental ALI, effects of almitrine on oxygenation are dose-dependent. Almitrine is most effective when used at low doses known to mimic hypoxic pulmonary vasoconstriction.
在急性肺损伤（ALI）动物模型中确定烯丙哌三嗪（Alm）对肺气体交换和血流动力学的剂量反应关系。
前瞻性、随机、对照研究。
20只麻醉、气管切开并机械通气（吸入氧分数1.0）的猪，通过反复用盐水冲洗表面活性物质诱导ALI。动物被随机分为两组，一组静脉内接受累积剂量的Alm（0.5、1.0、2.0、4.0、8.0和16.0微克·千克⁻¹·分钟⁻¹），每组持续30分钟（治疗组；n = 10），另一组接受溶剂苹果酸（对照组；n = 10）。
在每个输注期结束时进行肺气体交换和血流动力学测量。Alm < 4.0微克·千克⁻¹·分钟⁻¹可改善动脉血氧分压（PaO₂）（Alm 1.0时为105±9 mmHg，而对照组为59±5 mmHg）并降低肺内分流（Qs/Qt）（Alm 1.0时为32±4%，而对照组为46±4%）（P < 0.05）。与对照组相比，Alm≥8.0微克·千克⁻¹·分钟⁻¹并未改善肺气体交换。与低剂量Alm < 4.0微克·千克⁻¹·分钟⁻¹相比，高剂量Alm≥8.0微克·千克⁻¹·分钟⁻¹会降低PaO₂（Alm 16.0时为58±11 mmHg）并增加Qs/Qt（Alm 16.0时为67±10%）（P < 0.05）。
在实验性ALI中，烯丙哌三嗪对氧合的作用是剂量依赖性的。当以模拟低氧性肺血管收缩的低剂量使用时，烯丙哌三嗪最为有效。
