Waerhaug Kristine, Kuzkov Vsevolod V, Kuklin Vladimir N, Mortensen Rica, Nordhus Kåre C, Kirov Mikhail Y, Bjertnaes Lars J
Department of Anesthesiology, Institute of Clinical Medicine, Faculty of Medicine, University of Tromsø, N-9037 Tromsø, Norway.
Crit Care. 2009;13(2):R51. doi: 10.1186/cc7777. Epub 2009 Apr 8.
We recently demonstrated that intravenously infused recombinant human activated protein C (APC) attenuates ovine lipopolysaccharide (LPS)-induced lung injury. In this study, our aim was to find out whether treatment with inhaled aerosolised APC (inhAPC) prevents formation of increased lung densities and oedema and derangement of oxygenation during exposure to LPS.
Sheep were anaesthetised during placement of intravascular introducers. After one to four days of recovery from instrumentation, the animals were re-anaesthetised, endotracheally intubated and mechanically ventilated throughout a six-hour experiment where the sheep underwent quantitative lung computed tomography. Sheep were randomly assigned to one of three groups: a sham-operated group (n = 8) receiving inhaled aerosolised saline from two hours after the start of the experiment; a LPS group (n = 8) receiving an intravenous infusion of LPS 20 ng/kg per hour and, after two hours, inhaled aerosolised saline over the next four hours; a LPS+inhAPC group (n = 8) receiving an intravenous infusion of LPS 20 ng/kg per hour and, after two hours, aerosolised APC 48 microg/kg per hour inhaled throughout the experiment. Data were analysed with analysis of variance; P less than 0.05 was regarded as significant.
An infusion of LPS was associated with a reduction of well-aerated lung volume and a rapid fall in arterial oxygenation that were both significantly antagonised by inhaled APC. Pulmonary vascular pressures and extravascular lung water index increased significantly during exposure to LPS, but inhaled APC had no effect on these changes.
Inhalation of aerosolised APC attenuates LPS-induced lung injury in sheep by preventing a decline in the volume of aerated lung tissue and improving oxygenation.
我们最近证明，静脉注射重组人活化蛋白C（APC）可减轻绵羊脂多糖（LPS）诱导的肺损伤。在本研究中，我们的目的是确定吸入雾化APC（inhAPC）治疗是否能预防LPS暴露期间肺密度增加、水肿形成以及氧合紊乱。
在放置血管内导管时对绵羊进行麻醉。在仪器植入后恢复1至4天，动物再次麻醉，气管插管并在整个6小时的实验过程中进行机械通气，在此期间对绵羊进行定量肺部计算机断层扫描。绵羊被随机分为三组之一：假手术组（n = 8），从实验开始后2小时起接受吸入雾化生理盐水；LPS组（n = 8），每小时静脉输注20 ng/kg LPS，并在2小时后，在接下来的4小时内吸入雾化生理盐水；LPS + inhAPC组（n = 8），每小时静脉输注20 ng/kg LPS，并在2小时后，在整个实验过程中每小时吸入48 μg/kg雾化APC。数据采用方差分析进行分析；P小于0.05被视为具有显著性。
输注LPS与通气良好的肺容积减少以及动脉氧合迅速下降有关，吸入APC可显著对抗这两者。在暴露于LPS期间，肺血管压力和血管外肺水指数显著增加，但吸入APC对这些变化没有影响。
吸入雾化APC可通过防止通气肺组织体积下降和改善氧合来减轻绵羊LPS诱导的肺损伤。
