Gennai Stéphane, Souilamas Redha, Maignan Maxime, Brouta Angélique, Pison Christophe, Fontaine Eric, Briot Raphaël
Emergency Department, Grenoble University Hospital, Grenoble Cedex, France; TIMC IMAG Laboratory, UMR 5525, La Tronche Cedex, France.
Microcirculation. 2014 Jan;21(1):84-92. doi: 10.1111/micc.12082.
Several works highlight the role of CsA in the prevention of IRI, but none focus on isolated lungs. Our objective was to evaluate the effects of CsA on IRI on ex vivo reperfused pig lungs.
Thirty-two pairs of pig lungs were collected and stored for 30 minutes at 4 °C. The study was performed in four groups. First, a control group and then three groups receiving different concentrations of CsA (1, 10, and 30 μM) at two different times: once at the moment of lung procurement and another during the reperfusion procedure. The ex vivo lung preparation was set up using an extracorporeal perfusion circuit. Gas exchange parameters, pulmonary hemodynamics, and biological markers of lung injury were collected for the evaluation.
CsA improved the PaO2 /FiO2 ratio, but it also increased PAP, Pcap, and pulmonary vascular resistances with dose-dependent effects. Lungs treated with high doses of CsA displayed higher capillary-alveolar permeability to proteins, lower AFC capacities, and elevated concentrations of pro-inflammatory cytokines.
These data suggest a possible deleterious imbalance between the beneficial cell properties of CsA in IRI and its hemodynamic effects on microvascularization.
多项研究强调了环孢素A(CsA)在预防缺血再灌注损伤(IRI)中的作用,但均未聚焦于离体肺。我们的目的是评估CsA对体外再灌注猪肺IRI的影响。
收集32对猪肺并在4℃下保存30分钟。研究分为四组进行。首先是对照组,然后是三组在两个不同时间接受不同浓度CsA(1、10和30μM)的组:一次在肺获取时,另一次在再灌注过程中。使用体外灌注回路建立离体肺制备。收集气体交换参数、肺血流动力学和肺损伤生物标志物进行评估。
CsA改善了动脉血氧分压/吸入氧分数值(PaO2/FiO2)比值,但也增加了肺动脉压(PAP)、肺毛细血管压(Pcap)和肺血管阻力,且具有剂量依赖性效应。高剂量CsA处理的肺对蛋白质的毛细血管-肺泡通透性更高,肺泡灌洗细胞(AFC)能力更低,促炎细胞因子浓度升高。
这些数据表明,CsA在IRI中的有益细胞特性与其对微血管化的血流动力学效应之间可能存在有害的失衡。