Soluri-Martins André, Moraes Lillian, Santos Raquel S, Santos Cintia L, Huhle Robert, Capelozzi Vera L, Pelosi Paolo, Silva Pedro L, de Abreu Marcelo Gama, Rocco Patricia R M
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de JaneiroRio de Janeiro, Brazil.
Pulmonary Engineering Group, Department of Anesthesiology and Intensive Care Therapy, University Hospital Carl Gustav Carus, Dresden University of TechnologyDresden, Germany.
Front Physiol. 2017 May 2;8:257. doi: 10.3389/fphys.2017.00257. eCollection 2017.
Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV) in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV vs. VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and (2) Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV ( = 6/group) [tidal volume (V) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 2 cmHO, fraction of inspired oxygen (FiO) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated V values ( = 1200; mean V = 6 mL/kg), with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final), respiratory system mechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean ± SD, VCV 3.6 ± 1.3 cmH0/ml and 2.0 ± 0.8 cmH0/ml, = 0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8], = 0.04, respectively). In left lungs of IR animals, VCV increased the expression of interleukin-6 and intercellular adhesion molecule-1 compared to NV, with no significant differences between VV and NV. Compared to VCV, VV increased the expression of surfactant protein-D, suggesting protection from type II epithelial cell damage. In conclusion, in this experimental lung ischemia-reperfusion model, VV improved respiratory system elastance and reduced lung damage compared to VCV.
肺缺血再灌注损伤仍然是肺移植后的主要并发症。在由内毒素、盐水灌洗导致的表面活性剂耗竭以及盐酸诱导的不同肺损伤模型中，与保护性容量控制通气（VCV）相比，可变通气（VV）已被证明可改善呼吸功能并减少肺部组织学损伤。然而，尚无研究比较VV与VCV在肺缺血再灌注损伤中的生物学影响，肺缺血再灌注损伤具有与其他实验模型不同的复杂病理生理学。36只动物被随机分为两组之一：（1）缺血再灌注（IR）组，其中左肺门完全闭塞30分钟后再松开；（2）假手术组，动物接受相同的手术操作，但不进行肺门钳夹。手术后立即从每组6只动物中取出左（IR损伤）肺和右（对侧）肺，作为未通气组（NV）用于分子生物学分析。IR组和假手术组进一步随机分为两种通气策略之一：VCV（每组 = 6只）[潮气量（V）= 6 mL/kg，呼气末正压（PEEP）= 2 cmH₂O，吸入氧分数（FiO₂）= 0.4]；或VV，以逐次呼吸为基础应用一系列随机生成的V值（ = 1200；平均V = 6 mL/kg），变异系数为30%。通气5分钟后以及2小时末（最终），测量呼吸系统力学和动脉血气。在最终时，取出肺进行组织学和分子生物学分析。VCV组的呼吸系统弹性和肺泡萎陷低于VV组（平均值±标准差，VCV组为3.6±1.3 cmH₂O/ml和2.0±0.8 cmH₂O/ml，P = 0.005；中位数[四分位间距]，VCV组为20.4%[7.9 - 33.1]，VV组为5.4%[3.1 - 8.8]，P = 0.04）。在IR动物的左肺中，与NV组相比，VCV组白细胞介素-6和细胞间黏附分子-1的表达增加，VV组与NV组之间无显著差异。与VCV组相比，VV组表面活性蛋白-D的表达增加，提示对II型上皮细胞损伤有保护作用。总之，在这个实验性肺缺血再灌注模型中，与VCV相比，VV改善了呼吸系统弹性并减少了肺损伤。
