School of Medicine, Clinical Sciences Institute, National University of Ireland, Galway, Ireland.
Crit Care Med. 2012 Sep;40(9):2622-30. doi: 10.1097/CCM.0b013e318258f8b4.
Hypercapnic acidosis protects against ventilation-induced lung injury. We wished to determine whether the beneficial effects of hypercapnic acidosis in reducing stretch-induced injury were mediated via inhibition of nuclear factor-κB, a key transcriptional regulator in inflammation, injury, and repair.
Prospective randomized animal study.
University research laboratory.
Adult male Sprague-Dawley rats.
In separate experimental series, the potential for hypercapnic acidosis to attenuate moderate and severe ventilation-induced lung injury was determined. In each series, following induction of anesthesia and tracheostomy, Sprague-Dawley rats were randomized to (normocapnia; FICO2 0.00) or (hypercapnic acidosis; FICO2 0.05), subjected to high stretch ventilation, and the severity of lung injury and indices of activation of the nuclear factor-κB pathway were assessed. Subsequent in vitro experiments examined the potential for hypercapnic acidosis to reduce pulmonary epithelial inflammation and injury induced by cyclic mechanical stretch. The role of the nuclear factor-κB pathway in hypercapnic acidosis-mediated protection from stretch injury was then determined.
Hypercapnic acidosis attenuated moderate and severe ventilation-induced lung injury, as evidenced by improved oxygenation, compliance, and reduced histologic injury compared to normocapnic conditions. Hypercapnic acidosis reduced indices of inflammation such as interleukin-6 and bronchoalveolar lavage neutrophil infiltration. Hypercapnic acidosis reduced the decrement of the nuclear factor-κB inhibitor IκBα and reduced the generation of cytokine-induced neutrophil chemoattractant-1. Hypercapnic acidosis reduced cyclic mechanical stretch-induced nuclear factor-κB activation, reduced interleukin-8 production, and decreased epithelial injury and cell death compared to normocapnia.
Hypercapnic acidosis attenuated ventilation-induced lung injury independent of injury severity and decreased mechanical stretch-induced epithelial injury and death, via a nuclear factor-κB-dependent mechanism.
高碳酸酸中毒可预防通气引起的肺损伤。我们希望确定高碳酸酸中毒通过抑制核因子-κB（炎症、损伤和修复的关键转录调节剂）减少牵张诱导损伤的有益作用是否是通过这种方式实现的。
前瞻性随机动物研究。
大学研究实验室。
成年雄性 Sprague-Dawley 大鼠。
在单独的实验系列中，确定高碳酸酸中毒是否能够减轻中度和重度通气引起的肺损伤。在每个系列中，在诱导麻醉和气管切开后，Sprague-Dawley 大鼠被随机分配到（正常碳酸血症；FICO2 0.00）或（高碳酸血症；FICO2 0.05），然后进行高牵张通气，并评估肺损伤的严重程度和核因子-κB 途径的激活指标。随后的体外实验研究了高碳酸酸中毒降低周期性机械牵张引起的肺上皮炎症和损伤的潜力。然后确定核因子-κB 途径在高碳酸酸中毒介导的牵张损伤保护中的作用。
与正常碳酸血症相比，高碳酸酸中毒减轻了中度和重度通气引起的肺损伤，表现为氧合、顺应性改善和组织学损伤减少。高碳酸酸中毒降低了白细胞介素-6 和支气管肺泡灌洗中性粒细胞浸润等炎症指标。高碳酸酸中毒降低了核因子-κB 抑制剂 IκBα 的减少，并减少了细胞因子诱导的中性粒细胞趋化因子-1 的生成。与正常碳酸血症相比，高碳酸酸中毒降低了周期性机械牵张诱导的核因子-κB 激活、白细胞介素-8 的产生，并减少了上皮损伤和细胞死亡。
高碳酸酸中毒减轻了通气引起的肺损伤，与损伤严重程度无关，并通过核因子-κB 依赖性机制减少了机械牵张引起的上皮损伤和死亡。
