Laffey John G, Honan Dave, Hopkins Natalie, Hyvelin Jean-Marc, Boylan John F, McLoughlin Paul
Department of Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
Am J Respir Crit Care Med. 2004 Jan 1;169(1):46-56. doi: 10.1164/rccm.200205-394OC. Epub 2003 Sep 4.
Deliberate induction of prophylactic hypercapnic acidosis protects against lung injury after in vivo ischemia-reperfusion and ventilation-induced lung injury. However, the efficacy of hypercapnic acidosis in sepsis, the commonest cause of clinical acute respiratory distress syndrome, is not known. We investigated whether hypercapnic acidosis--induced by adding CO2 to inspired gas--would be protective against endotoxin-induced lung injury in an in vivo rat model. Prophylactic institution of hypercapnic acidosis (i.e., induction before endotoxin instillation) attenuated the decrement in arterial oxygenation, improved lung compliance, and attenuated alveolar neutrophil infiltration compared with control conditions. Therapeutic institution of hypercapnic acidosis, that is, induction after endotoxin instillation, attenuated the decrement in oxygenation, improved lung compliance, and reduced alveolar neutrophil infiltration and histologic indices of lung injury. Therapeutic hypercapnic acidosis attenuated the endotoxin-induced increase in the higher oxides of nitrogen and nitrosothiols in the lung tissue and epithelial lining fluid. Lung epithelial lining fluid nitrotyrosine concentrations were increased with hypercapnic acidosis. We conclude that hypercapnic acidosis attenuates acute endotoxin-induced lung injury, and is efficacious both prophylactically and therapeutically. The beneficial actions of hypercapnic acidosis were not mediated by inhibition of peroxynitrite-induced nitration within proteins.
刻意诱导预防性高碳酸血症酸中毒可预防体内缺血再灌注和通气诱导的肺损伤后的肺损伤。然而，高碳酸血症酸中毒在临床急性呼吸窘迫综合征最常见的病因——脓毒症中的疗效尚不清楚。我们研究了在体内大鼠模型中，通过向吸入气体中添加二氧化碳诱导的高碳酸血症酸中毒是否能预防内毒素诱导的肺损伤。与对照情况相比，预防性建立高碳酸血症酸中毒（即在注入内毒素之前诱导）可减轻动脉氧合的下降，改善肺顺应性，并减轻肺泡中性粒细胞浸润。治疗性建立高碳酸血症酸中毒，即在注入内毒素之后诱导，可减轻氧合的下降，改善肺顺应性，并减少肺泡中性粒细胞浸润和肺损伤的组织学指标。治疗性高碳酸血症酸中毒可减轻内毒素诱导的肺组织和上皮衬液中氮的高价氧化物和亚硝基硫醇的增加。高碳酸血症酸中毒会使肺上皮衬液中的硝基酪氨酸浓度升高。我们得出结论，高碳酸血症酸中毒可减轻急性内毒素诱导的肺损伤，且在预防和治疗方面均有效。高碳酸血症酸中毒的有益作用并非通过抑制蛋白质内过氧亚硝酸盐诱导的硝化作用介导。
