Hypercapnic acidosis attenuates endotoxin-induced acute lung injury
Hypercapnic acidosis attenuates endotoxin-induced acute lung injury
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DOI：
10.1164/rccm.200205-394oc
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发表时间：
2004-01-01
影响因子：
24.7
通讯作者：
McLoughlin, P
中科院分区：
文献类型：
--
作者：
Laffey, JG;Honan, D;McLoughlin, P
在活体缺血-再灌注和机械通气诱导的肺损伤后，有意诱导的预防性高碳酸酸中毒可保护肺损伤。然而，高碳酸血症对败血症的疗效尚不清楚，败血症是临床急性呼吸窘迫综合征的最常见原因。我们研究了在活体大鼠模型中，通过向吸入气体中添加二氧化碳而引起的高碳酸中毒是否对内毒素诱导的肺损伤具有保护作用。与对照组相比，预防高碳酸血症(即在内毒素滴注前进行诱导)可减轻动脉血氧分压的降低，改善肺顺应性，并减轻肺泡中性粒细胞的浸润。高碳酸血症的治疗机制，即内毒素滴注后诱导，可减轻氧合下降，改善肺顺应性，减少肺泡中性粒细胞浸润，减少肺损伤的组织学指标。治疗性高碳酸中毒减轻了内毒素引起的肺组织和上皮衬里液体中氮和亚硝硫醇的高级氧化物的增加。高碳酸血症时，肺上皮细胞衬里液中硝基酪氨酸浓度升高。我们的结论是，高碳酸血症减轻了急性内毒素所致的肺损伤，在预防和治疗方面都是有效的。高碳酸中毒的有益作用不是通过抑制过氧亚硝酸盐诱导的蛋白质内硝化来实现的。
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.