Buffering hypercapnic acidosis worsens acute lung injury
Buffering hypercapnic acidosis worsens acute lung injury
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DOI：
10.1164/ajrccm.161.1.9905080
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发表时间：
2000-01-01
影响因子：
24.7
通讯作者：
Kavanagh, BP
中科院分区：
文献类型：
--
作者：
Laffey, JG;Engelberts, D;Kavanagh, BP
与高碳酸酸中毒（HCA）相关的通气不足可能改善急性肺损伤（ALI）的结局。我们最近报道了HCA本身可以预防ALI。目前的研究探讨了HCA的保护机制是否与酸中毒和高碳酸血症有关。由于CO2在细胞膜上迅速平衡，我们假设（1）HCA将比代谢性酸中毒提供更大的保护。我们进一步假设（2）缓冲HCA会减弱其保护作用。将40只离体灌注兔肺制备物随机分配至：对照组（正常pH，P-CO2）; HCA;代谢性酸中毒;或缓冲性高碳酸血症。缺血再灌注损伤后，对照组和缓冲性高碳酸血症组的湿干比最大，毛细血管滤过系数的大小顺序为：对照组接近缓冲性高碳酸血症组>代谢性酸中毒组> HCA组。缓冲性高碳酸血症的等重压力降低最大。尽管损伤相似，但缓冲性高碳酸血症组肺动脉压升高较对照组低。体外黄嘌呤氧化酶（XO）活性依赖于pH值，而不是P-CO2。我们的结论是：（1）HCA和代谢性酸中毒具有保护作用，但HCA的保护作用最强;（2）缓冲HCA减弱其保护作用;（3）缓冲HCA导致肺血管舒张;（4）由于代谢性酸中毒和HCA类似地抑制体外XO活性，因此不能仅根据细胞外XO活性来解释差异效应。
Hypoventilation, associated with hypercapnic acidosis (HCA), may improve outcome in acute lung injury (ALI). We have recently reported that HCA per se protects against ALI. The current study explored whether the mechanisms of protection with HCA were related to acidosis versus hypercapnia. Because CO2 equilibrates rapidly across cell membranes, we hypothesized that (1) HCA would afford greater protection than metabolic acidosis. We further hypothesized that (2) buffering HCA would attenuate its protection. Forty isolated perfused rabbit lung preparations were randomized to: control (normal pH, P-CO2); HCA; metabolic acidosis; or buffered hypercapnia. After ischemia-reperfusion (IR) injury wet:dry ratio was greatest with control and buffered hypercapnia, and rank order of capillary filtration coefficient was: control approximate to buffered hypercapnia > metabolic acidosis > HCA. Isogravi-metric pressure reduction was greatest with buffered hypercapnia. Despite comparable injury, pulmonary artery pressure elevation was less with buffered hypercapnia versus control. In vitro xanthine oxidase (XO) activity depended on pH, not P-CO2. We conclude that: (1) HCA and metabolic acidosis are protective, but HCA is the most protective; (2) buffering HCA attenuates its protection; (3) buffering HCA causes pulmonary vasodilation; (4) because metabolic acidosis and HCA similarly inhibit in vitro XO activity, the differential effects cannot be explained solely on the basis of extracellular XO activity.