Ketabchi Farzaneh, Egemnazarov Bakytbek, Schermuly Ralph T, Ghofrani Hossein A, Seeger Werner, Grimminger Friedrich, Shid-Moosavi Mostafa, Dehghani Gholam A, Weissmann Norbert, Sommer Natascha
School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Am J Physiol Lung Cell Mol Physiol. 2009 Nov;297(5):L977-83. doi: 10.1152/ajplung.00074.2009. Epub 2009 Aug 28.
Acute respiratory disorders and permissive hypercapnic strategy may lead to alveolar hypoxia and hypercapnic acidosis. However, the effects of hypercapnia with or without acidosis on hypoxic pulmonary vasoconstriction (HPV) and oxygen diffusion capacity of the lung are controversial. We investigated the effects of hypercapnic acidosis and hypercapnia with normal pH (pH corrected with sodium bicarbonate) on HPV, capillary permeability, gas exchange, and ventilation-perfusion matching in the isolated ventilated-perfused rabbit lung. No alteration in vascular tone was noted during normoxic hypercapnia with or without acidosis compared with normoxic normocapnia. Hypercapnia with normal pH resulted in a transient increase in HPV during the course of consecutive ventilation maneuvers, whereas hypercapnic acidosis increased HPV over time. Hypercapnic acidosis decreased exhaled NO during hypoxia more than hypercapnia with normal pH and normocapnia, whereas intravascular NO release was unchanged. However, inhibition of NO synthesis by nitro-L-arginine (L-NNA) resulted in a loss of the increased HPV caused by hypercapnic acidosis but not that caused by hypercapnia with normal pH. Furthermore, capillary permeability increased during hypoxic hypercapnia with normal pH but not hypoxic hypercapnic acidosis. This effect was NO-dependent because it disappeared during L-NNA administration. Ventilation-perfusion matching and arterial PO2 were improved according to the strength of HPV in hypercapnia compared with normocapnia during Tween nebulization-induced lung injury. In conclusion, the increased HPV during hypercapnic acidosis is beneficial to lung gas exchange by improving ventilation-perfusion matching and preserving the capillary barrier function. These effects seem to be linked to NO-mediated pathways.
急性呼吸障碍和允许性高碳酸血症策略可能导致肺泡缺氧和高碳酸性酸中毒。然而，伴有或不伴有酸中毒的高碳酸血症对低氧性肺血管收缩（HPV）和肺氧弥散能力的影响存在争议。我们研究了高碳酸性酸中毒以及pH值正常（用碳酸氢钠校正pH）的高碳酸血症对离体通气灌注兔肺的HPV、毛细血管通透性、气体交换和通气-灌注匹配的影响。与常氧常碳酸血症相比，在伴有或不伴有酸中毒的常氧高碳酸血症期间未观察到血管张力的改变。pH值正常的高碳酸血症在连续通气操作过程中导致HPV短暂增加，而高碳酸性酸中毒则使HPV随时间增加。与pH值正常的高碳酸血症和常碳酸血症相比，高碳酸性酸中毒在缺氧期间使呼出的一氧化氮（NO）减少更多，而血管内NO释放未改变。然而，用硝基-L-精氨酸（L-NNA）抑制NO合成导致高碳酸性酸中毒引起的HPV增加消失，但pH值正常的高碳酸血症引起的HPV增加未消失。此外，pH值正常的低氧高碳酸血症期间毛细血管通透性增加，而低氧高碳酸性酸中毒期间则未增加。这种效应依赖于NO，因为在给予L-NNA期间它消失了。在吐温雾化诱导的肺损伤期间，与常碳酸血症相比，高碳酸血症时通气-灌注匹配和动脉血氧分压（PO2）根据HPV的强度得到改善。总之，高碳酸性酸中毒期间HPV增加通过改善通气-灌注匹配和维持毛细血管屏障功能对肺气体交换有益。这些效应似乎与NO介导的途径有关。
