School of Medicine and Medical Sciences, Conway Institute, University College Dublin, Dublin, Ireland.
Anesthesiology. 2010 Jul;113(1):116-25. doi: 10.1097/ALN.0b013e3181dfd2fe.
Hypercapnic acidosis frequently occurs when patients with acute lung injury are initially ventilated with low tidal volume "protective" strategies. Hypercapnic acidosis per se, in the absence of any change in tidal volume or airway pressure, is protective when instituted before the onset of injury. However, the mechanisms by which hypercapnic acidosis confers this protection are incompletely understood, in particular, the effects on pulmonary oxidative reactions, which are potent mediators of tissue damage, have not been previously examined in vivo.
After anesthesia, tracheostomy, and the intratracheal instillation of endotoxin to establish lung injury, rats were mechanically ventilated for 6 h in normocapnia (21% O2, 0% CO2). Rats were then randomized to either normocapnic (21% O2, 0% CO2) or hypercapnic (21% O2, 5% CO2) ventilation and a nonspecific nitric oxide synthase inhibitor (N-monomethyl-L-arginine) or vehicle. Dihydrorhodamine was administered intravenously, and the lungs were removed for determination of the oxidative formation of rhodamine by spectrofluorimetry after 20 min. Thus, rats were randomly assigned to either: normocapnia-endotoxin (n = 12), normocapnia-endotoxin-N-monomethyl-L-arginine (n = 9), hypercapnia-endotoxin (n = 11), or hypercapnia-endotoxin-N-monomethyl-L-arginine (n = 10).
Hypercapnic acidosis significantly reduced the pulmonary oxidative reactions in the inflamed lung compared with normocapnia. Nitric oxide synthase blockade did not alter endotoxin-induced oxidative reactions.
Hypercapnic acidosis reduced oxidative reactions in the acutely injured lung in vivo, within minutes of onset and was not reliant on nitric oxide-dependent peroxynitrite production. This rapid onset antioxidant action is a previously undescribed mechanism by which hypercapnic acidosis could act, even when acute lung injury is well established.
急性肺损伤患者最初采用小潮气量“保护性”策略通气时，常发生高碳酸血症酸中毒。在损伤发生之前，即使潮气量或气道压力没有任何变化，单纯的高碳酸血症酸中毒本身也是保护性的。然而，高碳酸血症酸中毒产生这种保护作用的机制尚不完全清楚，特别是其对肺氧化反应的影响，肺氧化反应是组织损伤的有力介质，以前尚未在体内进行过检查。
麻醉、气管切开和气管内注入内毒素建立肺损伤后，大鼠在常氧（21%O2，0%CO2）下机械通气 6 小时。然后，大鼠随机分为常氧（21%O2，0%CO2）或高碳酸血症（21%O2，5%CO2）通气以及非特异性一氧化氮合酶抑制剂（N-单甲基-L-精氨酸）或载体。静脉给予二氢罗丹明，20 分钟后通过分光荧光法测定肺内罗丹明的氧化生成。因此，大鼠随机分为以下几组：常氧-内毒素（n=12）、常氧-内毒素-N-单甲基-L-精氨酸（n=9）、高碳酸血症-内毒素（n=11）或高碳酸血症-内毒素-N-单甲基-L-精氨酸（n=10）。
与常氧相比，高碳酸血症显著降低了炎症肺中的肺氧化反应。一氧化氮合酶阻断不改变内毒素诱导的氧化反应。
高碳酸血症酸中毒可降低急性损伤肺中的氧化反应，在损伤发生后数分钟内发生，且不依赖于一氧化氮依赖性过氧亚硝酸盐的产生。这种快速起始的抗氧化作用是以前未描述的高碳酸血症酸中毒作用机制，即使急性肺损伤已经确立。
