Graduate Institute of Clinical Medical Sciences, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
J Surg Res. 2011 May 15;167(2):e77-83. doi: 10.1016/j.jss.2009.10.041. Epub 2009 Nov 24.
Post-cardiopulmonary bypass (CPB) lung injury is the combination of whole body inflammatory response and local ischemia-reperfusion (IR) injury. We investigated the benefit of pulmonary perfusion with L-arginine in protection against post-CPB lung injury.
New Zealand white rabbits (n = 50, weight, 2.5-2.8 kg) were divided into five groups (n = 10 each): sham (sham sternotomy), CPB (CPB without pulmonary perfusion), perfusion (CPB with pulmonary perfusion), L-arginine (CPB with perfusion + L-arginine), and L-NAME (CPB with perfusion + L-NAME). The duration of CPB was 60 min followed by 2 h of reperfusion. Pulmonary perfusion was performed every 20 min through the pulmonary artery during CPB. Checking parameters included: (1) pulmonary vascular resistance, (2) pulmonary artery endothelium relaxation (organ chamber study), and (3) IR marker (myeloperoxidase) and inflammatory markers (TNF-α, IL-B, NF-κB).
CPB induced pulmonary artery endothelium dysfunction manifested by increased pulmonary vascular resistance and impaired pulmonary artery relaxation. Pulmonary perfusion could significantly reverse the phenomenon (P < 0.01) while provision of NO precursor-L-arginine with pulmonary perfusion together further possessed significant relaxation ability for pulmonary arterial endothelium compared with perfusion alone (P < 0.05). Accordingly, lung parenchyma myeloperoxidase activity and inflammatory cytokine level were also markedly increased after CPB (P < 0.05). Pulmonary perfusion could partially decrease the response, whereas additional L-arginine further attenuated inflammatory cytokine release (P < 0.05).
Pulmonary perfusion during CPB partially ameliorates CPB-induced lung injury. Pulmonary perfusion with L-arginine could further attenuate lung injury by restoring endothelial function and decreasing inflammatory response.
体外循环（CPB）后肺损伤是全身炎症反应和局部缺血再灌注（IR）损伤的结合。我们研究了用 L-精氨酸进行肺灌注对 CPB 后肺损伤的保护作用。
新西兰白兔（n = 50，体重 2.5-2.8 千克）分为五组（每组 n = 10）：假手术组（仅开胸）、CPB 组（无肺灌注的 CPB）、灌注组（CPB 加肺灌注）、L-精氨酸组（CPB 加灌注+L-精氨酸）和 L-NAME 组（CPB 加灌注+L-NAME）。CPB 持续 60 分钟，然后再灌注 2 小时。CPB 期间，每 20 分钟通过肺动脉进行肺灌注。检查的参数包括：（1）肺血管阻力，（2）肺动脉内皮细胞松弛（器官腔研究），和（3）IR 标志物（髓过氧化物酶）和炎症标志物（TNF-α、IL-B、NF-κB）。
CPB 导致肺动脉内皮功能障碍，表现为肺血管阻力增加和肺动脉松弛受损。肺灌注可显著逆转该现象（P < 0.01），而与单独灌注相比，用 L-精氨酸作为 NO 前体与肺灌注一起，对肺动脉内皮细胞具有更显著的松弛能力（P < 0.05）。相应地，CPB 后肺实质髓过氧化物酶活性和炎症细胞因子水平也显著增加（P < 0.05）。肺灌注可部分减轻该反应，而额外的 L-精氨酸进一步减弱了炎症细胞因子的释放（P < 0.05）。
CPB 期间的肺灌注部分改善了 CPB 引起的肺损伤。用 L-精氨酸进行肺灌注可以通过恢复内皮功能和减少炎症反应来进一步减轻肺损伤。
