title: Pulmonary perfusion with L-arginine ameliorates post-cardiopulmonary bypass lung injury in a rabbit model.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Yin Kai
authors.initials: YK
authors.lastname: Chao
authors.forename: Yi Cheng
authors.initials: YC
authors.lastname: Wu
authors.forename: Kun Ju
authors.initials: KJ
authors.lastname: Yang
authors.forename: Ling Ling
authors.initials: LL
authors.lastname: Chiang
authors.forename: Hui Ping
authors.initials: HP
authors.lastname: Liu
authors.forename: Pyng Jing
authors.initials: PJ
authors.lastname: Lin
authors.forename: Yen
authors.initials: Y
authors.lastname: Chu
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D010477:Perfusion; D009195:Peroxidase / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D001120:Arginine; D009195:Peroxidase