Pulmonary perfusion with L-arginine ameliorates post-cardiopulmonary bypass lung injury in a rabbit model.
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.
Chao
Yin Kai
YK
Graduate Institute of Clinical Medical Sciences, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Wu
Yi Cheng
YC
Yang
Kun Ju
KJ
Chiang
Ling Ling
LL
Liu
Hui Ping
HP
Lin
Pyng Jing
PJ
Chu
Yen
Y
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
D053583:Interleukin-1beta; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D001120:Arginine; D009195:Peroxidase