L-Arginine in lung graft preservation and reperfusion.
BACKGROUND
Inhaled nitric oxide has been shown to ameliorate early lung graft dysfunction. It improves oxygenation by inducing pulmonary vasodilatation in well-ventilated lung areas, and it also modulates leukocyte-endothelium interactions. We used a porcine, single lung transplantation model to evaluate whether the benefits of exogenously administered gas could be achieved easier by adding L-arginine, the substrate of endogenous nitric oxide synthesis, as an additive to the flush solution and intravenously during reperfusion.


METHODS
Six pig lungs were flushed with modified Euro-Collins solutions containing L-arginine (2 g/liter). After cold (4 degrees C) storage, the left lung was transplanted. Ischemic time was 260 minutes. The recipients received intravenous boluses of L-arginine (30 mg/kg), followed by infusion (20 mg/kg/min) during the first 30 minutes of reperfusion. Six control animals received saline as placebo. We measured the blood flow and pulmonary vascular resistance (PVR) in the transplanted and in the native lung using a right heart bypass model. We measured blood gases, leukocyte counts, plasma free-radical trapping capacity, and diene conjugates in pulmonary venous blood and myeloperoxidase activity of the lung tissue.


RESULTS
Pulmonary vascular resistance was 4 to 5-fold higher in the transplanted lung than in the native lung, which received 80% of the total blood flow. L-arginine reduced PVR by 30% in the native lung (p < 0.001), but not in the transplanted lung. L-arginine had no effect on oxygenation or carbon dioxide exchange of the transplanted lung. Nor did L-arginine treatment have any effect on leukocyte sequestration or myeloperoxidase activity in the transplanted lung. The plasma antioxidant capacity in venous blood of the transplanted lung almost doubled shortly during early reperfusion without influence of L-arginine.


CONCLUSIONS
L-arginine reduced PVR in the native lung but did not improve pulmonary hemodynamics, gas exchange, or reduce leukocyte sequestration of the transplanted lung.
Vainikka
T
T
Department of Cardiothoracic Surgery, Helsinki University Central Hospital, Helsinki, Finland. tiina.vainikka@hus.fi
Heikkilä
L
L
Kukkonen
S
S
Toivonen
H J
HJ
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D005609:Free Radicals / Q000097:blood; D007958:Leukocyte Count; D008168:Lung / Q000098:blood supply / Q000187:drug effects; D016040:Lung Transplantation; D023421:Models, Animal; D009926:Organ Preservation; D009195:Peroxidase / Q000378:metabolism; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D015424:Reperfusion; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D005609:Free Radicals; D001120:Arginine; D009195:Peroxidase