L-arginine in lung graft preservation and reperfusion

Background: Inhaled nitric oxide has been shown to ameliorate early lung gr aft dysfunction. It improves oxygenation by inducing pulmonary vasodilatati on in well-ventilated lung areas, and it also modulates leukocyte-endotheli um interactions. We used a porcine, single lung transplantation model to ev aluate whether the benefits of exogenously administered gas could be achiev ed easier by adding L-arginine, the substrate of endogenous nitric oxide sy nthesis, as an additive to the flush solution and intravenously during repe rfusion. Methods: Six pig lungs were flushed with modified Euro-Collins solutions co ntaining L-arginine (2 g/liter). After cold (4 degrees C) storage, the left lung was transplanted. Ischemic time was 260 minutes. The recipients recei ved 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 vascul ar resistance (PVR) in the transplanted and in the native lung using a righ t heart bypass model. We measured blood gases, leukocyte counts, plasma fre e-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 transp lanted 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 bad no effect on oxygenation or carbo n dioxide exchange of the transplanted lung. Nor did L-arginine treatment h ave any effect on leukocyte sequestration or myeloperoxidase activity in th e 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.