LOW-DOSE SODIUM-NITROPRUSSIDE REDUCES PULMONARY REPERFUSION INJURY

Background. Reperfusion injury is a significant cause of early allogra ft dysfunction after lung transplantation. We hypothesized that direct pulmonary arterial infusion of an intravascular nitric oxide donor, s odium nitroprusside (SNP), would ameliorate pulmonary reperfusion inju ry more effectively than inhaled nitric oxide without causing profound systemic hypotension. Methods. Using an isolated, ventilated, whole-b lood-perfused rabbit lung model, we studied the effects of both inhale d and intravascular nitric oxide during lung reperfusion. Group I (con trol) lungs (New Zealand White rabbits, 3 to 3.5 kg) were harvested en bloc, flushed with Euro-Collins solution, and then stored inflated fo r 18 hours at 4 degrees C. Lungs were then reperfused with whole blood and ventilated with 60% oxygen for 30 minutes. Groups II, III, and IV received pulmonary arterial infusions of SNP at 0.2, 1.0, and 5.0 mu g . kg(-1) . min(-1), respectively, whereas group V was ventilated wit h 60% oxygen and nitric oxide al 80 ppm during reperfusion. Results. P ulmonary arterial infusions of SNP even at 0.2 mu g . kg(-1) . min(-1) (group II) showed significant improvements in pulmonary artery pressu re (31.35 +/- 0.8 versus 40.37 +/- 3.3 mm Hg; p < 0.05) and pulmonary vascular resistance (38,946 +/- 1,269 versus 52,727 +/- 3,421 dynes . s/cm(-5); p < 0.05) when compared with control (group I) lungs after 3 0 minutes of reperfusion. Infusions of SNP at 1.0 mu g . kg(-1) . min( -1) (group III) showed additional significant improvements in dynamic airway compliance (1.98 +/- 0.10 versus 1.46 +/- 0.02 mL/mm Hg; p < 0. 05), venous-arterial oxygenation gradient (116.00 +/- 24.4 versus 34.4 3 +/- 2.5 mm Hg; p < 0.05), and wet-to-dry ratio (6.9 +/- 0.9 versus 9 .1 +/- 2.2; p < 0.05) when compared with control (group I) lungs, Lung s that received inhaled nitric oxide at 80 ppm (group V) were signific antly more compliant (1.82 +/- 0.13 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05) than control (group I) lungs. Conclusions. Pulmonary arterial i nfusion of low-dose SNP during lung reperfusion significantly improves pulmonary hemodynamics, oxygenation, compliance, and edema formation. These effects were achieved at doses of SNP that did not cause profou nd systemic hypotension. Direct intravascular infusion of SNP via pulm onary arterial catheters could potentially abate reperfusion injury im mediately after allograft implantation. (C) 1997 by The Society of Tho racic Surgeons.