Nitric oxide ventilation of rat lungs from non-heart-beating donors improves posttransplant function.
Lungs from non-heart-beating donors (NHBDs) would enhance the donor pool. Ex vivo perfusion and ventilation of NHBD lungs allows functional assessment and treatment. Ventilation of rat NHBD lungs with nitric oxide (NO) during ischemia, ex vivo perfusion and after transplant reduced ischemia-reperfusion injury (IRI) and improved lung function posttransplant. One hour after death, Sprague-Dawley rats were ventilated for another hour with either 60% O2 or 60% O2/40 ppm NO. Lungs were then flushed with 20-mL cold Perfadex, stored cold for 1 h, perfused in an ex vivo circuit with Steen solution and warmed to 37 degrees C, ventilated 15 min, perfusion-cooled to 20 degrees C, then flushed with cold Perfadex and stored cold. The left lung was transplanted and ventilated separately. Recipients were sacrificed after 1 h. NO-ventilation was associated with significantly reduced wet:dry weight ratio in the ex vivo circuit, better oxygenation, reduced pulmonary vascular resistance, increased lung tissue levels of cGMP, maintained endothelial NOS eNOS, and reduced increases in tumor necrosis factor alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS). NO-ventilation had no effect on MAP kinases or NF-kappaB activation. NO administration to NHBDs before and after lung retrieval may improve function of lungs from NHBDs.
Division of Cardiothoracic Surgery, Department of Surgery, University of North Carolina at Chapel Hill, NC, USA.
B M
BM
Dong
J B
JB
Abano
T M
TM
Egan
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D016040:Lung Transplantation; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009926:Organ Preservation; D011654:Pulmonary Edema / Q000517:prevention & control; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*; D014019:Tissue Donors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D020928:Mitogen-Activated Protein Kinases; D006152:Cyclic GMP