Ex Vivo Lung Perfusion with β-Nicotinamide Adenine Dinucleotide (NAD) Improves Ischemic Lung Function.

Ischemia-reperfusion injury compromises short- and long-term outcomes after lung transplantation. The scarce existing data on NAD suggest effects on hypoxia-induced vasoconstriction, on reactive oxygen species and on tampering inflammation. We exposed rat lungs to 14 h of cold ischemic storage and perfused them in a rat ex vivo lung perfusion (EVLP) system for 4 h. A control group ( = 6) was compared to groups receiving 100 µM ( = 6) or 200 µM NAD ( = 6) in the preservation solution and groups receiving 200 µM ( = 4) or 2000 µM ( = 6) NAD every 30 min in the perfusate, starting at 1 h of EVLP. Compared to the control, significant effects were only achieved in the 2000 µM NAD group. During the 4 h of EVLP, we monitored higher vascular flow, lower mean pulmonary arterial pressure and increased oxygenation capacity. Tissue inflammation estimated with the myeloperoxidase assay was lower in the 2000 µM NAD group. We observed higher levels of anti-inflammatory IL-10, higher anti-inflammatory IL-6/IL-10 ratios and lower levels of pro-inflammatory IL-12 and IL-18 as well as a trend of more anti-inflammatory IFNy in the 2000 µM NAD perfusate. In the bronchoalveolar lavage, the pro-inflammatory levels of IL-1α and IL-1β were lower in the 2000 µM NAD group. NAD administered during EVLP is a promising agent with both anti-inflammatory properties and the ability to improve ischemic lung function.