Monitoring of endogenous nitric oxide exhaled by pig lungs during ex-vivo lung perfusion

Abstract

In the context of organ shortage for transplantation, new criteria for better organ evaluation should be investigated. Ex-vivo lung perfusion (EVLP) allows extra-corporal lung re-conditioning and evaluation, under controlled parameters of the organ reperfusion and mechanical ventilation. This work reports on the interest of exhaled gas analysis during the EVLP procedure. After a 1 h cold ischemia, the endogenous gas production by an isolated lung of nitric oxide and carbon monoxide is simultaneously monitored in real time. The exhaled gas is analysed with two very sensitive and selective laser spectrometers developed upon the technique of optical-feedback cavity-enhanced absorption spectroscopy. Exhaled gas concentration measured for an ex-vivo lung is compared to the corresponding production by the whole living pig, measured before euthanasia. On-line measurements of the fraction of nitric oxide in exhaled gas (F_ENO) in isolated lungs are reported here for the first time, allowing to resolve the respiratory cycles. In this study, performed on 9 animals, F_ENO by isolated lungs range from 3.3 to 10.6 ppb with a median value of 4.4 ppb. Pairing ex-vivo lung and pig measurements allows to demonstrate a systematic increase of F_ENO in the ex-vivo lung as compared to the living animal, by a factor of 3 ± 1.2. Measurements of the fraction of carbon monoxide in exhaled gas (F_ECO) confirm levels recorded during previous studies driven to evaluate F_ECO as a potential marker of ischemia reperfusion injuries. F_ECO production by ex-vivo lungs ranges from 0.31 to 2.3 ppm with a median value of 0.8 ppm. As expected, these F_ECO values are lower than the production by the corresponding whole pig body, by a factor of 6.9 ± 2.7.

Keywords: carbon monoxide; ex-vivo lung perfusion; exhaled gas analysis; ischemia reperfusion injury; laser spectroscopy; lung graft evaluation; nitric oxide.