Additives improve lung function during EVLP
Recent studies suggest that inhalation of antioxidant N-acetylcysteine (NAC) or the addition of an adenosine receptor antagonist to the perfusate during Ex-Vivo Lung Perfusion (EVLP) can significantly reduce inflammation in the donor lung.
Yamada et al., 2017, (Zurich), subjected pig lungs to 24 hours of cold (4°C) storage followed by two hours of warm EVLP during which NAC was administered by nebulizer, whilst a control group received nebulized saline. After transplantation, and one hour of reperfusion, the lungs were isolated by occluding the right main bronchus and pulmonary artery. Changes in physiological response over the following five hours were recorded.
Unsurprisingly, the authors found that antioxidant therapy with NAC during EVLP reduced the overall inflammatory response (myeloperoxidase in EVLP perfusate and nuclear factor kB one hour after reperfusion.) The authors had previously shown the beneficial effects of N-acetylcysteine (NAC) on post-transplant lung function, when both donor and recipient were pre-treated intravenously.
Adenosine A2B receptor antagonist
In another porcine study reported from Charlottesville, USA, (Charles et al, 2017), lungs donated after circulatory /cardiac death (DCD lungs) were exposed to two hours of warm ischemia. The lungs were then subjected to four hours of cold preservation or to warm EVLP. ATL802, an adenosine A2B receptor antagonist, was administered to select groups, (to both cold preservation and warm EVLP groups) and the effects were then investigated on post-transplant outcomes.
Warm EVLP + ATL802 significantly improved dynamic lung compliance compared with EVLP alone and compared with cold preservation. However, no differences in oxygenation or pulmonary oedema were observed between EVLP and EVLP + ATL802, although there was a significant decrease in IL-12 expression in tissue and bronchoalveolar lavageto ATL802’s advantage.
In the latter half of 2017, several other groups reported positive effects of other additives to the EVLP perfusate. Among them, Cosgun T et al (also from Zurich) showed that ex-vivo administration of trimetazidine improves post-transplant lung function in the pig model. And from Toronto, Lin et al (2017), in a tough prolonged ischemia model (preserved at 4°C for 24 hours, and then subjected to normothermic EVLP for 12 hours) reported that alpha 1-Anti-trypsin improves the function of porcine donor lungs when added to the Steen solution perfusate during ex-vivo lung perfusion.
1. Yamada et al, Ex vivo treatment with inhaled N-acetylcysteine in porcine lung transplantation. J Surg Res. 2017 Oct;218:341-347 (link to abstract)
2. Charles et al, Lungs donated after circulatory death and prolonged warm ischemia are transplanted successfully after enhanced ex vivo lung perfusion using adenosine A2B receptor antagonism. J Thorac Cardiovasc Surg. 2017 Nov;154(5):1811-1820 (link to abstract)
3. Cosgun et al, Ex vivo administration of trimetazidine improves post-transplant lung function in pig model. Eur J Cardiothorac Surg. 2017 Jul 1;52(1):171-177 (link to abstract)
4. Lin et al, α1-Anti-trypsin improves function of porcine donor lungs during ex-vivo lung perfusion. J Heart Lung Transplant. 2017 Oct 2. pii: S1053-2498(17)32034-X (link to abstract)
Xvivo Insights PB-2018-01-28