3. Ex vivo administration of trimetazidine improves post-transplant lung function in pig model


Eur J Cardiothorac Surg. 2017 Jul 1;52(1):171-177. doi: 10.1093/ejcts/ezx053.

Cosgun T1Iskender I1Yamada Y1Arni S1Lipiski M2,van Tilburg K3Weder W1Inci I1. (Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.



Ex vivo lung perfusion (EVLP) is not only used to assess marginal donor lungs but is also used as a platform to deliver therapeutic agents outside the body. We previously showed the beneficial effects of trimetazidine (TMZ) on ischaemia reperfusion (IR) injury in a rat model. This study evaluated the effects of TMZ in a pig EVLP transplant model.


Pig lungs were retrieved and stored for 24 h at 4°C, followed by 4 h of EVLP. Allografts were randomly allocated to 2 groups ( n  = 5 each). TMZ (5 mg/kg) was added to the prime solution prior to EVLP. After EVLP, left lungs were transplanted and recipients were observed for 4 h. Allograft gas exchange function and lung mechanics were recorded hourly throughout reperfusion. Microscopic lung injury and inflammatory and biochemical parameters were assessed.


There was a trend towards better oxygenation during EVLP in the TMZ group ( P  = 0.06). After transplantation, pulmonary gas exchange was significantly better during the 4-h reperfusion period and after isolation of the allografts for 10 min ( P  < 0.05). Tissue thiobarbituric acid levels, myeloperoxidase activity and protein concentrations in bronchoalveolar lavage samples were significantly lower in the TMZ group at the end of EVLP ( P  < 0.05).


Ex vivo treatment of donor lungs with TMZ significantly improved immediate post-transplant lung function. Further studies are warranted to understand the effect of this strategy on long-term lung function. 

KEYWORDS: Ex vivo lung perfusion; Ischaemia reperfusion injury; Lung transplantation; Trimetazidine. PMID: 28874022 DOI:10.1093/ejcts/ezx053