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 T¹, Iskender I¹, Yamada Y¹, Arni S¹, Lipiski M²,van Tilburg K³, Weder W¹, Inci I¹. (Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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