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Improvement of pulmonary microcirculation after lung transplantation using phosphodiesterase-5 inhibitor modified preservation solution

Department of Thoracic and Cardiovascular Surgery, West German Heart Center Essen, University Hospital of Essen, Hufelandstr. 55, 45122 Essen, Germany

Received 22 July 2008; received in revised form 26 December 2008; accepted 7 January 2009.

^_* Corresponding author. Tel.: +49 201 723 4901. (Email: Nikolaus.Pizanis{at}uni-essen.de).

Objective: Optimising the preservation modality and thus maintaining the post-transplanted organ function remains a point of interest in research in order to prevent deleterious ischaemia/reperfusion injury. Microcirculation allows the assessment of initial graft function before obvious functional parameters. It was the aim of our study to compare the effects of epoprostenol and sildenafil on the pulmonary microcirculation and haemodynamics, when used in the preservation solution in lung transplantation. Methods: Twenty-one pigs underwent single LuTx after 24 h graft-ischaemia, preserved with buffered low potassium-dextran solution (I, control); with addition of 0.66 µg/kg/bw epoprostenol (II) or with 0.15 mg/kg/bw sildenafil (III). The pulmonary microcirculation, alveolar capillary diameter (ACD), red blood cell (RBC) velocity and functional capillary density (FCD), were assessed by intravital microscopy (OPS-imaging) hourly until 6 h after reperfusion. Haemodynamics and blood gas exchange were monitored at all timepoints. Results: ACD was increased in group III directly after reperfusion (132 ± 4.4% vs 121 ± 3.1%, in % of baseline, III vs I; mean ± SEM; p < 0.05) and decreased during the experiment. RBC velocity did not reach statistical significance (256 ± 93 vs 263 ± 85 and 283 ± 66 µm/s, III vs II and I; mean ± SD). FCD in group III was higher than in I and II beginning 3 h after reperfusion (10.1 ± 1.4 vs 6.1 ± 1.9 µm/µm², III vs I; mean ± SEM; p < 0.05). Conclusions: Our study demonstrated a significantly improved microcirculation after application of PDF V during organ procurement, probably because of better distribution of the preservation solution. Further studies are necessary, to prove the long-term effects of this observation.

Key Words: Experimental lung transplantation • Organ preservation • Ischaemia/reperfusion injury • Phosphodiesterase-5 inhibitor