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Eur J Cardiothorac Surg 2007;32:42-47. doi:10.1016/j.ejcts.2007.03.044
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

PDE-5 inhibitor donor intravenous preconditioning is superior to supplementation in standard preservation solution in experimental lung transplantation

Department of Thoracic and Cardiovascular Surgery, West German Heart Center Essen, University Hospital of Essen, Germany

Received 23 October 2006; received in revised form 26 March 2007; accepted 28 March 2007.

^_* Corresponding author. Address: Department of Thoracic and Cardiovascular Surgery, West German Heart Center Essen, University Hospital of Essen, Hufelandstr. 55, 45122 Essen, Germany. Tel.: +49 201 723 4901. (Email: nikolaus.pizanis{at}uni-essen.de).

Objective: Improvement of preservation is still a major research objective in lung transplantation. The effects of phosphodiesterase-5 (PDE-5) inhibitors during procurement are still not clear. It was the aim of this study to investigate the effect of sildenafil on post-transplanted lung function in a porcine model using different application procedures. Methods: In control group lungs were flushed with buffered low-potassium dextran (LPD) solution (I) and compared to LPD solution with supplementation of 0.15 mg/kg body weight (BW) sildenafil (II), whereas in a third group 0.15 mg/kg BW sildenafil was administered intravenously 20 min prior to LPD flushing (III). All grafts were stored for 24 h at 4–6 °C. Hemodynamics and blood gases were monitored until 6 h after reperfusion. Lung tissue was taken for wet/dry ratio assessment. Results: All animals of groups I and III survived the entire observation period in contrast to four animals of group II which died within 4 h after reperfusion due to severe reperfusion injury. Group II showed a lower mean PAP and a reduced pulmonary vascular resistance (PVR) throughout the observation period, but did not reach significance due to low number of surviving animals. Group III achieved significantly improved PO₂/FiO₂ fraction at all timepoints and a significant reduced PVR [434 ± 98 vs 594 ± 184 dyn s cm^–5, II vs I; mean ± SD, p < 0.01] at 6 h. Wet/dry ratio was significantly higher in group II throughout the experiment. Conclusions: Sildenafil allows for a better graft function after 24 h ischemia when given prior to standard flushing and preservation. This effect can be explained by a complete/homogenous preservation achieved by selective pulmonal vasodilatation. However, this effect seems to persist when sildenafil remains in the storage solution, leading to severe pulmonary edema.

Key Words: Ischemia/reperfusion injury • Lung transplantation • Lung preservation • Phosphodiesterase-5 inhibitor