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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

Nikolaus Pizanis*, Vitaly Milekhin, Konstantinos Tsagakis, Ivan Aleksic, Markus Kamler, Heinz Jakob

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




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Copyright © 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier. All rights reserved.