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

Research paper by Nikolaus N Pizanis, Vitaly V Milekhin, Konstantinos K Tsagakis, Ivan I Aleksic, Markus M Kamler, Heinz H Jakob

Indexed on: 08 May '07Published on: 08 May '07Published in: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery



Abstract

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.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 degrees C. Hemodynamics and blood gases were monitored until 6 h after reperfusion. Lung tissue was taken for wet/dry ratio assessment.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.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.

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