PDE-5 inhibitor donor intravenous preconditioning is superior to supplementation in standard preservation solution in experimental lung transplantation.
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 degrees 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.
Pizanis
Nikolaus
N
Department of Thoracic and Cardiovascular Surgery, West German Heart Center Essen, University Hospital of Essen, Germany. nikolaus.pizanis@uni-essen.de
Milekhin
Vitaly
V
Tsagakis
Konstantinos
K
Aleksic
Ivan
I
Kamler
Markus
M
Jakob
Heinz
H
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004353:Drug Evaluation, Preclinical; D015633:Extravascular Lung Water / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects; D016040:Lung Transplantation; D008297:Male; D009926:Organ Preservation / Q000379:methods; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000502:physiology; D011654:Pulmonary Edema / Q000473:pathology / Q000517:prevention & control; D011687:Purines / Q000494:pharmacology; D015427:Reperfusion Injury / Q000517:prevention & control; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine; D019172:Transplantation Conditioning / Q000379:methods*; D014655:Vascular Resistance / Q000187:drug effects
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5