A new preservation solution for lung transplantation: evaluation in a porcine transplantation model.

BACKGROUND: Lung preservation injury is still a major problem in lung transplantation. The aim of the current study was to evaluate the effects of a new preservation solution (Custodiol-N) for lung preservation. METHODS: Using an in vivo pig model, 7 lungs each were preserved for 24 hours after perfusion with: low-potassium dextran (LPD) solution as control (Group I); base solution of Custodiol-N without iron chelators (Group II); Custodiol-N (Group III); or Custodiol-N supplemented with dextran 40 (Group IV). Four animals received a sham operation. After left lung transplantation and contralateral lung exclusion, hemodynamics and blood gases were monitored for 6 hours; tissue samples were taken at the end of the experiments. RESULTS: All animals survived the transplantation procedure. Base solution- and Custodiol-N-preserved lungs (Groups II and III) showed graft function similar to that of LPD-preserved lungs (Group I), showing a trend toward improved values. Custodiol-N with dextran (Group IV) led to a significant reduction of mean pulmonary arterial pressure (20 ± 2 vs 28 ± 3 mm Hg, p < 0.01) and pulmonary vascular resistance (410 ± 51 vs 588 ± 83 dyne/s/cm(5), p < 0.01), and oxygenation ratio was significantly higher (536 ± 52 vs 313 ± 107 mm Hg at 6 hours, p < 0.01) and PCO(2) values were significantly lower (51 ± 9 vs 77 ± 5 mm Hg at 6 hours, p < 0.01) at 6 hours compared with LPD (Group I). Custodiol-N (Groups II to IV) showed a trend toward a lower wet/dry ratio and reduced oxidative stress; in the presence of dextran (Group IV), the difference was again statistically significant, when compared with LPD (Group I). CONCLUSIONS: Custodiol-N solution is a new alternative preservation solution for lung transplantation that offers significantly superior protection compared with LPD when dextran 40 is added.

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

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 24h graft-ischaemia, preserved with buffered low potassium-dextran solution (I, control); with addition of 0.66 microg/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 6h 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 microm/s, III vs II and I; mean+/-SD). FCD in group III was higher than in I and II beginning 3h after reperfusion (10.1+/-1.4 vs 6.1+/-1.9 microm/microm(2), 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.

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.