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.
Pizanis
Nikolaus
N
Department of Thoracic and Cardiovascular Surgery, West German Heart Center Essen, University Hospital of Essen, Essen, Germany. Nikolaus.Pizanis@uni-essen.de
Heckmann
Jens
J
Wendt
Daniel
D
Tsagakis
Konstantinos
K
Jakob
Heinz
H
Kamler
Markus
M
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D011464:Epoprostenol / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000098:blood supply*; D016040:Lung Transplantation / Q000379:methods* / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009926:Organ Preservation / Q000379:methods; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000098:blood supply; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011687:Purines / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology; D034421:Sus scrofa; D016896:Treatment Outcome
D019188:Organ Preservation Solutions; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D011464:Epoprostenol