Inhalative pre-treatment of donor lungs using the aerosolized prostacyclin analog iloprost ameliorates reperfusion injury.
BACKGROUND
Lung transplantation is effective for end-stage pulmonary disease, but its successful application is still limited by organ shortage and sub-optimal preservation techniques. Therefore, optimal allograft protection is essential to reduce organ dysfunction, especially in the early post-operative period. Intravenous prostanoids are routinely used to ameliorate reperfusion injury. However, the latest evidence suggests similar efficacy using inhaled prostacyclin. Thus, we evaluated the impact of donor pre-treatment using the prostacyclin analog, iloprost, on post-ischemic function of Perfadex-protected allografts.


METHODS
In Group 1, 5 pig lungs were preserved with Perfadex (PER group) solution and stored for 27 hours. In Group 2, 100 microg of iloprost was aerosolized over 30 minutes using a novel mobile ultrasonic nebulizer (Optineb) before identical organ harvest (PER-ILO group). After left lung transplantation and contralateral lung exclusion, hemodynamic variables, Po2/Fio2 and dynamic compliance were monitored for 6 hours and compared with sham-operated controls. Pulmonary edema was determined stereologically and by wet-to-dry (W/D) weight ratio. Statistical assessment included analysis of variance (ANOVA) with repeated measures.


RESULTS
Dynamic compliance and pulmonary vascular resistance (PVR) were superior in iloprost-treated compared with untreated organs (p < 0.05), whereas oxygenation was comparable between groups. W/D ratio revealed a significantly smaller amount of lung water in PER-ILO organs (p = 0.048), whereas stereologic data showed a trend toward less intra-alveolar edema.


CONCLUSIONS
Endobronchial application of iloprost in donor lungs before Perfadex preservation decreases post-ischemic edema and significantly improves lung compliance and vascular resistance. This innovative approach is easily applicable in the clinical setting and offers a new strategy for improvement of pulmonary allograft preservation.
Wittwer
Thorsten
T
Department of Cardiothoracic and Vascular Surgery, Friedrich-Schiller University, Jena, Germany. th.wittwer-md@t-online.de
Franke
Ulrich F W
UF
Ochs
Matthias
M
Sandhaus
Tim
T
Schuette
Alex
A
Richter
Stefan
S
Dreyer
Niels
N
Knudsen
Lars
L
Müller
Thomas
T
Schubert
Harald
H
Richter
Joachim
J
Wahlers
Thorsten
T
D000280:Administration, Inhalation; D000818:Animals; D005260:Female; D016285:Iloprost / Q000008:administration & dosage*; D008170:Lung Compliance / Q000187:drug effects; D008171:Lung Diseases / Q000503:physiopathology / Q000517:prevention & control*; D016040:Lung Transplantation; D023421:Models, Animal; D009330:Nebulizers and Vaporizers; D009926:Organ Preservation; D011300:Preoperative Care; D011654:Pulmonary Edema / Q000517:prevention & control; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine; D014019:Tissue Donors; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014665:Vasodilator Agents; D016285:Iloprost