title: Endobronchial donor pre-treatment with ventavis: is a second administration during reperfusion beneficial to optimize post-ischemic function of non-heart beating donor lungs?
abstract: BACKGROUND
  Lung retrieval from non-heart-beating donors (NHBD) has been introduced into clinical practice successfully. However, because of potentially deleterious effects of warm ischemia on microvascular integrity, use of NHBD lungs is limited by short tolerable time periods before preservation. Recently, improvement of NHBD graft function was demonstrated by donor pre-treatment using aerosolized Ventavis (Schering Inc., Berlin, Germany). Currently, there is no information whether additional application of this approach in reperfusion can further optimize immediate graft function.
  
  
  METHODS
  Asystolic pigs (n = 5/group) were ventilated for 180-min of warm ischemia (groups 1-3). In groups 2 and 3, 100 microg Ventavis were aerosolized over 30-min using an ultrasonic nebulizer (Optineb). Lungs were then retrogradely preserved with Perfadex and stored for 3-h. After left lung transplantation and contralateral lung exclusion, grafts were reperfused for 6-h. Only in group 3, another dose of 100 microg Ventavis was aerosolized during the first 30-min of reperfusion. Hemodynamics, pO2/FiO2 and dynamic compliance were monitored continuously and compared to controls. Intraalveolar edema was quantified stereologically, and extravascular-lung-water-index (EVLWI) was measured. Statistics comprised ANOVA analysis with repeated measurements.
  
  
  RESULTS
  Dynamic compliance was significantly lower in both Ventavis groups, but additional administration did not result in further improvement. Oxygenation, pulmonary hemodynamics, EVLWI and intraalveolar edema formation were comparable between groups.
  
  
  CONCLUSIONS
  Alveolar deposition of Ventavis in NHBD lungs before preservation significantly improves dynamic lung compliance and represents an important strategy for improvement of preservation quality and expansion of warm ischemic intervals. However, additional application of this method in early reperfusion is of no benefit.
authors.affiliation: Department of Cardiothoracic Surgery, University Hospital of Cologne, Cologne, Germany. Th.Wittwer-MD@t-online.de
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wittwer
authors.forename: Ulrich F W
authors.initials: UF
authors.lastname: Franke
authors.forename: Tim
authors.initials: T
authors.lastname: Sandhaus
authors.forename: Jan
authors.initials: J
authors.lastname: Groetzner
authors.forename: Justus T
authors.initials: JT
authors.lastname: Strauch
authors.forename: Jens
authors.initials: J
authors.lastname: Wippermann
authors.forename: Matthias
authors.initials: M
authors.lastname: Ochs
authors.forename: Christian
authors.initials: C
authors.lastname: Mühlfeld
authors.forename: Angelika
authors.initials: A
authors.lastname: Börner
authors.forename: Sibylle
authors.initials: S
authors.lastname: Streck
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wahlers
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D019332:Endothelin-1 / Q000097:blood; D015633:Extravascular Lung Water / Q000187:drug effects; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006323:Heart Arrest; D016285:Iloprost / Q000494:pharmacology*; D008170:Lung Compliance / Q000187:drug effects; D016040:Lung Transplantation; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control; D034421:Sus scrofa; D019172:Transplantation Conditioning / Q000379:methods*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D019332:Endothelin-1; D014665:Vasodilator Agents; D016285:Iloprost