Surfactant application in experimental lung transplantation.

Abstract

BACKGROUND:

Non-heart-beating donor (NHBD) utilization can significantly increase the limited donor lung pool. However, optimal preservation of organ function is crucial as the development of ischemia/reperfusion injury (IRI) can result in severe surfactant inactivation. Exogenic surfactant application is effective in prevention and therapy of IRI. Studies on optimal timing of Curosurf, including application in NHBDs, have not been done, but could help to optimize NHBD lung transplantation.

METHODS:

The extracorporeal screening model (ESM) included rat lungs (Sprague-Dawley, n = 5/group) preserved with Perfadex. In 3 test groups, Curosurf was administered before flush preservation (T1), after 4-hour ischemia (T2) or during reperfusion (T3). Results after extracorporeal reperfusion were compared with controls. The transplantation model (TM) consisted of asystolic pigs (n = 5/group) ventilated for 7 hours with warm ischemia (WIT, Groups 1 and 2). In Group 2, 100 mg/kg BW Curosurf was bronchoscopically administered before preservation. After 3-hour cold storage, left lung transplantation was performed and data were compared with sham control data (Group 3).

RESULTS:

For the ESM, T1 lung oxygenation (SurfT1 167±47.4 mm Hg) was superior to others (SurfT2 47.3±15.3 mm Hg, SurfT3 77.2±48.8 mm Hg, controls 65.5±46.2 mm Hg; p<0.02). Stereology demonstrated poorer intra-alveolar edema formation in controls (1.86±2.53% of parenchyma) compared with surfactant-treated lungs (<0.02% of parenchyma) (p<0.02). Intra-alveolar erythrocyte sequestration as an indicator of vascular leakage was significantly lower in T1 lungs (0.15±0.12% of parenchyma) compared with all other groups (>0.74% of parenchyma). For TM, mortality was 80% in the untreated group and 100% in the Curosurf group, suggesting that a 7-hour WIT is above the limit for NHBD utilization.

CONCLUSIONS:

Donor lung pre-treatment with endobronchial pre-preservation Curosurf offers optimal preservation quality when compared with post-ischemic application or during reperfusion and results in improved functional outcome when compared with controls. Expensive NHBD pre-treatment with Curosurf cannot improve poor allograft outcome after extended WIT and should therefore not be considered. Seven-hour WIT seems generally to be above the limits for use in NHBD lung donors.

• Authors: Thorsten Wittwer, Navid Madershahian, Parwis Rahmanian, Yeong-Hoon Choi, Klaus Neef, Konrad Frank, Jochen Müller-Ehmsen, Matthias Ochs, Christian Mühlfeld, Thorsten Wahlers
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 32 Issue 3 Pg. 355-9 (Mar 2013) ISSN: 1557-3117 [Electronic] United States
• PMID: 23313558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biological Products
• Phospholipids
• Pulmonary Surfactants
• poractant alfa

Topics

• Animals
• Biological Products (therapeutic use)
• Female
• In Vitro Techniques
• Lung Transplantation
• Male
• Organ Preservation (methods)
• Phospholipids (therapeutic use)
• Pulmonary Surfactants (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Sus scrofa