Inhalative pre-treatment of donor lungs using the aerosolized prostacyclin analog iloprost ameliorates reperfusion injury.

Abstract

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.

• Authors: Thorsten Wittwer, Ulrich F W Franke, Matthias Ochs, Tim Sandhaus, Alex Schuette, Stefan Richter, Niels Dreyer, Lars Knudsen, Thomas Müller, Harald Schubert, Joachim Richter, 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. 24 Issue 10 Pg. 1673-9 (Oct 2005) ISSN: 1557-3117 [Electronic] United States
• PMID: 16210146 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Vasodilator Agents
• Iloprost

Topics

• Administration, Inhalation
• Animals
• Female
• Iloprost (administration & dosage)
• Lung Compliance (drug effects)
• Lung Diseases (physiopathology, prevention & control)
• Lung Transplantation
• Models, Animal
• Nebulizers and Vaporizers
• Organ Preservation
• Preoperative Care
• Pulmonary Edema (prevention & control)
• Reperfusion Injury (physiopathology, prevention & control)
• Swine
• Tissue Donors
• Vascular Resistance (drug effects)
• Vasodilator Agents (administration & dosage)