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

J Heart Lung Transplant. 2005 Oct;24(10):1673-9. doi: 10.1016/j.healun.2004.11.014.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Vasodilator Agents
  • Iloprost