Neutrophil endopeptidase inhibitor improves pulmonary function during reperfusion after eighteen-hour preservation

O. A.R. Binns, N. F. DeLima, S. A. Buchanan, M. C. Mauney, J. T. Cope, S. D. Thies, K. S. Shockey, C. G. Tribble, I. L. Kron

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background: Reperfusion injury remains a significant problem after lung transplantation and is thought to be in part mediated by neutrophils. Ulinastatin inhibits release of elastase and cathepsin G from neutrophil granules. We hypothesized that inhibition of these neutrophil endopeptidases (proteases) would attenuate pulmonary reperfusion injury. Methods: With an isolated, whole blood-perfused, ventilated rabbit lung model, we studied the effects of ulinastatin. All lungs were flushed with cold Euro-Collins solution, harvested en bloc, stored inflated at 4°C for 18 hours, and reperfused with whole blood. The 18-hour control lungs (n = 8) were stored and reperfused. Low-dose (n = 8) and high-dose (n = 7) groups were treated with total doses of ulinastatin of 25,000 and 50,000 units, respectively, during flush and reperfusion. An additional control group of lungs (n = 8) was harvested, flushed, and immediately reperfused. Results: The pulmonary artery pressure was significantly lower in the high-dose group than in the 18-hour control group (36.7 ± 1.8 vs 44.8 ± 2.9 mm Hg, p = 0.034). The percentage decrease in dynamic airway compliance was significantly less in the high-dose group than in the 18-hour control group (-13.8% ± 4.4% vs - 25.1% ± 3.7%, p = 0.032). Both low-dose and high-dose ulinastatin treatments did not result in a significant improvement in oxygenation with respect to the 18-hour control group (72.2 ± 25.8 vs 32.5 ± 4.9 mm Hg, p = 0.21). Conclusions: Ulinastatin diminishes reperfusion injury after 18 hours of hypothermic pulmonary ischemia, with resultant improvements in pulmonary artery pressure and airway compliance. Improvement in pulmonary function after preservation and reperfusion with a neutrophil endopeptidase inhibitor confirms the role of endopeptidases in reperfusion injury and suggests an intervention to reduce their detrimental effects on early graft function.

Original languageEnglish (US)
Pages (from-to)607-613
Number of pages7
JournalJournal of Thoracic and Cardiovascular Surgery
Volume112
Issue number3
DOIs
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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