TY - JOUR
T1 - Neutrophil endopeptidase inhibitor improves pulmonary function during reperfusion after eighteen-hour preservation
AU - Binns, O. A.R.
AU - DeLima, N. F.
AU - Buchanan, S. A.
AU - Mauney, M. C.
AU - Cope, J. T.
AU - Thies, S. D.
AU - Shockey, K. S.
AU - Tribble, C. G.
AU - Kron, I. L.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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U2 - 10.1016/S0022-5223(96)70042-9
DO - 10.1016/S0022-5223(96)70042-9
M3 - Article
C2 - 8800146
AN - SCOPUS:0029859285
SN - 0022-5223
VL - 112
SP - 607
EP - 613
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 3
ER -