Oar. Binns et al., NEUTROPHIL ENDOPEPTIDASE INHIBITOR IMPROVES PULMONARY-FUNCTION DURINGREPERFUSION AFTER 18-HOUR PRESERVATION, Journal of thoracic and cardiovascular surgery, 112(3), 1996, pp. 607-613
Background: Reperfusion injury remains a significant problem after lun
g transplantation and is thought to be in part mediated by neutrophils
. Ulinastatin inhibits release of elastase and cathepsin G from neutro
phil granules, We hypothesized that inhibition of these neutrophil end
opeptidases (proteases) would attenuate pulmonary reperfusion injury,
Methods: With an isolated, whole blood-perfused, ventilated rabbit lun
g model, we Studied the effects of ulinastatin. All lungs were flushed
with cold Euro-Collins solution, harvested en bloc, stored inflated a
t 4 degrees C for 18 hours, and reperfused with whole blood, The 18-ho
ur control lungs (n = 8) were stored and reperfused, Low-dose (n = 8)
and high-dose (n = 7) groups were treated with total doses of ulinasta
tin of 25,000 and 50,000 units, respectively, during flush and reperfu
sion. An additional control group of lungs (n = 8) was harvested, flus
hed, and immediately reperfused, Results: The pulmonary artery pressur
e was significantly lower in the high-dose group than in the 18-hour c
ontrol group (36.7 +/- 1.8 vs 44.8 +/- 2.9 mm Hg, p = 0.034), The perc
entage 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 ulinasta
tin treatments did not result in a significant improvement in oxygenat
ion 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 reperfusi
on injury after 18 hours of hypothermic pulmonary ischemia, with resul
tant improvements in pulmonary artery pressure and airway compliance,
Improvement in pulmonary function after preservation and reperfusion w
ith a neutrophil endopeptidase inhibitor confirms the role of endopept
idases in reperfusion injury and suggests an intervention to reduce th
eir detrimental effects on early graft function.