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

Abstract

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.

Effects of ulinastatin (urinary trypsin inhibitor) on ATP, intracellular pH, and intracellular sodium transients during ischemia and reperfusion in the rat kidney in vivo

“…Moreover, oxygen free radicals produced during reperfusion after ischemia may contribute to the destruction of cellular membranes. UTI has been reported to have a protective effect against renal ischemia by the stabilization of the lysosomal membrane, the inhibition of lysosomal enzymes such as elastase and catepsin G [5,6], and its action as a free radical scavenger [6,18], but there have been no reports from the in vivo metabolic point of view. In this study, pHi, ATP, and Nai levels were restored faster in the UTI group than in the NS group after reperfusion under the same MAP.…”

“…Ulinastatin (UTI; urinary trypsin inhibitor) is a Kunitz-type protease inhibitor that inhibits the activity or release of lysosomal enzymes such as elastase and catepsin G [5,6]. It has been reported to help protect against shock and operative stress [7-10] and suppress the deterioration of renal function associated with surgical procedures, chemotherapy, and various types of shock [11][12][13].…”

Neutrophil Elastase Inhibitor Ameliorates Reperfusion Injury in a Canine Model of Lung Transplantation

“…Naka et al [18] showed that local complement was activated during the hypothermic preservation period and that neutrophils stimulated by this complement injured endothelial cells in the acute phase directly after reperfusion. Binns et al [19] showed that neutrophil endopeptidase inhibitor improved pulmonary function at 30 min of reperfusion after 18 h of cold preservation.…”

Urinary Trypsin Inhibitor, an Alternative Therapeutic Option for Inflammatory Disorders

“…Also, UTI can alleviate coagulatory disturbance accompanied by sepsis such as an increase in the serum level of fibrinogen and fibrinogen degradation products [33]. Likewise, UTI has a protective effect against ischemiareperfusion injury in the liver [35], kidney [36], heart [37], and lung [38] in vivo via the actions of its radical scavenging elements [39]. As for its mechanism, UTI reduces C-X-C chemotactic molecule production during liver ischemia/reperfusion in vivo [40].…”