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

Abstract

Background: We investigated the effects of neutrophil elastase inhibitor ONO-5046 Na on lung ischemia-reperfusion injury in a canine model of single lung transplantation. Methods: 24 mongrel dogs, 12 donors and 12 recipients, were used for single lung transplantation. Lung grafts were preserved for 18 h by cold ischemia then transplanted into the left thoracic cavity of recipients. In 6 recipients (ONO group), a bolus of ONO-5046 Na (10 mg/kg) was introduced before reperfusion and followed by continuous infusion (10 mg/kg/h). The remaining 6 recipients (control group) did not receive ONO-5046 Na and thus served as controls. We evaluated lung function and respiratory parameters over 240 min. Results: The total cell number in bronchoalveolar lavage fluid increased significantly in the control group in comparison to that in the ONO group. Histologic scores after 4 h of reperfusion and myeloperoxidase activity were significantly lower in the ONO group than in the control group. Conclusion: Neutrophil elastase inhibitor ONO-5046 Na may be useful in ameliorating lung reperfusion injury after transplantation.

Effect of a 120 km endurance race on plasma and muscular neutrophil elastase and myeloperoxidase concentrations in horses

“…Elastase is able to digest elastin and other extracellular compounds (Shapiro 2002) and may also promote the extravasation of the neutrophils through the endothelial barrier (Scholz et al 2003). This enzyme plays also a role in the ischaemia-reperfusion injury (Bzeizi et al 1996;Okajima et al 2004;Aoki et al 2005). Interestingly, inhibition of ELT attenuates MPO activity in post ischaemic skeletal muscles suggesting a cooperation of ELT and MPO in muscle injuries (Carden and Korthuis 1996).…”

Effect of intensive exercise on plasmatic neutrophil elastase level in eventing and endurance horses

“…It may also take part in the activation process of MMP-9 (Ferry et al 1997). Higher levels of NE were found in the bronchoalveolar lavage fluid of horses with recurrent airway obstruction (Brazil et al 2005), in the plasma of horses suffering from intestinal pathologies (De la Rebière de Pouyade et al 2009b) and in ischaemia-reperfusion injuries (Okajima et al 2004;Aoki et al 2005). Consequently, elastase seems to take part in the pathological response of neutrophils during the inflammatory process.…”

“…NE released by activated neutrophils is recognised as an inflammatory and prognostic marker in various conditions (Gross et al 1993;Zorn et al 2003;Braga et al 2006;Langhorst et al 2008) and is implicated in inflammatory tissue damage (Jochum et al 1994;Ginsburg 1999). This enzyme also plays a role in ischaemia-reperfusion injuries (Bzeizi et al 1996;Okajima et al 2004;Aoki et al 2005;De la Rebière de Pouyade et al 2009b).…”

Cyclosporine Does Not Prevent Microvascular Loss in Transplantation but Can Synergize With a Neutrophil Elastase Inhibitor, Elafin, to Maintain Graft Perfusion During Acute Rejection

“…Neutrophils have long been known to be associated with the injury to transplanted lungs (9). It has also been shown that neutrophil accumulation in airway walls and in the bronchoalveolar lavage (BAL) fluid may increase the risk of developing obliterative bronchiolitis (OB) (10, 11).…”