title: C1-esterase inhibitor reduces reperfusion injury after lung transplantation.
abstract: BACKGROUND
  Activation of the complement system and polymorphonuclear neutrophilic leukocytes plays a major role in mediating reperfusion injury after lung transplantation. We hypothesized that early interference with complement activation would reduce lung reperfusion injury after transplantation.
  
  
  METHODS
  Unilateral left lung autotransplantation was performed in 6 sheep. After hilar stripping the left lung was flushed with Euro-Collins solution and preserved for 2 hours in situ at 15 degrees C. After reperfusion the right main bronchus and pulmonary artery were occluded, leaving the animal dependent on the reperfused lung (reperfused group). C1-esterase inhibitor group animals (n = 6) received 200 U/kg body weight of C1-esterase inhibitor as a short infusion, half 10 minutes before, the other half 10 minutes after reperfusion. Controls (n = 6) underwent hilar preparation only. Pulmonary function was assessed by alveolar-arterial oxygen difference and pulmonary vascular resistance. The release of beta-N-acetylglucosaminidase served as indicator of polymorphonuclear neutrophilic leukocyte activation. Extravascular lung water was an indicator for pulmonary edema formation. Biopsy specimens were taken from all groups 3 hours after reperfusion for light and electron microscopy.
  
  
  RESULTS
  In the reperfused group, alveolar-arterial oxygen difference and pulmonary vascular resistance were significantly elevated after reperfusion. All animals developed frank alveolar edema. The biochemical marker beta-N-acetylglucosaminidase showed significant leukocyte activation. In the C1-esterase inhibitor group, alveolar-arterial oxygen difference, pulmonary vascular resistance, and the level of polymorphonuclear neutrophilic leukocyte activation were significantly lower.
  
  
  CONCLUSIONS
  Treatment with C1-esterase inhibitor reduces reperfusion injury and improves pulmonary function in this experimental model.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, J.W. Goethe University, Frankfurt/Main, Germany. m.scherer@em.uni-frankfurt.de
authors.forename: Mirela
authors.initials: M
authors.lastname: Scherer
authors.forename: Stefanos
authors.initials: S
authors.lastname: Demertzis
authors.forename: Frank
authors.initials: F
authors.lastname: Langer
authors.forename: Anton
authors.initials: A
authors.lastname: Moritz
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Schäfers
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000502:physiology; D003174:Complement C1 Inactivator Proteins / Q000627:therapeutic use*; D005260:Female; D006982:Hypertonic Solutions; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008168:Lung / Q000502:physiology; D016040:Lung Transplantation / Q000009:adverse effects / Q000502:physiology; D023421:Models, Animal; D019188:Organ Preservation Solutions; D010100:Oxygen / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D012756:Sheep; D014655:Vascular Resistance
chemical_list: D003174:Complement C1 Inactivator Proteins; C037096:Euro-Collins' solution; D006982:Hypertonic Solutions; D019188:Organ Preservation Solutions; D010100:Oxygen