title: The effect of aprotinin on ischemia-reperfusion injury in an in situ normothermic ischemic lung model.
abstract: OBJECTIVE
  In the context of the physiopathology of damage due to ischemic preservation and reperfusion injury following preservation, we aimed to demonstrate the positive effects of the addition of aprotinin, a serine protease inhibitor, to low potassium dextran (LPD), used as a single-flush solution in normothermic ischemic animal models, on lung protection and the prevention of reperfusion injury.
  
  
  METHODS
  In the study, 21 New Zealand white rabbits were used as experimental subjects. The subjects were ventilated with the assistance of a manual mechanical ventilator at 30 breaths/min and 10 ml/kg tidal volume. Lung protection solution was supplied to the pulmonary artery via a catheter. After applying the solution, ischemia was carried out for 120 min. At the end of this period, reperfusion was carried out for 90 min. The subjects were divided into three groups of seven subjects each. In the control group, pulmonary perfusion solution was not employed, whereas in the second group LPD was employed, and in the third group LPD and aprotinin (LPD+A) were perfused. Blood gas analysis, bronchoalveolar lavage (BAL) fluid examination, tissue malondialdehyde (MDA) level analysis and morphological examinations were performed.
  
  
  RESULTS
  The LPD+A group showed the significantly highest levels of oxygenation at the 15th and 60th minutes of reperfusion (297+/-76.7 and 327+/-97.4 mmHg) in comparison to the LPD (157+/-20.6 and 170+/-53.6 mmHg) and control (64+/-8.4 and 59+/-7.2 mmHg) groups (P<0.001). The LPD+A group showed the significantly lowest levels of alveolar-arterial oxygen difference at the 60th minute of reperfusion (389+/-15 mmHg) in comparison to the LPD (478+/-19 mmHg) and control (542+/-23) groups (P<0.001). The BAL fluid neutrophil percentage was significantly lower in the LPD+A group (22+/-2.4%) compared to the LPD (31+/-6.1%) and control (38+/-2.4%) groups. MDA levels were significantly lower in the LPD+A group (119.8+/-5.3 nmol MDA/g) when compared to the LPD (145.06+/-9.5 nmol MDA/g) and control (147.3+/-3.9 nmol MDA/g) groups (P<0.05). Morphological examinations revealed pathological lesions and alveolar hemorrhaging in all samples, with the LPD+A group having statistically more significant levels than the LPD and control groups (P<0.005). The LPD+A group had a significantly lower percentage of pathological lesions and alveolar hemorrhage grade values than the LPD and control groups (P<0.005).
  
  
  CONCLUSIONS
  It was observed that the addition of aprotinin to LPD solution as a pulmonary flush solution in an in situ normothermic ischemic lung model prevents reperfusion injury by means of various mechanisms and also protects the morphological, functional and biochemical integrity of the lung. In our view, therefore, the addition of aprotinin to lung protection solution will provide positive results in lung transplantation protocols.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Dicle University School of Medicine, 21280 Diyarbakir, Turkey. sevval@dicle.edu.tr
authors.forename: Sevval
authors.initials: S
authors.lastname: Eren
authors.forename: Hidir
authors.initials: H
authors.lastname: Esme
authors.forename: Akin E
authors.initials: AE
authors.lastname: Balci
authors.forename: Omer
authors.initials: O
authors.lastname: Cakir
authors.forename: Huseyin
authors.initials: H
authors.lastname: Buyukbayram
authors.forename: M Nesimi
authors.initials: MN
authors.lastname: Eren
authors.forename: Levent
authors.initials: L
authors.lastname: Erdinc
authors.forename: Omer
authors.initials: O
authors.lastname: Satici
mesh_terms: D000818:Animals; D007611:Aprotinin / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015227:Lipid Peroxidation; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D023421:Models, Animal; D009504:Neutrophils / Q000276:immunology; D010100:Oxygen / Q000097:blood; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*
chemical_list: D015842:Serine Proteinase Inhibitors; D007611:Aprotinin; D010100:Oxygen