title: Addition of a mast cell stabilizing compound to organ preservation solutions decreases lung reperfusion injury.
abstract: OBJECTIVE
  Research in lung transplant preservation has generally focused on free radicals and enzyme release from neutrophils, parenchymal cells, macrophages, and endothelium. The lung has a large resident population of mast cells that, when activated, release potent inflammatory mediators. We hypothesized that adding an inhibitor of mast cell degranulation, lodoxamide tromethamine (10 micromol/L), to Euro-Collins and University of Wisconsin preservation solutions, would decrease lung preservation injury.
  
  
  METHODS
  Rat lungs were isolated, flushed with the respective solution, and stored at 4 degrees C for 6 or 12 hours. The lungs were reperfused with fresh blood and ventilated with 100% oxygen. Alveolar-arterial oxygen difference, oxygen tension, capillary filtration coefficient, and compliance were determined.
  
  
  RESULTS
  After 6 hours of ischemic storage: lodoxamide tromethamine-enhanced Euro-Collins solution decreased alveolar-arterial oxygen difference from 539 to 457 (p = 0.004), increased oxygen tension from 119 to 205 mm Hg (p = 0.006), and decreased capillary filtration coefficient from 3.9 to 2.0 (p < 0.001); lodoxamide tromethamine-enhanced University of Wisconsin solution decreased alveolar-arterial oxygen difference from 546 to 317 (p < 0.001), increased oxygen tension from 166 to 335 mm Hg (p < 0.001), and decreased capillary filtration coefficient from 3.0 to 1.7 (p < 0.001). After 12 hours of ischemic storage, lodoxamide tromethamine-enhanced Euro-Collins solution decreased alveolar-arterial oxygen difference from 588 to 485 (p < 0.001), increased oxygen tension from 100 to 161 mm Hg (p = 0.012), decreased capillary filtration coefficient from 6.2 to 2.6 (p < 0.001), and increased compliance from 0.12 to 0.21 (p < 0.001); lodoxamide tromethamine-enhanced University of Wisconsin solution decreased alveolar-arterial oxygen difference from 478 to 322 (p < 0.001), increased oxygen tension from 214 to 335 mm Hg (p < 0.001), decreased capillary filtration constant from 4.2 to 2.0 (p < 0.001), and increased compliance from 0.20 to 0.25 (p < 0.001).
  
  
  CONCLUSIONS
  Addition of lodoxamide tromethamine to Euro-Collins or University of Wisconsin solution results in a marked decrease in lung reperfusion injury as demonstrated by increased oxygenation, decreased microvascular permeability, and increased compliance. These results are relevant as Euro-Collins and University of Wisconsin solutions are the most common clinically used lung preservation solutions. This study also highlights the deleterious role of resident mast cells in preservation injury.
authors.affiliation: Department of Surgery, University of Southern California School of Medicine, Los Angeles 90033, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Barr
authors.forename: J N
authors.initials: JN
authors.lastname: Carey
authors.forename: G P
authors.initials: GP
authors.lastname: Nishanian
authors.forename: R F
authors.initials: RF
authors.lastname: Roberts
authors.forename: Y
authors.initials: Y
authors.lastname: Sakamaki
authors.forename: S H
authors.initials: SH
authors.lastname: Darbinian
authors.forename: V A
authors.initials: VA
authors.lastname: Starnes
mesh_terms: D000818:Animals; D000975:Antioxidants; D006982:Hypertonic Solutions; D066298:In Vitro Techniques; D008168:Lung / Q000502:physiology; D008297:Male; D008407:Mast Cells; D009570:Nitriles; D019188:Organ Preservation Solutions; D010072:Oxamic Acid / Q000031:analogs & derivatives*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D014325:Tromethamine / Q000031:analogs & derivatives*
chemical_list: D000975:Antioxidants; C037096:Euro-Collins' solution; D006982:Hypertonic Solutions; D009570:Nitriles; D019188:Organ Preservation Solutions; D014325:Tromethamine; C022028:lodoxamide tromethamine; D010072:Oxamic Acid