ADDITION OF A MAST-CELL STABILIZING COMPOUND TO ORGAN PRESERVATION SOLUTIONS DEGREASES LUNG REPERFUSION INJURY

Objective: Research in lung transplant preservation has generally focu sed on free radicals and enzyme release from neutrophils, parenchymal cells, macrophages, and endothelium. The lung has a large resident pop ulation of mast cells that, when activated, release potent inflammator y mediators. We hypothesized that adding an inhibitor of mast cell deg ranulation, lodoxamide tromethamine (10 mu mol/L), to Euro-Collins and University of Wisconsin preservation solutions, would decrease lung p reservation 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% oxyge n. Alveolar-arterial oxygen difference, oxygen tension, capillary filt ration coefficient, and compliance were determined. Results: After 6 h ours of ischemic storage: lodoxamide tromethamine-enhanced Euro-Collin s solution decreased alveolar-arterial oxygen difference from 539 to 4 57 (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 s olution 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-e nhanced Euro-Collins solution decreased alveolar-arterial oxygen diffe rence from 588 to 485 (p < 0.001), increased oxygen tension from 100 t o 161 mm Hg (p = 0.012), decreased capillary filtration coefficient fr om 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 < 0.00 1), 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 i njury as demonstrated by increased oxygenation, decreased microvascula r permeability, and increased compliance. These results are relevant a s Euro-Collins and University of Wisconsin solutions are the most comm on clinically used lung preservation solutions. This study also highli ghts the deleterious role of resident mast cells in preservation injur y.