ADDITION OF APROTININ TO ORGAN PRESERVATION SOLUTIONS DECREASES LUNG REPERFUSION INJURY

Background. Organ preservation injury is associated with endothelial c ell damage, destabilization of mitochondrial and cell membranes, and t he release of proteolytic enzymes. In addition to its well-known clini cal effect of reducing perioperative blood loss, aprotinin has antipro teolytic and membrane-stabilizing properties. We hypothesized that add ing aprotinin to Euro-Collins (EC) and University of Wisconsin (UW) so lutions would decrease preservation injury in cultured endothelial cel ls and a whole organ rat lung model. Methods. Bovine aortic endothelia l cells were cultured and stored in the respective solution at 4 degre es C for 12 or 48 hours. Endothelial cell viability after storage was assessed by dimethylthiazole tetrazolium cytotoxicity assay. In the wh ole organ model, rat lungs were isolated, flushed with the respective solution, and stored at 4 degrees C for 6 or 12 hours. The lungs were ventilated with 100% O-2 and reperfused with fresh blood. Alveolar-art erial O-2 difference, O-2 tension, capillary filtration coefficient, a nd compliance were determined. Results. Endothelial cell viability was optimized with the addition of aprotinin to EC and UW at a dose of 15 0 KIU/mL (0.02 mg/mL). In the isolated perfused lung model, after 6 ho urs of ischemic storage, aprotinin-enhanced (100 KIU/mL [0.014 mg/mL]) EC and UW decreased alveolar-arterial O-2 difference, increased O-2 t ension, and decreased capillary filtration coefficient compared with E C and UW alone. After 12 hours of ischemic storage, aprotinin-enhanced EC and UW decreased alveolar-arterial O-2 difference, increased O-2 t ension, decreased capillary filtration coefficient, and increased comp liance compared with EC and UW alone. Conclusions. The addition of apr otinin to EC and UW solutions increases endothelial cell viability in hypoxic cold storage conditions. In terms of whole organ function, apr otinin improves lung preservation as demonstrated by increased oxygena tion and compliance, and decreased capillary permeability. This study is clinically applicable as there is already extensive experience with the use of aprotinin in heart and lung transplant recipients, in addi tion to its routine use in conventional cardiac operations. (Ann Thora c Surg 1998;66:225-30). (C) 1998 by The Society of Thoracic Surgeons.