RECOMBINANT KUNITZ PROTEASE INHIBITOR AMELIORATES REPERFUSION INJURY IN RAT LUNG TRANSPLANTATION

Background. Recombinant Kunitz protease inhibitor (rKPI-BG022) is more homologous to human Kunitz protease inhibitor than is aprotinin. Beca use aprotinin has been reported to inhibit free radicals, we hypothesi zed that rKPI would ameliorate reperfusion injury caused by free radic als. We examined its effect and the timing of administration in an in vivo rat lung transplantation model. Methods. All lungs were flushed w ith law-potassium dextran-1% glucose solution and stored for 24 hours at 4 degrees C, then orthotopic left lung transplantations were perfor med. Rats were divided into 4 groups (n = 6) as follows: group 1 serve d as control; in Group 2, rKPI was added to the flush solution (10 mu mol/L); in group 3, rKPI (5 mg/kg) was administered intravenously to t he recipient just after reperfusion; and in group 4, rKPI was added to the flush solution (10 mu mol/L) and rKPI (5 mg/kg) was administered intravenously to the recipient just after reperfusion. Twenty-four hou rs after transplantation, the right main pulmonary artery and right ma in bronchus were ligated, and the rats were ventilated with 100% O-2 f or 5 minutes. Peak airway pressure, blood gas analysis, serum lipid pe roxide level, tissue myeloperoxidase activity, and wet-dry weight rati o were measured. Results. The partial oxygen tension values of group 2 were higher than those of groups 1 and 4 (groups 1, 2, and 4: 104.8 /- 15.8, 245.1 +/- 49.0, 101.4 +/- 4.5 mm tig, respectively; p < 0.01) . The partial carbon dioxide tension values of groups 3 and 4 were low er than those of group 1 (groups 1, 3, and 4: 74.5 +/- 5.7, 42.0 +/- 1 1.0, 46.0 +/- 8.4 mm Hg, respectively; p < 0.05). Peak airway pressure s were lower in groups 2 and 3 than in groups I and 4 (groups 1, 2, 3, and 4: 22.5 +/- 0.5, 18.2 +/- 0.5, 19.2 +/- 0.8, 22.5 +/- 1.1 mm Hg; p < 0.01). Serum lipid peroxide levels in groups 2 and 3 were lower th an those of groups 1 and 4 (groups 1, 2, 3, and 4: 0.793 +/- 0.037, 0. 577 +/- 0.069, 0.560 +/- 0.029, and 0.785 +/- 0.053 nmol/mL, respectiv ely; groups 2 and 3 vs group I, and group 3 vs group 4: p < 0.01; grou p 2 vs group 4: p < 0.05). There were no differences in wet-dry weight ratio and tissue myeloperoxidase activity between the groups. Conclus ion. Recombinant Kunitz protease inhibitor ameliorates reperfusion inj ury caused by free radicals in an in vivo rat lung transplantation mod el. Administration of rKPI through the flush solution and intravenous injection after reperfusion were effective separately, but the combina tion of the two administrations was not effective. (C) 1998 by The Soc iety of Thoracic Surgeons.