A genetically engineered human Kunitz protease inhibitor with increased kallikrein inhibition in an ovine model of cardiopulmonary bypass

A recombinant human serine protease inhibitor known as Kunitz protease inhi bitor (KPI) wild type has functional similarities to the bovine Kunitz inhi bitor, aprotinin, and had shown a potential to reduce bleeding in an ovine model of cardiopulmonary bypass (CPB), The aim of this study was to assess KPI-185, a modification of KPI-wild type that differs from KPI-wild type in two amino acid residues and which enhances anti-kallikrein activity in a f urther double-blind, randomized study in an ovine model of CPB, and to comp are with our previous study of KPI-wild type and aprotinin in the same ovin e model. Post-operative drain losses and subjective assessment of wound 'dr yness' showed no significant differences between KPI-185 and KPI-wild type, despite the significant enhancement of kallikrein inhibition using KPI-185 seen in serial kallikrein inhibition assays. These preliminary findings support the hypothesis that kallikrein inhibitio n is not the major mechanism by which Kunitz inhibitors such as aprotinin r educe perioperative bleeding.