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 inhibitor (KPI) wild type has functional similarities to the bovine Kunitz inhibitor, 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 further double-blind, randomized study in an ovine model of CPB, and to compare with our previous study of KPI-wild type and aprotinin in the same ovine model. Post-operative drain losses and subjective assessment of wound 'dryness' 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.

Genetically engineered serine protease inhibitor for hemostasis after cardiac operations.

Background: The serine protease inhibitor aprotinin has been widely reported for its beneficial action in limiting blood loss after cardiopulmonary bypass (CPB). A potent human serine protease inhibitor known as protease nexin II or amyloid precursor protein has been recently isolated. A recombinant protein known as recombinant Kunitz protease inhibitor (rKPI; Scios Nova, Mountain View, CA) with sequence homology to the protease nexin II-amyloid precursor protein molecule has been manufactured.

The haemodynamic effects of the thromboxane A2 receptor antagonist GR32191B during cardiopulmonary bypass in the dog.

This study examined whether treatment with the specific thromboxane (TX) A2 receptor antagonist GR32191B would result in an improvement in peripheral haemodynamics during and after cardiopulmonary bypass (CPB) in anaesthetized dogs compared with animals given either saline (control) or aspirin. Following thoracotomy, heparinization and aortic cannulation, and 35 minutes before CPB, dogs received intravenously either GR32191B (15 micrograms/kg/min), saline (50 ml bolus) or aspirin (225 mg bolus) (n = 6 per group). Cardiac output (dye dilution), femoral artery blood flow (electromagnetic flowmeter), gastrocnemius muscle tissue perfusion (133Xe clearance), retinal blood flow (fluorescein angiography), and thromboxane biosynthesis (urinary excretion rates of TXB2 and the metabolite 2,3-dinor-TXB2) were measured before, during and after a standard 90 minute period of CPB at 2.

Effects of cardiopulmonary bypass on gut blood flow, oxygen utilization, and intramucosal pH.

Studies documenting rises in endotoxin after cardiopulmonary bypass (CPB) have postulated gut mucosal hypoperfusion. We have investigated alterations in jejunal blood flow by laser Doppler flow measurement, intramucosal pH (pHi) by tonometry, and oxygen utilization in a canine model of hypothermic CPB (n = 11 dogs). After 10 minutes of hypothermic CPB, despite no major reduction in superior mesenteric artery flow, mucosal laser Doppler flow decreased to -38.