Hemodynamic and proteolytic effects of intravenous injection of purified human plasma kallikrein

Abstract

To investigate the precise hemodynamic effects of purified human plasma kallikrein, small doses (0.3 U/kg) of this proteolytic enzyme were infused over 10 s in five pigs. Hemodynamic performance was evaluated by means of a Swan-Ganz catheter, and parameters of the plasma kallikrein-kinin, coagulation, and fibrinolytic systems were determined by means of chromogenic peptide substrate assays. The infusions of plasma kallikrein were followed by rapid decreases in mean arterial pressure (to 43 +/- 2% of baseline values) and increases in cardiac output (to 145 +/- 6% of baseline values), accounting for marked decreases in systemic vascular resistance, to 28 +/- 1% of initial values. Heart rate, mean pulmonary arterial, central venous, and pulmonary capillary wedge pressures did not change after the injection. Pulmonary vascular resistance decreased to 69 +/- 3% of baseline values. The hemodynamic changes gradually normalized during the following 10 min. Functional levels of prekallikrein, kallikrein, kallikrein inhibition, prothrombin, antithrombin III, plasmin, and antiplasmin were not affected by the injection or the resulting hemodynamic changes; the hematocrit and the number of circulating leukocytes or platelets were also unaffected.

Kallikrein Activates Prothrombin

“…Figure 1 demonstrates that 10 μg/mL kallikrein, that is about 25% of the normal plasmatic concentration of prekallikrein, generates about 15 mIU/mL K allikrein is a very important enzyme in coagulation, fibrinolysis, inflammation, and cell growth [1][2][3][4][5][6][7][8][9][10][11][12][13] ; kallikrein activates the contact phase enzymes of coagulation, kallikrein converts the important fibrinolysis proenzyme single-chain urokinse into the active enzyme urokinase, 14 kallikrein amplificates inflammation, and kallikrein affects cell growth. This study was undertaken to determine whether this interesting enzyme with so many substrates also directly activates prothrombin to thrombin, the most important enzyme of hemostasis.…”

Oxygen Radicals Induce Pulmonary Vasoconstriction in Pigs without Activating Plasma Proteolytic Cascade Systems

“…These activities were considered to be of negligible effect on the pulmonary hemodynamics and the bio chemical measurements in the doses applied [22,24], Analysis Plasma kallikrein activity, prekallikrein and func tional kallikrein inhibition values from the left atrium were determined with chromogenic peptide substrate S-2302 (Kabi, Stockholm. Sweden) using an auto mated enzyme analyzer (Cobas Bio, Hoffmann-La Roche, Basel.…”

“…When activated, the contact factors plasma prekallikrein, Hageman factor (FXII) and fac tor XI are converted to serine proteases that are capable of activating the plasma comple ment, fibrinolytic, coagulation and the kallikrein-kinin systems [1][2][3][4][5], Activation of the proteolytic cascade systems of plasma is asso ciated with trauma, septicemia, adult respira tory distress syndrome as well as the neonatal respiratory distress syndrome [6][7][8][9][10][11][12][13][14], Pre-studies [20][21][22][23][24], Increased concentration of thromboxane At was also found in pulmonary venous plasma when the pulmonary circula tion was exposed to oxygen radical generating systems and this could explain the pulmonary vasoconstriction found in such experiments [15,18,19], In addition it is well known that endotoxincmia activates the plasma proteo lytic systems [6,8,9], Both oxygen radicals and endotoxins increase capillary permeabil ity and induce edema. Therefore, from a theo retical point of view, several possible linkages between plasma proteolytic systems as the plasma kallikrein-kinin and fibrinolytic sys tems and oxygen radicals may exist.…”