EFFECT OF HEXADIMETHRINE BROMIDE ON PLASMA KININ FORMATION, HYDROLYSIS OF P-TOSYL-L-ARGININE METHYL ESTER AND FIBRINOLYSIS.

The antiheparin agent hexadimethrine bromide, in concentrations of 20 to 200 mug/ml., inhibited the activation by active Hageman factor of the plasma enzyme which releases kinin from substrate. Once activated, this kinin-forming enzyme was not consistently inhibited by hexadimethrine in a concentration of 1 mg/ml. Surfaces which induce kinin formation by activating Hageman factor in plasma (glass, kaolin, celite, barium carbonate and carboxymethylcellulose) were inactivated by bathing in aqueous solutions of hexadimethrine. The effects of hexadimethrine on Hageman factor and on glass were not abolished by amounts of heparin which neutralize most other actions of hexadimethrine. Hexadimethrine prevented the activation by kaolin, but not by streptokinase, of p-tosyl-L-arginine methyl ester-splitting and fibrinolytic factors in plasma; once these enzymes were activated by kaolin, they could not be inhibited by hexadimethrine. Hexadimethrine, given locally or intravenously into guinea-pigs, reduced the increase in capillary permeability produced by intracutaneous injections of kaolin suspensions.