appears to have an effect on vessel permeability which allows the migration of leukocytes through the blood vessel into the perivascular region the effect of protein c on capillary leakage in guinea pigs was studied in order to confirm the efficacy of protein c in antagonizing enhanced vessel permeability in anesthetized guinea pigs the study was carried out as follows after intravenous administration of evan 39 s blue anesthetized guinea pigs received either a protein c concentrate or a formulation buffer thereafter the test animals were treated with histamine or thrombin intracutaneously to induce enhanced vessel permeability or with saline as a control the animals were then examined visually for the occurrence of discoloration of the resulting wheals the results are depicted in fig4 histamine treatment protein c or saline fig5 thrombin treatment protein c or saline and fig6 thrombin treatment buffer or saline in these studies a colorless wheal was recorded as a negative observation i e no disturbance in permeability whereas a blue skin coloration at the injection site was defined as a positive observation i e increased vessel permeability the percentage of positive wheals among total wheals produced by the same substance and does within each group of treated animals n 12 per treatment group was calculated the results in fig4 plot the percent positive blue colored wheals after intracutaneous injection of varying amounts of histamine shown on the y axis u2218 and ue8a0 represent the effects of i v administered saline n 12 and i v administration of 800 iu protein c kg body weight n 12 respectively the results in fig5 plot the percent positive wheals after intracutaneous injection of varying amounts of thrombin shown on the x axis u25a1.