Immunohistochemical Study of Thrombolytic Mechanisms.

I N PREVIOUS REPORTS1-3 various methods, including radiotracer studies, revealed the capacity of plasmin to adsorb selectively to preformed venous and arterial clots. Components of the fibrinolysin system were labeled with iodine131 and their distribution studied following intravenous administration. The highest degree of adsorption to fibrin clots was exhibited by human plasminogen activated with streptokinase ( SK ) or urokinase ( UK ) . Spontaneously activated human plasmin or chloroform-activated bovine plasmin exhibited less localizing capacity. The inactive precursor plasminogen also localized in clots to some extent. On the other hand, plasminogen activators as UK and SK given alone behaved as the radio-iodinated albumin control. Both experimentally and clinically,1’4#{176} clot lysis following plasmin infusion was found to proceed long after the disappearance of any measurable circulating fibrinolytic activity. Radioactivity measurement revealed the presence of a plasmin-antiplasmin complex which seems to release free plasmin to the fibin substrate. The studies with I’31-labeled plasmin preparations involve two sources of error. First, since even the purest plasmin preparations available at present contain various protein impurities, the danger exists that part of the 1131.. labeled material which was found to localize in fibrin clots actually represented impurities rather than plasmin itself. Second, it was shown1 that radioiodination alters enzymatic activities to some extent and what was measured actually was the distribution of partially denatured enzymes. For this reason it was decided to repeat these experiments using immunotiuorescent technics.