title: Mafenide (Sulfamylon) inhibits plasmin fibrinolytic activity.
abstract: Inflammatory fibrinolysis by plasmin or phagocyte proteases is a major cause of skin graft failure on burn wounds where the primary adherent attachment of the skin grafts is due to the glue-like action of fibrin. We investigated the potential of mafenide acetate solution, an experimental topical antimicrobial used in treating grafted burn wounds, to modify plasmin fibrinolytic activity in vitro and, thus, its potential to alter or modify the integrity of the fibrin glue critical for skin graft viability. Immobilized 125I-fibrin monolayers were used to assay fibrinolytic activity from plasmin or from plasma activated by streptokinase or urokinase and modified by the presence of mafenide or epsilon-aminocaproic acid (EACA). While streptokinase-activated plasma lysed 52.7 +/- 3.9% of the 125I-fibrin, this plasmin activity was more than 80% inhibitable by EACA. Mafenide acetate had no intrinsic fibrinolytic activity (1.5 +/- 0.3%) nor activated plasma fibrinolytic potential (2.4 +/- 0.5%), but produced significant and dose-related reduction in fibrinolytic activity (p less than 0.001). Other sulfonamide analogues lacking a para-methylamino reactive group had 10-100 fold less antifibrinolytic potency while lysine, like mafenide, able to compete for plasmin binding sites, could potently block fibrinolysis. Mafenide did not qualitatively alter activation of plasminogen or affect generation of complexes with alpha 2 antiplasmin complexes. Adding mafenide only minutes following streptokinase-activated plasma or plasmin with the fibrin substrate reduced antifibrinolytic activity, supporting the conclusion that mafenide, like EACA, can modulate the interaction between fibrin and the plasmin reactive sites and thus prevent close plasmin/fibrin apposition.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis.
authors.forename: D J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: J H
authors.initials: JH
authors.lastname: Aldridge
mesh_terms: D005341:Fibrinolysin / Q000037:antagonists & inhibitors*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008272:Mafenide / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D013449:Sulfonamides; D008272:Mafenide; D005341:Fibrinolysin