Summary
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 gluelike 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 ε-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 <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 α2 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. The
union of mafenide’s potent antimicrobial activity with its antifibrinolytic potential
is a fortuitous combination. The beneficial antifibrinolytic effect of mafenide may
control inflammatory proteolysis, promote skin graft retention, and support wound
healing.
Keywords
Fibrinolysis - Plasmin - Mafenide
