PREVENTION OF MICROVASCULAR THROMBOSIS WITH SHORT-TERM INFUSION OF HUMAN TISSUE-TYPE PLASMINOGEN-ACTIVATOR

A locally active thrombolytic agent, human tissue-type plasminogen act ivator (t-PA), given over a finite time period (24 hours) by local inf usion, maintains long-term microvascular patency (7 days) in a proven thrombosis model using an arterial inversion graft in the rabbit model . Thirteen rabbits in the control group and 16 rabbits in the experime ntal group underwent an arterial inversion graft followed by continuou s infusion (24 hours) with human tissue-type plasminogen activator (ex perimental) or normal saline (control). No significant clinical bleedi ng or alteration of coagulation parameters was noted in hematologic st udies in both experimental and control groups. Scanning electron micro scopy of the postoperative human tissue-type plasminogen activator-per fused arteries suggests an interaction of the human tissue-type plasmi nogen activator with specific platelet receptors in reversing microvas cular thrombosis by decreasing or preventing further platelet aggregat ion and adhesion. Human tissue-type plasminogen activator infused loca lly for a finite period (24 hours) allows adequate time for platelet m etamorphosis to occur in converting a thrombogenic to a nonthrombogeni c vessel surface. The clinical ramifications in preventing or reversin g microvascular thrombosis in free-tissue transfers and replantation s urgery are apparent. Further study in this area will enhance our under standing of the pathogenesis and prevention of microvascular thrombosi s.