Double-blinded, placebo-controlled study of early XXXX treatment in @entity1707 uncontrolled @entity548 model.

@entity1 @entity1707 @entity548 @entity190 @entity928 @entity927 @entity551 @entity130
BACKGROUND: @entity927 ( @entity928 ) is an antifibrinolytic drug that was shown to increase survival in @entity130 @entity1 , but the mechanisms remain unclear. The purpose of this double-blinded, randomized placebo-controlled study was to determine if @entity928 with @entity551 resuscitation with Hextend (HEX) or fresh frozen plasma (FFP) reduced @entity190 ( @entity190 ) and improved survival in a model of uncontrolled @entity548 . METHODS: Instrumented, anesthetized @entity1707 (n = 11 per group) were subjected to 24-mL/kg controlled @entity548 , followed by transection of the spleen. After 15 minutes of bleeding, @entity928 (1.43 mg/kg/min) or normal saline (NS) was given over 10 minutes, and then 15-mL/kg HEX or FFP was administered. At 90 minutes, a second infusion of @entity928 or NS was given. @entity190 , coagulation status, and 5-hour survival were determined. Tissue plasminogen activator (tPA) was added to blood samples collected before and after @entity928 administration to confirm that the @entity928 inhibited fibrinolysis. In addition, a comparison of a dose response to tPA-induced fibrinolysis was made between @entity1707 and @entity1 plasma in vitro. RESULTS: @entity928 prevented the rise in d-dimers that occurred after @entity130 . However, there was no significant effect of @entity928 on survival or @entity190 compared with NS with HEX (HEX + NS, 17    2 mL/kg vs. HEX + @entity928 , 17    2 mL/kg) or FFP (FFP + NS, 7    2 mL/kg vs. FFP + @entity928 , 12    3 mL/kg), while FFP significantly reduced @entity190 and increased survival compared with HEX in the NS-treated animals. The tPA-induced fibrinolysis was inhibited in the blood from @entity928 -treated animals, yet in fibrinolysis sensitivity studies, @entity1 plasma was 30 times more sensitive to tPA-induced fibrinolysis than @entity1707 plasma. CONCLUSION: @entity928 did not reduce @entity190 , even though @entity928 was antifibrinolytic in the @entity1707 . The possibility remains that the @entity1707 is highly resistant to fibrinolysis and not a good model to study the effects of antifibrinolytics or that fibrinolysis is not a major factor in bleeding from @entity130 .
