Induction of endogenous fibrinolysis inhibition in the dog. Effect of intravascular coagulation and release of free fatty acids.
Possible mechanisms underlying the development of fibrinolysis inhibition following trauma were studied. In order to investigate the role of intravascular coagulation dogs were subjected to infusions of thrombin or endotoxin, which both caused an increase in urokinase inhibitor activity in serum after 24 and 48 hours. The inhibitor increase following thrombin infusion was not, however, prevented by previous defibrinogenation with Defibrase or by induction of thrombocytopenia with antiplatelet serum, suggesting that neither platelets nor fibrinogen are necessary for the post-traumatic occurrence of fibrinolysis inhibition. In all groups subjected to infusion of thrombin an increase in plasma free fatty acids (FFA) was observed. The role of this increase for the development of fibrinolysis inhibition was tested by infusion of norepinephrine alone and in combination with nicotinic acid. Norepinephrine caused an increase of FFA after 2 hours and in urokinase inhibitor activity after 24-48 hours. Both of these were diminished by high doses of nicotinic acid, indicating that the release of FFA rather than intravascular coagulation might be the principal mechanism underlying the occurrence of fibrinolysis inhibition following trauma.
D000818:Animals; D012103:Batroxobin / Q000494:pharmacology; D001792:Blood Platelets / Q000276:immunology; D004285:Dogs; D004731:Endotoxins / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D007106:Immune Sera / Q000494:pharmacology; D008297:Male; D009539:Nicotinic Acids / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*; D013921:Thrombocytopenia / Q000097:blood; D014148:Tranexamic Acid / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000097:blood
D004731:Endotoxins; D005230:Fatty Acids, Nonesterified; D007106:Immune Sera; D009539:Nicotinic Acids; D014148:Tranexamic Acid; D012103:Batroxobin; D013917:Thrombin; D014568:Urokinase-Type Plasminogen Activator; D009638:Norepinephrine