EPINEPHRINE EXERTS ANTICOAGULANT EFFECTS DURING HUMAN ENDOTOXEMIA

To determine the effect of a physiologically relevant elevation in the plasma concentrations of epinephrine on the activation of the hemosta tic mechanism during endotoxemia, 17 healthy men were studied after in travenous injection of lipopolysaccharide (LPS, 2 ng/kg), while receiv ing a continuous infusion of epinephrine (30 ng/kg/min) started either 3 h (n = 5) or 24 h (n = 6) before LPS injection, or an infusion of n ormal saline (n = 6). Activation of the coagulation system (plasma con centrations of thrombin-antithrombin III complexes and prothrombin fra gment F1+2) was significantly attenuated in the soups treated with epi nephrine when compared with subjects injected with LPS only (P<0.05). Epinephrine enhanced LPS-induced activation of fibrinolysis (plasma le vels of tissue-type plasminogen activator and plasmin-alpha(2)-antipla smin complexes; P<0.05), but did not influence inhibition of fibrinoly sis (plasminogen activator inhibitor type I). In subjects infused with epinephrine, the ratio of maximal activation of coagulation and maxim al activation of fibrinolysis was reduced by >50%. Hence, epinephrine exerts antithrombotic effects during endotoxemia by concurrent inhibit ion of coagulation, and stimulation of fibrinolysis. Epinephrine, whet her endogenously produced or administered as a component of treatment, may limit the development of disseminated intravascular coagulation d uring systemic infection.