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 hemostatic mechanism during endotoxemia, 17 healthy men were studied after intravenous injection of lipopolysaccharide (LPS, 2 ng/kg), while receiving 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 normal saline (n = 6). Activation of the coagulation system (plasma concentrations of thrombin-antithrombin III complexes and prothrombin fragment F1+2) was significantly attenuated in the groups treated with epinephrine when compared with subjects injected with LPS only (P <0.05). Epinephrine enhanced LPS-induced activation of fibrinolysis (plasma levels of tissue-type plasminogen activator and plasmin-alpha2-antiplasmin complexes; P <0.05), but did not influence inhibition of fibrinolysis (plasminogen activator inhibitor type I). In subjects infused with epinephrine, the ratio of maximal activation of coagulation and maximal activation of fibrinolysis was reduced by >50%. Hence, epinephrine exerts antithrombotic effects during endotoxemia by concurrent inhibition of coagulation, and stimulation of fibrinolysis. Epinephrine, whether endogenously produced or administered as a component of treatment, may limit the development of disseminated intravascular coagulation during systemic infection.
van der Poll
T
T
Cornell University Medical College, Department of Surgery, New York 10021, USA.
Levi
M
M
Dentener
M
M
Jansen
P M
PM
Coyle
S M
SM
Braxton
C C
CC
Buurman
W A
WA
Hack
C E
CE
ten Cate
J W
JW
Lowry
S F
SF
D000328:Adult; D000925:Anticoagulants; D001777:Blood Coagulation / Q000187:drug effects*; D019446:Endotoxemia / Q000097:blood*; D004837:Epinephrine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004926:Escherichia coli; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006487:Hemostasis; D006801:Humans; D007262:Infusions, Intravenous; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D000925:Anticoagulants; D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D004837:Epinephrine