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Epinephrine exerts anticoagulant effects during human endotoxemia.

van der Poll T, Levi M, Dentener M, Jansen PM, Coyle SM, Braxton CC, Buurman WA, Hack CE, ten Cate JW, Lowry SF - J. Exp. Med. (1997)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Cornell University Medical College, Department of Surgery, New York 10021, USA.

ABSTRACT
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.

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Epinephrine inhibits LPS-induced coagulation activation.  Mean (± SE) plasma concentrations of prothrombin fragment F1+2 and  TAT complexes  after intravenous injection of LPS (2 ng/kg, lot EC-5) at  t = 0. LPS = subjects injected with LPS only (n = 6); EPI-3 = subjects  infused with epinephrine (30 ng/kg/min) from t = −3 h to 6 h (n = 5);  EPI-24 = subjects infused with epinephrine (30 ng/kg/min) from t =  −24 h to 6 h (n = 6). Both EPI-3 and EPI-24 attenuated LPS-induced  increases in F1+2 and TAT complexes (P <0.05 versus LPS only).
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Figure 1: Epinephrine inhibits LPS-induced coagulation activation. Mean (± SE) plasma concentrations of prothrombin fragment F1+2 and TAT complexes after intravenous injection of LPS (2 ng/kg, lot EC-5) at t = 0. LPS = subjects injected with LPS only (n = 6); EPI-3 = subjects infused with epinephrine (30 ng/kg/min) from t = −3 h to 6 h (n = 5); EPI-24 = subjects infused with epinephrine (30 ng/kg/min) from t = −24 h to 6 h (n = 6). Both EPI-3 and EPI-24 attenuated LPS-induced increases in F1+2 and TAT complexes (P <0.05 versus LPS only).

Mentions: Infusion of epinephrine only (day 1) did not influence the plasma concentrations of F1+2 or TAT complexes (data not shown). Injection of LPS induced transient rises in plasma F1+2 and TAT complexes, peaking after 4 h (4.61 ± 1.03 nmol/l and 31.9 ± 4.7 ng/ml, respectively; both P <0.05 versus time). Both EPI-3 and EPI-24 strongly attenuated LPS-induced coagulation activation (Fig. 1). In the EPI-3 group, peak concentrations of F1+2 and TAT complexes were 1.88 ± 0.34 nmol/l and 16.5 ± 5.6 ng/ml, respectively, in the EPI-24 group, 2.25 ± 0.55 nmol/l and 14.6 ± 4.4 ng/ml, respectively (all P <0.05 versus LPS only).


Epinephrine exerts anticoagulant effects during human endotoxemia.

van der Poll T, Levi M, Dentener M, Jansen PM, Coyle SM, Braxton CC, Buurman WA, Hack CE, ten Cate JW, Lowry SF - J. Exp. Med. (1997)

Epinephrine inhibits LPS-induced coagulation activation.  Mean (± SE) plasma concentrations of prothrombin fragment F1+2 and  TAT complexes  after intravenous injection of LPS (2 ng/kg, lot EC-5) at  t = 0. LPS = subjects injected with LPS only (n = 6); EPI-3 = subjects  infused with epinephrine (30 ng/kg/min) from t = −3 h to 6 h (n = 5);  EPI-24 = subjects infused with epinephrine (30 ng/kg/min) from t =  −24 h to 6 h (n = 6). Both EPI-3 and EPI-24 attenuated LPS-induced  increases in F1+2 and TAT complexes (P <0.05 versus LPS only).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196238&req=5

Figure 1: Epinephrine inhibits LPS-induced coagulation activation. Mean (± SE) plasma concentrations of prothrombin fragment F1+2 and TAT complexes after intravenous injection of LPS (2 ng/kg, lot EC-5) at t = 0. LPS = subjects injected with LPS only (n = 6); EPI-3 = subjects infused with epinephrine (30 ng/kg/min) from t = −3 h to 6 h (n = 5); EPI-24 = subjects infused with epinephrine (30 ng/kg/min) from t = −24 h to 6 h (n = 6). Both EPI-3 and EPI-24 attenuated LPS-induced increases in F1+2 and TAT complexes (P <0.05 versus LPS only).
Mentions: Infusion of epinephrine only (day 1) did not influence the plasma concentrations of F1+2 or TAT complexes (data not shown). Injection of LPS induced transient rises in plasma F1+2 and TAT complexes, peaking after 4 h (4.61 ± 1.03 nmol/l and 31.9 ± 4.7 ng/ml, respectively; both P <0.05 versus time). Both EPI-3 and EPI-24 strongly attenuated LPS-induced coagulation activation (Fig. 1). In the EPI-3 group, peak concentrations of F1+2 and TAT complexes were 1.88 ± 0.34 nmol/l and 16.5 ± 5.6 ng/ml, respectively, in the EPI-24 group, 2.25 ± 0.55 nmol/l and 14.6 ± 4.4 ng/ml, respectively (all P <0.05 versus LPS only).

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Cornell University Medical College, Department of Surgery, New York 10021, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus