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Prothrombotic response to norepinephrine infusion, mimicking norepinephrine stress-reactivity effects, is partly mediated by α-adrenergic mechanisms


von Känel, Roland; Heimgartner, Nadja; Stutz, Monika; Zuccarella-Hackl, Claudia; Hänsel, Alexander; Ehlert, Ulrike; Wirtz, Petra H (2018). Prothrombotic response to norepinephrine infusion, mimicking norepinephrine stress-reactivity effects, is partly mediated by α-adrenergic mechanisms. Psychoneuroendocrinology:Epub ahead of print.

Abstract

BACKGROUND: Stress-induced prothrombotic changes are mediated by the sympathetic nervous system and critically involved in mental triggering of acute coronary syndromes, but the underlying psychobiology is not fully understood. We tested the hypothesis that a norepinephrine (NE) infusion to mimic effects of stress-induced NE release on blood coagulation elicits prothrombotic changes and examined to what extent these would be mediated by an alpha-adrenergic mechanism.
METHODS AND RESULTS: In a single-blind placebo-controlled within-subjects design, 24 middle-aged, non-smoking, non-obese and normotensive men participated in three experimental trials with an interval between one and two weeks. Each trial applied two sequential infusions of 1 and 15 min duration with varying substances [i.e., saline as placebo, the non-specific α-blocker phentolamine (2.5 mg/min), and NE (5 μg/min)]: trial 1=saline + saline; trial 2=saline + NE, and trial 3=phentolamine + NE. Plasma levels of clotting factor VIII activity (FVIII:C), fibrinogen, and D-dimer were assessed from blood samples collected immediately before and 1 min and 20 min after infusion procedures. Compared to saline + saline, saline + NE induced increases over time in FVIII:C, fibrinogen, and D-dimer levels. With phentolamine + NE, fibrinogen levels remained increased compared to saline + saline, but changes in FVIII:C and D-dimer levels were no more different. Coagulation changes did not differ between saline + NE and phentolamine + NE.
CONCLUSIONS: NE infusion activates blood coagulation. The resulting prothrombotic state could be one psychobiological mechanism underlying mental triggering of acute coronary syndromes. Blockade of α-adrenergic receptors partly attenuated NE effects on coagulation and could be implied to have preventive potential in susceptible individuals.

Abstract

BACKGROUND: Stress-induced prothrombotic changes are mediated by the sympathetic nervous system and critically involved in mental triggering of acute coronary syndromes, but the underlying psychobiology is not fully understood. We tested the hypothesis that a norepinephrine (NE) infusion to mimic effects of stress-induced NE release on blood coagulation elicits prothrombotic changes and examined to what extent these would be mediated by an alpha-adrenergic mechanism.
METHODS AND RESULTS: In a single-blind placebo-controlled within-subjects design, 24 middle-aged, non-smoking, non-obese and normotensive men participated in three experimental trials with an interval between one and two weeks. Each trial applied two sequential infusions of 1 and 15 min duration with varying substances [i.e., saline as placebo, the non-specific α-blocker phentolamine (2.5 mg/min), and NE (5 μg/min)]: trial 1=saline + saline; trial 2=saline + NE, and trial 3=phentolamine + NE. Plasma levels of clotting factor VIII activity (FVIII:C), fibrinogen, and D-dimer were assessed from blood samples collected immediately before and 1 min and 20 min after infusion procedures. Compared to saline + saline, saline + NE induced increases over time in FVIII:C, fibrinogen, and D-dimer levels. With phentolamine + NE, fibrinogen levels remained increased compared to saline + saline, but changes in FVIII:C and D-dimer levels were no more different. Coagulation changes did not differ between saline + NE and phentolamine + NE.
CONCLUSIONS: NE infusion activates blood coagulation. The resulting prothrombotic state could be one psychobiological mechanism underlying mental triggering of acute coronary syndromes. Blockade of α-adrenergic receptors partly attenuated NE effects on coagulation and could be implied to have preventive potential in susceptible individuals.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
04 Faculty of Medicine > University Hospital Zurich > Klinik für Konsiliarpsychiatrie und Psychosomatik
06 Faculty of Arts > Institute of Psychology
Dewey Decimal Classification:150 Psychology
Language:English
Date:14 September 2018
Deposited On:24 Oct 2018 10:11
Last Modified:12 Feb 2019 15:14
Publisher:Elsevier
ISSN:0306-4530
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.psyneuen.2018.09.018
PubMed ID:30318393
Project Information:
  • : FunderSNSF
  • : Grant ID320030_122406
  • : Project TitleThe effects of alpha- adrenergic blockade on norepinephrine-induced changes in blood lipids, procoagulant activity, and inflammatory cytokines in essential hypertension:associations with psychological factors?
  • : FunderSNSF
  • : Grant IDPP00P1_128565
  • : Project TitlePsychoneurobiological mechanisms in essential hypertension and coronary heart disease
  • : FunderGerman Research Foundation
  • : Grant IDINST 38/550-1
  • : Project Title

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