| Pathogen-induced heart rate changes associated with cholinergic nervous system activation. | |
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MedLine Citation:
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PMID: 21068197 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The autonomic nervous system plays a central role in regulation of host defense and in physiological responses to sepsis, including changes in heart rate and heart rate variability. The cholinergic anti-inflammatory response, whereby infection triggers vagal efferent signals that dampen production of proinflammatory cytokines, would be predicted to result in increased vagal signaling to the heart and increased heart rate variability. In fact, decreased heart rate variability is widely described in humans with sepsis. Our studies elucidate this apparent paradox by showing that mice injected with pathogens demonstrate transient bradyarrhythmias of vagal origin in a background of decreased heart rate variability (HRV). Intraperitoneal injection of a large inoculum of Gram-positive or Gram-negative bacteria or Candida albicans rapidly induced bradyarrhythmias of sinus and AV nodal block, characteristic of cardiac vagal firing and dramatically increased short-term HRV. These pathogen-induced bradycardias were immediately terminated by atropine, an antagonist of muscarinic cholinergic receptors, demonstrating the role of vagal efferent signaling in this response. Vagal afferent signaling following pathogen injection was demonstrated by intense nuclear c-Fos activity in neurons of the vagal sensory ganglia and brain stem. Surprisingly, pathogen-induced bradycardia demonstrated rapid and prolonged desensitization and did not recur on repeat injection of the same organism 3 h or 3 days after the initial exposure. After recovery from the initial bradycardia, depressed heart rate variability developed in some mice and was correlated with elevated plasma cytokine levels and mortality. Our findings of decreased HRV and transient heart rate decelerations in infected mice are similar to heart rate changes described by our group in preterm neonates with sepsis. Pathogen sensing and signaling via the vagus nerve, and the desensitization of this response, may account for periods of both increased and decreased heart rate variability in sepsis. |
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Authors:
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Karen D Fairchild; Varadamurthy Srinivasan; J Randall Moorman; Ronald P A Gaykema; Lisa E Goehler |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-10 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 300 ISSN: 1522-1490 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-03 Completed Date: 2011-04-05 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States |
Other Details:
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Languages: eng Pagination: R330-9 Citation Subset: IM |
Affiliation:
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Dept. of Pediatrics, University of Virginia Health System, Hospital Dr., Charlottesville, VA 22908, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atropine / pharmacology Autonomic Pathways / physiology Bradycardia / etiology, physiopathology Brain Stem / physiology Candida albicans Candidiasis / blood, complications, physiopathology Cholinergic Fibers / drug effects, physiology* Cytokines / blood Efferent Pathways / drug effects, physiology Electrocardiography Ganglia, Sensory / physiology Heart / drug effects, physiopathology Heart Rate / physiology* Infection / blood, complications, physiopathology* Klebsiella Infections / blood, complications, physiopathology Klebsiella pneumoniae Male Mice Mice, Inbred C57BL Proto-Oncogene Proteins c-fos / metabolism Sepsis / mortality, physiopathology Staphylococcal Infections / blood, complications, physiopathology Staphylococcus aureus Telemetry Vagus Nerve / drug effects, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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051609//PHS HHS; 068834//PHS HHS; 64640//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Proto-Oncogene Proteins c-fos; 51-55-8/Atropine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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