title: Influence of acute epinephrine infusion on endotoxin-induced parameters of heart rate variability: a randomized controlled trial.
abstract: OBJECTIVE
  To determine whether the acute anti-inflammatory influence of epinephrine (EPI) extends to changes in heart rate variability (HRV) induced by the prototypical inflammatory stimulus, endotoxin (lipopolysaccharide [LPS]).
  
  
  BACKGROUND
  HRV reflects fluctuating cardiac autonomic inputs and is acutely reduced during the systemic inflammation induced by LPS as well as during severe critical illnesses such as sepsis and traumatic injury. While EPI may diminish proinflammatory cytokine release, it is unknown whether this net anti-inflammatory activity extends to HRV.
  
  
  METHODS
  Healthy volunteers (n = 17) were randomized to either saline + LPS (2 ng/kg) or LPS + antecedent EPI infusion (30 ng/kg/min) from -3 to 6 hours relative to LPS. HRV and blood samples were obtained before EPI and LPS as well as hourly afterward. Plasma cytokines were measured by ELISA. Statistical analysis was by repeated measures analysis of variance. This study was registered at Clinicaltrials.gov and is listed under the following ID number: NCT00753402.
  
  
  RESULTS
  LPS acutely influenced all measured parameters of HRV including standard deviation of the average beat to beat intervals over a 5-minute period, percentage of interval differences of successive interbeat intervals greater than 50 milliseconds and square root of the mean squared differences, high frequency (HF), low frequency, low frequency/HF, and very low frequency (all P < 0.01). EPI infusion reduced the inflammatory cytokine response to LPS as measured by decreased TNFalpha, IL-6, and IL-8 (P < 0.01). Relative to the saline + LPS group, antecedent EPI infusion was associated with further reductions in parameters of HRV measuring vagal/parasympathetic activity including, percentage of interval differences of successive interbeat intervals greater than 50 milliseconds, square root of the mean squared differences, and HF (P < 0.05).
  
  
  CONCLUSIONS
  Prior EPI exposure exerts anti-inflammatory influences but also may reduce vagus nerve activity. Hence, acute EPI administration may be protective against early inflammatory challenges but diminish vagal nerve responsiveness to subsequent stimuli.
authors.affiliation: Division of Surgical Sciences, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
authors.forename: Badar U
authors.initials: BU
authors.lastname: Jan
authors.forename: Susette M
authors.initials: SM
authors.lastname: Coyle
authors.forename: Leo O
authors.initials: LO
authors.lastname: Oikawa
authors.forename: Shou-En
authors.initials: SE
authors.lastname: Lu
authors.forename: Steve E
authors.initials: SE
authors.lastname: Calvano
authors.forename: Paul M
authors.initials: PM
authors.lastname: Lehrer
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Lowry
mesh_terms: D000293:Adolescent; D000328:Adult; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004311:Double-Blind Method; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D013312:Stress, Physiological / Q000276:immunology; D055815:Young Adult
chemical_list: D002317:Cardiovascular Agents; D008070:Lipopolysaccharides; D004837:Epinephrine