title: Experimental human endotoxemia increases cardiac regularity: results from a prospective, randomized, crossover trial.
abstract: OBJECTIVE
  To determine whether human endotoxemia is associated with a loss of the physiologic beat-to-beat variability of heart rate.
  
  
  METHODS
  Prospective, randomized, crossover, single-blind study.
  
  
  METHODS
  Clinical research center in a federal, nonuniversity hospital.
  
  
  METHODS
  Healthy volunteers.
  
  
  METHODS
  Intravenous administration of reference (Escherichia coli) endotoxin or saline placebo, with or without previous administration of oral ibuprofen.
  
  
  RESULTS
  Electrocardiograms were continuously recorded and digitized using series of 1000 beat epochs of R-R intervals over 8 hrs. Analyses included measures in the time domain (standard deviation), frequency domain (power spectra), and a measure of regularity (approximate entropy). Endotoxin administration was associated with loss of variability by all measures. This loss of variability remained significant even with administration of ibuprofen, which blocked the development of fever and endotoxin-related symptoms.
  
  
  CONCLUSIONS
  Infusion of endotoxin into human volunteers causes loss of heart rate variability, as measured by standard deviation and power spectra, as well as an increase in heart rate regularity, as measured by approximate entropy. Changes in approximate entropy occurred earlier than changes in other heart rate variability measures and may be a useful means of detecting early sepsis. This reduction in regularity is consistent with a model in which the pathogenesis of multiple organ system dysfunction syndrome involves the physiologic uncoupling of vital organ systems.
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Godin
authors.forename: L A
authors.initials: LA
authors.lastname: Fleisher
authors.forename: A
authors.initials: A
authors.lastname: Eidsath
authors.forename: R W
authors.initials: RW
authors.lastname: Vandivier
authors.forename: H L
authors.initials: HL
authors.lastname: Preas
authors.forename: S M
authors.initials: SM
authors.lastname: Banks
authors.forename: T G
authors.initials: TG
authors.lastname: Buchman
authors.forename: A F
authors.initials: AF
authors.lastname: Suffredini
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D018592:Cross-Over Studies; D004562:Electrocardiography; D004731:Endotoxins / Q000097:blood*; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D008297:Male; D011446:Prospective Studies; D016037:Single-Blind Method; D014115:Toxemia / Q000503:physiopathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004731:Endotoxins; D007052:Ibuprofen