title: Evaluation of bioimpedance spectroscopy for the measurement of body fluid compartment volumes in rats.
abstract: BACKGROUND
  Bioimpedance spectroscopy (BIS) has been used in human and large animal research to assess body fluid compartment volumes (BFC) such as total body water (TBW), extracellular fluid volume (ECFV), and intracellular fluid volume (ICFV). To date, the application of BIS for determination of BFC in small research animals has been limited.
  
  
  METHODS
  We sought to evaluate the sensitivity and consistency of BIS for the determination of BFC in male SD rats. Thus, in separate series of experiments, we a) compared BFC values determined using BIS to BFC values obtained using radioisotope indicator dilution methods; b) examined day-to-day intra- and inter-rat BFC variability in small (267.8±5.4 g) and large (372.6±5.6 g) rats (n=8/group) as compared to empirical normative mammalian values; c) evaluated the sensitivity of BIS to detect time-dependent responses to repeated administration of a potent diuretic; and d) compared empirically generated BFC data to predicted osmotically-induced ECFV and ICFV shifts in response to i.v. administration of hypotonic (0.3%), isotonic (0.9%) or hypertonic (3.0%) saline (n=6/concentration).
  
  
  RESULTS
  BFC values generated using radioisotope dilution agreed with those generated using BIS. BIS reliably detected differences between small and large rats (p<0.001), and was associated with low (<3.5%) day-to-day, intra-animal coefficient of variation (%=Standard Deviation/mean). BIS detected small reductions (~10%) in ECFV induced by as few as 2 days of the loop diuretic, furosemide, relative to vehicle treatment (70.8±1.5 ml vs. 84.0±1.5 ml; respectively, p<0.05). BIS rapidly detected shifts between ECFV and ICFV in response to osmotic saline challenge, and these responses were similar to physiologically predicted responses.
  
  
  CONCLUSIONS
  The current studies support using BIS as a means of sensitively and reliably performing repeated measurements of BFC in rats of a) differing sizes, b) in response to therapeutic agents known to influence renal sodium handling and c) in response to osmotic challenge.
authors.affiliation: Pharmacological Sciences, Gilead Sciences Inc. Palo Alto, CA, United States. lufei.hu@gilead.com
authors.forename: Lufei
authors.initials: L
authors.lastname: Hu
authors.forename: Tom
authors.initials: T
authors.lastname: Maslanik
authors.forename: Mykolai
authors.initials: M
authors.lastname: Zerebeckyj
authors.forename: Craig F
authors.initials: CF
authors.lastname: Plato
mesh_terms: D000818:Animals; D001823:Body Composition / Q000187:drug effects / Q000502:physiology; D001825:Body Fluid Compartments / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D001834:Body Water / Q000187:drug effects / Q000502:physiology*; D017097:Electric Impedance; D045604:Extracellular Fluid / Q000187:drug effects / Q000502:physiology*; D007275:Injections, Intravenous; D008297:Male; D011865:Radioisotope Dilution Technique; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012965:Sodium Chloride / Q000008:administration & dosage
chemical_list: D012965:Sodium Chloride