title: Power spectral analysis of heart rate variability in cynomolgus monkeys in safety pharmacology studies: comparative study with beagle dogs.
abstract: BACKGROUND
  Power spectral analysis of heart rate variability is a tool known to provide information of interest on the autonomic control of heart rate in human. However, its use and its conditions of application and interpretation for safety purposes are not well defined for cardiovascular safety pharmacology studies. Likewise, data of power spectral analysis of heart rate variability in cynomolgus monkeys, a species often appropriate for use as second non rodent species in preclinical safety programmes, are not available. This study was designed to evaluate the relevance of this biomarker in this non human primate species, and to compare results with those from beagle dogs under the conditions of safety evaluation studies.
  
  
  METHODS
  Power spectral analysis of heart rate variability was performed on data collected in both species by telemetry following a standard design for cardiovascular safety pharmacology studies. Various pharmacological agents were tested in order to compare the profile of responses in both species after modifying the autonomic nervous balance.
  
  
  RESULTS
  Heart rate variability in cynomolgus monkeys is mainly driven by the parasympathetic nervous system as in beagle dogs although vagal tone is less than in dogs. Power spectral analysis of heart rate variability allows detection of interaction with the autonomic nervous system in both species in all investigated situations, i.e. sympatholytic/sympathomimetic and parasympatholytic/parasympathomimetic drug induced effects. However, due to species difference in the autonomic control of heart rate, cynomolgus monkeys are likely to be more sensitive than beagle dogs for assessment of sympatholytic properties.
  
  
  CONCLUSIONS
  This study confirms that power spectral analysis of heart rate variability from data derived from ECG recordings in telemetry studies is applicable in cardiovascular safety pharmacology studies and may provide relevant information about possible interaction with the autonomic nervous system when new drug entities are evaluated in either species. However, interspecies differences in autonomic control must be taken into account when interpreting possible drug effects.
authors: Centre de Recherches Biologiques, CERB, Chemin de Montifault, 18800 Baugy, France. pascal.champeroux@cerb.fr
authors: Pascal
authors: P
authors: Champeroux
authors: Eric
authors: E
authors: Martel
authors: Sebastien
authors: S
authors: Jude
authors: Christine
authors: C
authors: Laigot
authors: Arnaud
authors: A
authors: Laveissière
authors: Andrée-Anne
authors: AA
authors: Weyn-Marotte
authors: John Sinclair Lawrence
authors: JS
authors: Fowler
authors: Anne
authors: A
authors: Maurin
authors: Serge
authors: S
authors: Richard
authors: Dominique
authors: D
authors: Babuty
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000378:metabolism; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D023421:Models, Animal; D013045:Species Specificity; D013686:Telemetry / Q000379:methods*; D018675:Toxicity Tests / Q000379:methods*
keywords: Beagle dogs; Cynomolgus monkeys; Heart rate variability; Power spectral analysis; Safety pharmacology; Telemetry