title: Evaluation of a method utilizing PhysioFlow®, a novel signal morphology-based form of impedance cardiography, to measure cardiac output in the conscious beagle.
abstract: BACKGROUND
  Currently, standard methods for measuring cardiac output are either invasive (i.e. flow probe) or are limited in terms of short measurement intervals and measurement variability (i.e. echocardiography). The ability to reliably measure cardiac output in a non-invasive manner in large animals would provide a valuable tool to expand functional cardiovascular endpoints in preclinical safety studies. PhysioFlow® is a novel method that uses waveform analysis of an impedance signal to measure cardiac output non-invasively. Unlike cardiac impedance techniques in the past, PhysioFlow® is not dependant on thoracic structure or basal thoracic impedance (Z0) and therefore this methodology is transferrable from human to animal models.
  
  
  METHODS
  Three tool compounds with known effects on cardiac output were administered to conscious beagle dogs to determine if the non-invasive PhysioFlow® system could detect the expected changes in stroke volume and cardiac output as determined by literature references using the current standard methodologies (e.g. aortic blood flow and thermodilution).
  
  
  RESULTS
  The PhysioFlow® system was able to detect increases in cardiac output when dosed with 20μg/kg of Dobutamine, a decrease in cardiac output when dosed with 0.1mg/kg of Acepromazine, and no significant change in cardiac output when dosed with 2mg/kg of Minoxidil. These results are within expected ranges based on published literature (Stepien et al., 1995; Taylor et al., 2007).
  
  
  CONCLUSIONS
  PhysioFlow®, a signal morphology-based impedance cardiography, can be utilized to reliably and non-invasively measure cardiac output in beagle dogs.
authors.affiliation: Safety Pharmacology, GlaxoSmithKline, 709 Swedeland Rd, King of Prussia, PA 19406, United States.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Payseur
authors.affiliation: Safety Pharmacology, GlaxoSmithKline, 709 Swedeland Rd, King of Prussia, PA 19406, United States.
authors.forename: John J
authors.initials: JJ
authors.lastname: Rigney
authors.affiliation: Safety Pharmacology, GlaxoSmithKline, 709 Swedeland Rd, King of Prussia, PA 19406, United States.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Turner
authors.affiliation: Safety Pharmacology, GlaxoSmithKline, 709 Swedeland Rd, King of Prussia, PA 19406, United States.
authors.forename: XueJun
authors.initials: X
authors.lastname: Wu
authors.affiliation: Safety Pharmacology, GlaxoSmithKline, 709 Swedeland Rd, King of Prussia, PA 19406, United States.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Murphy
authors.affiliation: Safety Pharmacology, GlaxoSmithKline, 709 Swedeland Rd, King of Prussia, PA 19406, United States.
authors.forename: Eric I
authors.initials: EI
authors.lastname: Rossman
mesh_terms: D000075:Acepromazine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects*; D002307:Cardiography, Impedance / Q000295:instrumentation*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D018492:Dopamine Antagonists / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008914:Minoxidil / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects; D058067:Wavelet Analysis
chemical_list: D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D018492:Dopamine Antagonists; D004280:Dobutamine; D000075:Acepromazine; D008914:Minoxidil
keywords: Acepromazine; Beagle; Cardiac output; Dobutamine; Dog; Methods; Minoxidil; PhysioFlow®