title: A translational assessment of preclinical versus clinical tools for the measurement of cardiac contractility: comparison of LV dP/dt(max) with echocardiography in telemetry implanted beagle dogs.
abstract: BACKGROUND
  Regarding evaluation of drug-induced changes in left ventricular contractility in safety pharmacology there is still a gap in knowledge between preclinically and clinically used measurements.
  
  
  METHODS
  As a step towards translation of preclinical to clinical outcomes, this study in telemetered dogs was initiated to compare indexes of contractility, such as LV dP/dt(max) (contractility measured as the maximum raise of pressure in the left ventricle) and LV dP/dt(max)/P (contractility measured as the maximum raise of pressure in the left ventricle, corrected for pressure) (telemetry; both commonly preclinically used) and EF (ejection fraction) and FS (fractional shortening) (echocardiography; both commonly clinically used). Different inotropic states were induced by minoxidil, milrinone, isoprenaline, clonidine, atenolol and verapamil.
  
  
  RESULTS
  Both techniques demonstrated reproducible changes in contractility which showed a clear linear association. A change in LV dP/dt(max) of 1000 mmHg/s (in the range of 2500 to 7500 mmHg/s; in healthy dogs) corresponded with a change in ejection fraction of approximately 7% and a fractional shortening of approximately 6%. A change of 10/s LV dP/dt(max)/P (in the range of 35 to 85/s; in healthy dogs) corresponded with a change in ejection fraction of approximately 7% and a fractional shortening of 7%.
  
  
  CONCLUSIONS
  The correlation found in this study could potentially enable a better--translational--assessment of the clinical relevance of changes in contractility indices measured with telemetry devices in preclinical safety studies.
authors.affiliation: Translational Sciences, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: fcools@its.jnj.com.
authors.forename: Frank
authors.initials: F
authors.lastname: Cools
authors.affiliation: Translational Sciences, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: Deborah
authors.initials: D
authors.lastname: Dhuyvetter
authors.affiliation: Translational Sciences, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: Annik
authors.initials: A
authors.lastname: Vanlommel
authors.affiliation: Translational Sciences, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Janssens
authors.affiliation: Translational Sciences, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Borghys
authors.affiliation: Nonclinical Statistics and Computing, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: Helena
authors.initials: H
authors.lastname: Geys
authors.affiliation: Translational Sciences, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: David J
authors.initials: DJ
authors.lastname: Gallacher
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D004452:Echocardiography / Q000379:methods; D005260:Female; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D013686:Telemetry / Q000379:methods; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents
keywords: Beagle dog; C(max); Contractility; EF; Echocardiography; Ejection fraction; FS; Fractional shortening; LV dP/dt(max); LV dP/dt(max)/P; LVP; M-mode; Methods; T(max); TdP; Torsades de pointes; contractility measured as the maximum raise of pressure in the left ventricle; contractility measured as the maximum raise of pressure in the left ventricle, corrected for pressure; ejection fraction; fractional shortening; left ventricular pressure; maximum plasma concentration; motion mode of echo-cardiography; time point of maximum plasma concentration