Display options
Cite
Cools F, Dhuyvetter D, Vanlommel A, et al. 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. J Pharmacol Toxicol Methods. 2013;69(1):17-23doi: 10.1016/j.vascn.2013.10.003.
Cools, F., Dhuyvetter, D., Vanlommel, A., Janssens, S., Borghys, H., Geys, H., & Gallacher, D. J. (2014). 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. Journal of pharmacological and toxicological methods, 69(1), 17-23. https://doi.org/10.1016/j.vascn.2013.10.003
Cools, Frank, et al. "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." Journal of pharmacological and toxicological methods vol. 69,1 (2014): 17-23. doi: https://doi.org/10.1016/j.vascn.2013.10.003
Cools F, Dhuyvetter D, Vanlommel A, Janssens S, Borghys H, Geys H, Gallacher DJ. 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. J Pharmacol Toxicol Methods. 2014 Jan-Feb;69(1):17-23. doi: 10.1016/j.vascn.2013.10.003. Epub 2013 Oct 16. PMID: 24140387.
Copy Download .nbib Format: NLM
Share it on

J Pharmacol Toxicol Methods. 2014 Jan-Feb;69(1):17-23. doi: 10.1016/j.vascn.2013.10.003. Epub 2013 Oct 16.

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.

Journal of pharmacological and toxicological methods

Frank Cools, Deborah Dhuyvetter, Annik Vanlommel, Sigrid Janssens, Herman Borghys, Helena Geys, David J Gallacher

Affiliations

  1. Translational Sciences, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: [email protected].
  2. Translational Sciences, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.
  3. Nonclinical Statistics and Computing, Janssen Research & Development, Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.

PMID: 24140387 DOI: 10.1016/j.vascn.2013.10.003

Abstract

INTRODUCTION: 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%.

DISCUSSION: 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.

© 2013.

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

Substances

MeSH terms

Publication Types