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19. A translational assessment of preclinical versus clinical tools for the measurement of cardiac contractility: Comparison of LV dP/dtmax with echocardiography in telemetry implanted beagle dogs.

Author

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

Subjects
*CARDIAC contraction, *TRANSLATIONAL research, *MEDICAL needs assessment, *ECHOCARDIOGRAPHY, *BIOTELEMETRY, *MEDICATION safety, *LABORATORY dogs, *LEFT heart ventricle
Abstract

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/dtmax (contractility measured as the maximum raise of pressure in the left ventricle) and LV dP/dtmax/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/dtmax of 1000mmHg/s (in the range of 2500 to 7500mmHg/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/dtmax/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. [Copyright &y& Elsevier]

Published
2014
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