Tang, Hai-Ming, Ju, Haisong, Zhao, Shufang, Laduke, Carrie, Hahn, Suzette, Glick, Jim, Carey, Cynthia and Friedrichs, Gregory (2016) Translational assessment of cardiac contractility by echocardiography in the telemetered rat. Journal of Pharmacological Toxicololgical Methods, 77. pp. 24-32. ISSN 1056-8719

Abstract

Introduction: Cardiac contractility was evaluated using standard inotropic agents in rats. We compared indices of cardiac contractility, i.e. LV dP/dt max from telemetry while simultaneously collecting EF (ejection fraction) and FS (fractional shortening) measures from echocardiography. Methods: Male Wistar rats were instrumented with telemetry devices for measurements of blood pressure and left ventricular pressure. Milrinone (PDE III inhibitor) and verapamil (L-type calcium channel blocker) at doses of 0, 3, 10, and 30 mg/kg were administered orally using a 4x4 Latin square crossover study design. Telemetry data was recorded at predose and continuously for 24 hours post dose. Echocardiographic evaluations were conducted once at predose and at 1 and 2 hours after milrinone or verapamil administration, respectively. During the recording of echocardiograms, telemetry data were collected simultaneously. Blood samples were also collected to confirm plasma drug exposure. Results: As expected, milrinone increased LV dP/dt max, EF and FS while verapamil decreased LV dP/dtmax, EF and FS. Linear regression analysis showed a positive correlation between LV dP/dt max and EF or FS (P<0.001) with both test agents. A change in LV dP/dt max of 1000 mmHg/sec was found to correspond with a change in EF and FS of 13 and 16%, respectively in the telemetered rat. Discussion: The correlation between contractility indices assessed by telemetry and echocardiographic methods in rat models has not received much attention to date. Our results with two reference compounds demonstrate that both methods are sensitive to alterations in contractility induced by inotropic agents administered to rats. The high degree of correlation between changes in LV dP/dt max and EF or FS in the rat enables a translational-element of clinical relevance following changes in contractility indices when measured with telemetry devices in preclinical studies.

Item Type:	Article
Keywords:	Cardiac contractility Telemetry Echocardiography Rat dP/dt Ejection fraction Fractional shortening Milrinone Verapamil
Date Deposited:	18 Apr 2016 23:45
Last Modified:	18 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/26224