Chronic measurement of left ventricular pressure in freely moving rats

Author:

Stehlin Ellyce1,Malpas Simon C.123,Budgett David M.13,Barrett Carolyn J.2,McCormick Daniel13,Whalley Gillian4,Fu Fumin5,Beil Michael5,Rigel Dean F.5,Guild Sarah-Jane23

Affiliation:

1. Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand;

2. Department of Physiology, University of Auckland, Auckland, New Zealand,

3. Millar Inc, Auckland, New Zealand;

4. Faculty of Social and Health Sciences, Unitec, Auckland, New Zealand; and

5. Novartis Institutes for BioMedical Research, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey

Abstract

Measurements of left ventricular pressure (LVP) in conscious freely moving animals are uncommon, yet could offer considerable opportunity for understanding cardiovascular disease progression and treatment. The aim of this study was to develop surgical methods and validate the measurements of a new high-fidelity, solid-state pressure-sensor telemetry device for chronically measuring LVP and dP/d t in rats. The pressure-sensor catheter tip (2-Fr) was inserted into the left ventricular chamber through the apex of the heart, and the telemeter body was implanted in the abdomen. Data were measured up to 85 days after implant. The average daytime dP/d t max was 9,444 ± 363 mmHg/s, ranging from 7,870 to 10,558 mmHg/s ( n = 7). A circadian variation in dP/d t max and heart rate (HR) was observed with an average increase during the night phase in dP/d t max of 918 ± 84 mmHg/s, and in HR of 38 ± 3 bpm. The β-adrenergic-agonist isoproterenol, β1-adrenergic agonist dobutamine, Ca2+ channel blocker verapamil, and the calcium sensitizer levosimendan were administered throughout the implant period, inducing dose-dependent time course changes and absolute changes in dP/d t max of −6,000 to +13,000 mmHg/s. The surgical methods and new technologies demonstrated long-term stability, sensitivity to circadian variation, and the ability to measure large drug-induced changes, validating this new solution for chronic measurement of LVP in conscious rats.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology

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