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Cardiovascular Research 2004 61(1):77-86; doi:10.1016/j.cardiores.2003.09.022
© 2004 by European Society of Cardiology
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Copyright © 2004, European Society of Cardiology

Quantification of the rat left ventricle force and Ca2+–frequency relationships: similarities to dog and human

David G Taylora, Leonard D Parilakb, Martin M LeWinterc and Harm J Knot*,a,b,c

aDepartment of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, USA
bDivision of Cardiovascular Medicine, University of Florida, Gainesville, FL 32610-0267, USA
cCardiology Unit, Department of Medicine, University of Vermont, Burlington, VT 05401, USA

* Corresponding author. Department of Pharmacology and Therapeutics, PO Box 100267, Gainesville, FL 32610-0267, USA. Tel.: +1-352-392-5317; fax: +1-352-392-9696. hknot{at}college.med.ufl.edu

Objective: To measure and quantify the force–frequency (FFR) and Ca2+–frequency (CaFR) relationships in isolated rat left ventricular (LV) muscle at physiological heart rates and compare the obtained FFR to that measured in larger mammalian muscle from dog and human using the same experimental protocol. Methods: Rat papillary muscle was isolated from the LV of adult male Sprague–Dawley rats, and dog and human muscles were from free-wall LV biopsies, loaded with the Ca2+ indicator Fura-2, allowed to recover from isolation trauma and then subjected to direct electrical stimulation while measuring force production and intracellular Ca2+ transients. Results: We obtained a positive FFR between 1 and 4 Hz that is qualitatively similar to that found in isolated LV epicardial muscle strips from dogs and humans with normal LV function. The FFR reflects the cytosolic Ca2+ transients in amplitude. Isoproterenol yielded an enhancement in force, but flattening of the FFR, whereas cyclopiazonic acid caused depression of FFR amplitude without changing frequency-dependent shape. Conclusion: We describe an experimental protocol that consistently yields positive FFRs in rat, dog and human LV muscle at stimulation rates between 1 and 4 Hz, without significant qualitative differences. We attribute previously observed negative FFR in rat muscle to an increase in SERCA activity early after excision and preparation of the muscle strips.

KEYWORDS e-c coupling; Contractile function; Calcium (cellular); SR (function); Ventricular function


Time for primary review 32 days


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