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Critical Care
Published in: Critical Care 1/2009

Open Access 01-02-2009 | Research

Cardiac force-frequency relationship and frequency-dependent acceleration of relaxation are impaired in LPS-treated rats

Authors: Olivier Joulin, Sylvestre Marechaux, Sidi Hassoun, David Montaigne, Steve Lancel, Remi Neviere

Published in: Critical Care | Issue 1/2009

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Abstract

Introduction

Frequency-dependent acceleration of relaxation (FDAR) ensures appropriate ventricular filling at high heart rates and results from accelerated sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) activity independent of calcium removal from the cell. Because lipopolysaccharide (LPS) challenge may induce aberrations in calcium trafficking and protein phosphorylation, we tested whether LPS would abolish FDAR in rats.

Methods

Following LPS injection, changes in force-frequency relationship and FDAR were studied in cardiomyocytes, isolated hearts and in vivo by echocardiography. Calcium uptake and phosphatase activities were studied in sarcoplasmic reticulum (SR) vesicle preparations. Western blots of phospholamban and calcium/calmodulin-dependent protein kinase II, and serine/threonine phosphatase activity were studied in heart preparations.

Results

In cardiomyocytes and isolated heart preparations, reductions in time constant of relaxation (τ) and time to 50% relaxation at increasing rate of pacing were blunted in LPS-treated rats compared with controls. Early diastolic velocity of the mitral annulus (Ea), a relaxation parameter which correlates in vivo with τ, was reduced in LPS rats compared with control rats. LPS impaired SR calcium uptake, reduced phospholamban phosphorylation and increased serine/threonine protein phosphatase activity. In vivo inhibition of phosphatase activity partially restored FDAR, reduced phosphatase activity and prevented phospholamban dephosphorylation in LPS rat hearts.

Conclusions

LPS impaired phospholamban phosphorylation, cardiac force-frequency relationship and FDAR. Disruption of frequency-dependent acceleration of LV relaxation, which normally participates in optimal heart cavity filling, may be detrimental in sepsis, which is typically associated with elevated heart rates and preload dependency.
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Metadata
Title
Cardiac force-frequency relationship and frequency-dependent acceleration of relaxation are impaired in LPS-treated rats
Authors
Olivier Joulin
Sylvestre Marechaux
Sidi Hassoun
David Montaigne
Steve Lancel
Remi Neviere
Publication date
01-02-2009
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2009
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc7712

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