title: Cardiac force-frequency relationship and frequency-dependent acceleration of relaxation are impaired in LPS-treated rats.
abstract: BACKGROUND
  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 (tau) 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 tau, 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.
authors.affiliation: EA 2689, IMPRT-IFR114, Université de Lille 2, Lille, France. ojoulin@univ-lille2.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Joulin
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Marechaux
authors.forename: Sidi
authors.initials: S
authors.lastname: Hassoun
authors.forename: David
authors.initials: D
authors.lastname: Montaigne
authors.forename: Steve
authors.initials: S
authors.lastname: Lancel
authors.forename: Remi
authors.initials: R
authors.lastname: Neviere
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D008070:Lipopolysaccharides