title: Propofol-induced modifications of cardiomyocyte calcium transient and sarcoplasmic reticulum function in rats.
abstract: BACKGROUND
  Propofol is considered to be an anesthetic agent with few or no negative inotropic effects. This study evaluated a possible direct depressant effect of propofol on sarcoplasmic reticulum Ca2+ accumulation and cardiomyocytes.
  
  
  METHODS
  The effects of propofol on intracellular Ca2+ transients were evaluated in isolated rat cardiomyocytes using a microfluorometric technique with Indo-1. Sarcoplasmic reticulum function was also assessed by measuring the oxalate-stimulated Ca2+ uptake from homogenates of rat ventricles.
  
  
  RESULTS
  The Ca2+ uptake capacity of the sarcoplasmic reticulum was decreased by propofol (10(-4) M). Large concentrations of propofol decreased the rate of decrease of the intracellular Ca2+ transient, which resulted in an increase of diastolic Ca2+ when the diastolic interval was decreased. The increased diastolic Ca2+ also resulted in a decrease in Ca2+ transient. This effect appeared for lower doses (10(-5) M) after a short diastolic pause rather than after a long (2- to 3-min) rest (appearing at 10(-4) M).
  
  
  CONCLUSIONS
  For doses more than 10(-5) M, propofol induces a Ca2+ uptake capacity impairment of the sarcoplasmic reticulum. This is probably responsible for a slowing of the decrease of the Ca2+ transient, which in turn increases the diastolic Ca2+ for high heart rate. These diastolic modifications may participate in the slight negative inotropic effect of the drug.
authors.affiliation: Unité Institut National de la Sante et de la Recherche Medicale (INSERM) U400, Faculté de Médecine, Créteil, France. tguenoun@invivo.edu
authors.forename: T
authors.initials: T
authors.lastname: Guenoun
authors.forename: O
authors.initials: O
authors.lastname: Montagne
authors.forename: M
authors.initials: M
authors.lastname: Laplace
authors.forename: B
authors.initials: B
authors.lastname: Crozatier
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002469:Cell Separation; D002614:Chelating Agents; D004558:Electric Stimulation; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005470:Fluorometry; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018686:Anesthetics, Intravenous; D002614:Chelating Agents; D005217:Fat Emulsions, Intravenous; D007211:Indoles; C059587:Indo-1 pentaacetoxymethyl ester; D002118:Calcium; D015742:Propofol