Propofol-induced modifications of cardiomyocyte calcium transient and sarcoplasmic reticulum function in rats.
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.
Guenoun
T
T
Unité Institut National de la Sante et de la Recherche Medicale (INSERM) U400, Faculté de Médecine, Créteil, France. tguenoun@invivo.edu
Montagne
O
O
Laplace
M
M
Crozatier
B
B
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*
D018686:Anesthetics, Intravenous; D002614:Chelating Agents; D005217:Fat Emulsions, Intravenous; D007211:Indoles; C059587:Indo-1 pentaacetoxymethyl ester; D002118:Calcium; D015742:Propofol