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) hr, 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.