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 depress ant effect of propofol on sarcoplasmic reticulum Ca2+ accumulation and card iomyocytes. Methods: The effects of propofol on intracellular Ca2+ transients were eval uated in isolated rat cardiomyocytes using a microfluorometric technique wi th Indo-1. Sarcoplasmic reticulum function was also assessed by measuring t he oxalate-stimulated Ca2+ uptake from homogenates of rat ventricles. Results: The Ca2+ uptake capacity of the sarcoplasmic reticulum was decreas ed by propofol (10(-4) M). Large concentrations of propofol decreased the r ate of decrease of the intracellular Ca2+ transient, which resulted in an i ncrease of diastolic Ca2+ when the diastolic interval was decreased. The in creased diastolic Ca2+ also resulted in a decrease in Ca2+ transient. This effect appeared for lower doses (10(-5) M) after a short diastolic pause ra ther 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 respons ible for a slowing of the decrease of the Ca2+ transient, which in turn inc reases the diastolic Ca2+ for high heart rate, These diastolic modification s may participate in the slight negative inotropic effect of the drug.