PROPOFOL AND KETAMINE ONLY INHIBIT INTRACELLULAR CA2+ TRANSIENTS AND CONTRACTION IN RAT VENTRICULAR MYOCYTES AT SUPRACLINICAL CONCENTRATIONS

Background: The cellular mechanisms that mediate the cardiodepressant effects of intravenous anesthetic agents remain undefined. The objecti ve of this study was to elucidate the direct effects of propofol and k etamine on cardiac excitation-contraction coupling by simultaneously m easuring intracellular calcium concentration ([Ca2+](i)) and shortenin g in individual, field-stimulated ventricular myocytes. Methods: Fresh ly isolated rat ventricular myocytes were loaded with the Ca2+ indicat or, fura-2, and placed on the stage of an inverted fluorescence micros cope in a temperature-regulated bath, [Ca2+](i) and myocyte shortening (video edge detection) were monitored simultaneously in individual ce lls that were field-stimulated at 0.3 Hz. Results: Baseline [Ca2+](i) (mean +/- SEM) was 80 +/- 12 nM, and resting cell length was 112 +/- 2 mu m. Field stimulation increased [Ca2+](i) to 350 +/- 23 nM, and the myocytes shortened by 10% of diastolic cell length. Both intravenous anesthetic agents caused dose-dependent decreases in peak [Ca2+](i) an d shortening, At 300 mu M, propofol prolonged time to peak concentrati on and time to 50% recovery for [Ca2+](i) and shortening, In contrast, changes in time to peak concentration and time to 50% recovery in res ponse to ketamine were observed only at the highest concentrations, Ne ither agent altered the amount of Ca2+ released from intracellular sto res in response to caffeine. Propofol but not ketamine, however, cause d a leftward shift in the dose-response curve to extracellular Ca2+ fo r shortening, with no concomitant effect on peak [Ca2+](i). Conclusion s:: These results indicate that both intravenous anesthetic agents hav e a direct negative inotropic effect, which is mediated by a decrease in the availability of [Ca2+](i). Propofol but not ketamine may also a lter sarcoplasmic reticulum Ca2+ handling and increase myofilament Ca2 + sensitivity. The effects of propofol and ketamine are primarily appa rent at supraclinical concentrations, however.