Propofol inhibits Ca(2+) transients but not contraction in intact beating guinea pig hearts.

Abstract

We investigated whether propofol inhibits Ca(2+) transients and left ventricular pressure (LVP) in intact beating guinea pig hearts at clinical concentrations and whether an inhibition of Ca(2+) transients by propofol results from an impairment of sarcolemmal or of sarcoplasmic reticulum (SR) function. By using a Langendorff's preparation, transmural left ventricular phasic intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured by the fluorescence ratio of indo-1 emission at 385 nm and 456 nm and was calibrated to Ca(2+) transients (in nM). The Ca(2+) transients during each contraction were defined as available [Ca(2+)](i). Sixty hearts were perfused with modified Krebs-Ringer's solution containing lipid vehicle and propofol (1 and 10 microM) in the absence and presence of ryanodine, thapsigargin, and nifedipine, while developed LVP and available [Ca(2+)](i) were recorded. Propofol (10 microM) decreased available [Ca(2+)](i) by 11.0% +/- 1.3% without decreasing developed LVP (% of control, P < 0.05). Propofol (10 microM) caused a leftward shift in the curve of developed LVP as a function of available [Ca(2+)](i). Propofol (10 microM) with nifedipine (1 microM), but not with ryanodine (1 microM) or thapsigargin (1 microM), decreased available [Ca(2+)](i) by 15.5% +/- 1.7% (P < 0.05). Propofol decreases available [Ca(2+)](i) without decreasing cardiac contraction, and it enhances myofilament Ca(2+) sensitivity in intact beating hearts at clinical concentrations. The inhibition of available [Ca(2+)](i) by propofol may be mainly mediated by an impairment of sarcoplasmic reticulum Ca(2+) handling rather than the sarcolemmal L-type Ca(2+) current. This is the first study of the effects of propofol on intracellular Ca(2+) concentration and myofilament Ca(2+) sensitivity under physiologic conditions in intact isolated beating guinea pig hearts.