Propofol inhibits Ca2+ transients but not contraction in intact beating guinea pig hearts

We investigated whether propofol inhibits Ca2+ transients and left ventricu lar pressure (LVP) in intact beating guinea pig hearts at clinical concentr ations and whether an inhibition of Ca2+ transients br propofol results fro m an impairment of sarcolemmal or of sarcoplasmic reticulum (SR) function. By using a Langendorff's preparation, transmural left ventricular phasic in tracellular Ca2+ concentration ([Ca2+](i)) was measured by the fluorescence ratio of indo-1 emission at 385 nm and 456 run and was calibrated to Ca2transients (in nM). The Ca2+ transients during each contraction were define d as available [Ca2+](i). Sixty hearts were perfused with modified Krebs-Ri nger's solution containing lipid vehicle and propofol (1 and 10 mu M) in th e absence and presence of ryanodine, thapsigargin, and nifedipine, while de veloped LVP and available [Ca2+](i) were recorded. Propofol (10 mu M) decea sed available [Ca2+](i) by 11.0% +/- 1.3% without decreasing developed LVP (% of control, P < 0.05). Propofol(10 mu M) caused a leftward shift in the curve of developed LVP as a function of available [Ca2+](i). Propofol (10 m u M) with nifedipine (1 mu M), but not with ryanodine (1 mu M) or thapsigar gin (1 mu M), decreased available [Ca2+](i) by 15.5% +/- 1.7% (P < 0.05). P ropofol decreases available [Ca2+](i) without decreasing cardiac contractio n, and it enhances myofilament Ca2+ sensitivity in intact beating hearts at clinical concentrations. The inhibition of available [Ca2+](i) by propofol may be mainly mediated by an impairment of sarcoplasmic reticulum Ca2+ han dling rather than the sarcolemmal L-type Ca2+ current.