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


CONCLUSIONS
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.
Nakae
Y
Y
Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan. yurinaka@sapmed.ac.jp
Fujita
S
S
Namiki
A
A
D008841:Actin Cytoskeleton / Q000187:drug effects; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002122:Calcium Chloride / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
D018686:Anesthetics, Intravenous; D005456:Fluorescent Dyes; D002122:Calcium Chloride; D015742:Propofol