Negative and positive inotropic effects of propofol via L-type calcium channels and the sodium-calcium exchanger in rat cardiac trabeculae

Conflicting opinions are present in the literature regarding the origin of the negative inotropic effect of propofol on the myocardium. This study aims to resolve these discrepancies by investigating the inotropic effects of propofol the L-type calcium channels and the sodium-calcium exchanger (NCX)...

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Veröffentlicht in:Anesthesiology (Philadelphia) 2002-11, Vol.97 (5), p.1146-1155
Hauptverfasser: DE RUIJTER, Wouter, STIENEN, Ger J. M, VAN KLARENBOSCH, Jan, DE LANGE, Jacob J
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STIENEN, Ger J. M
VAN KLARENBOSCH, Jan
DE LANGE, Jacob J
description Conflicting opinions are present in the literature regarding the origin of the negative inotropic effect of propofol on the myocardium. This study aims to resolve these discrepancies by investigating the inotropic effects of propofol the L-type calcium channels and the sodium-calcium exchanger (NCX). The effect of 20 microg/ml propofol on force development was determined in rat cardiac trabeculae at different pacing frequencies and different extracellular calcium concentrations. Postrest potentiation, sodium withdrawal during quiescence, and the NCX inhibitor KB-R7943 were used to study changes in the activity of the reverse mode of the NCX by propofol. The effect of propofol on steady state peak force depended on pacing frequency and calcium concentration. A negative inotropic effect was observed at pacing frequencies greater than 0.5 Hz, but a positive inotropic effect was observed at 0.1 Hz and low calcium, which cannot be explained by an effect on the L-type calcium channel. Propofol enhanced postrest potentiation in a calcium-dependent manner. Sodium withdrawal during quiescence and the use of the specific NCX inhibitor KB-R7943 provided evidence for an enhancement of calcium influx by propofol the reverse mode of the NCX. The effects of propofol on the myocardium depend on pacing frequency and calcium concentration. The positive inotropic effect of propofol is associated with increased calcium influx the reverse mode of the NCX. The authors conclude that the net inotropic effect of propofol is the result of its counteracting influence on the functioning of the L-type calcium channel and the NCX.
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload
subjects Anesthetics, Intravenous - pharmacology
Anesthetics. Neuromuscular blocking agents
Animals
Biological and medical sciences
Calcium Channels, L-Type - drug effects
Calcium Channels, L-Type - physiology
Dose-Response Relationship, Drug
Male
Medical sciences
Myocardial Contraction - drug effects
Neuropharmacology
Pharmacology. Drug treatments
Propofol - pharmacology
Quaternary Ammonium Compounds - pharmacology
Rats
Sodium-Calcium Exchanger - drug effects
Sodium-Calcium Exchanger - physiology
Thiourea - analogs & derivatives
Thiourea - pharmacology
title Negative and positive inotropic effects of propofol via L-type calcium channels and the sodium-calcium exchanger in rat cardiac trabeculae
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