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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
de Ruijter
Wouter
W
Department of Anesthesiology, Institute for Cardiovascular Research Vrije Universiteit, VU University Medical Center, Amsterdam, The Netherlands. deruijter@physiol.med.vu.nl
Stienen
Ger J M
GJ
van Klarenbosch
Jan
J
de Lange
Jacob J
JJ
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000187:drug effects* / Q000502:physiology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D018686:Anesthetics, Intravenous; D020746:Calcium Channels, L-Type; D000644:Quaternary Ammonium Compounds; D019831:Sodium-Calcium Exchanger; D013890:Thiourea; C027917:tetramethylammonium; D015742:Propofol