Eur J Pharmacol, 2013 Feb 5
Caffeic acid phenethyl ester (CAPE) is an active component
of propolis that exhibits cardioprotective and antiarrhythmic effects. The
detailed mechanisms underlying these effects, however, are not entirely
understood.
The aim of this study was to elucidate the electromechanical
effects of CAPE in guinea-pig cardiac preparations. Intracardiac electrograms,
left ventricular (LV) pressure, and the anti-arrhythmic efficacy were
determined using isolated hearts. Action potentials of papillary muscles were
assessed with microelectrodes, Ca(2+) transients were measured by fluorescence,
and ion fluxes were measured by patch-clamp techniques. In a perfused heart
model, CAPE prolonged the atrio-ventricular conduction interval, the Wenckebach
cycle length, and the refractory periods of the AV node and His-Purkinje
system, while shortening the QT interval. CAPE reduced the occurrence of
reperfusion-induced ventricular fibrillation and decreased LV pressure in
isolated hearts. In papillary muscles, CAPE shortened the action potential
duration and reduced both the maximum upstroke velocity and contractile force.
In fura-2-loaded single ventricular myocytes, CAPE decreased cell shortening
and the Ca(2+) transient amplitude. Patch-clamp experiments revealed that CAPE
produced a use-dependent decrease in L-type Ca(2+) current (I(Ca,L))
(IC(50)=1.1μM) and Na(+) current (I(Na)) (IC(50)=0.43μM), caused a
negative-shift of the voltage-dependent inactivation and a delay of recovery
from inactivation. CAPE decreased the delayed outward K(+) current (I(K))
slightly, without affecting the inward rectifier K(+) current (I(K1)).
These results suggest that the preferential inhibition of
Ca(2+) inward and Na(+) inward currents by CAPE may induce major
electromechanical alterations in guinea-pig cardiac preparations, which may
underlie its antiarrhythmic action.
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