18 Şubat 2013 Pazartesi

Propolis Component Exhibits Cardioprotective, Antiarrhythmic Effects

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Electrophysiological and Mechanical Effects of Caffeic AcidPhenethyl Ester, a Novel Cardioprotective Agent with Antiarrhythmic Activity,in Guinea-Pig Heart
Eur J Pharmacol, 2013 Feb 5Caffeic acid phenethyl ester (CAPE) is an active componentof propolis that exhibits cardioprotective and antiarrhythmic effects. Thedetailed mechanisms underlying these effects, however, are not entirelyunderstood. The aim of this study was to elucidate the electromechanicaleffects of CAPE in guinea-pig cardiac preparations. Intracardiac electrograms,left ventricular (LV) pressure, and the anti-arrhythmic efficacy weredetermined using isolated hearts. Action potentials of papillary muscles wereassessed with microelectrodes, Ca(2+) transients were measured by fluorescence,and ion fluxes were measured by patch-clamp techniques. In a perfused heartmodel, CAPE prolonged the atrio-ventricular conduction interval, the Wenckebachcycle length, and the refractory periods of the AV node and His-Purkinjesystem, while shortening the QT interval. CAPE reduced the occurrence ofreperfusion-induced ventricular fibrillation and decreased LV pressure inisolated hearts. In papillary muscles, CAPE shortened the action potentialduration and reduced both the maximum upstroke velocity and contractile force.In fura-2-loaded single ventricular myocytes, CAPE decreased cell shorteningand the Ca(2+) transient amplitude. Patch-clamp experiments revealed that CAPEproduced 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 anegative-shift of the voltage-dependent inactivation and a delay of recoveryfrom 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 ofCa(2+) inward and Na(+) inward currents by CAPE may induce majorelectromechanical alterations in guinea-pig cardiac preparations, which mayunderlie its antiarrhythmic action.

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