心臟衰竭之研究與藥物探索─心電生理特性，抗心律不整效力及不整脈誘發性之測定，包括CARVEDILOL及THALIDOPARHINE等新衍發物(3/3)
Date Issued
2001
Date
2001
Author(s)
吳美環
DOI
892320B002253M48
Abstract
Background. We have identified the compound,
liriodenine, to possess an antiarrhythmia
potential and a positive inotropic effect.
Methods. The direct modification by various
interventions on cardiac conduction system was
performed by intracardiac recording and
stimulation in isolated, Langendorff perfused
hearts. The changes were measured in the hearts
isolated from rats and rabbits.
Results. The changes of the electrophysiological
parameters after liriodenine were determined in
10 rats. At low concentrations, 0.3 to 1 mM, the
cardiac conduction and the refractoriness of the
cardiac conduction system were not
significantly altered by liriodenine. At higher
concentrations, 3 and 10 mM, liriodenine could
significantly prolong the conduction over the
heart, including the intratrial conduction (SA
interval), atrioventricular conduction (AH
interval), conduction over the His-Purkinje
system (HV interval). The refractory period of
the atrioventricular nodal, His-Purkinje system
and ventricular tissue were also significantly
prolonged. But, the sinus cycle length and the
atrial refractory period were not changed.
However, ventricular tachyarrhythmias could be
induced by ventricular extrastimulation at 3 mM
(one rat) and 10 mM (4 rats) liriodenine infusion.
In the ischemia-reperfusion model, liriodenine
could convert the reperfusion ventrciualr
arrhythmia with an EC50 of 0.3 mM.
Conclusions. After the delineation of the
inhibitory effects of liriodenine on the ionic
currents (INa, ICa, Ito, and IK1) in isolated rat
ventricular myocytes, the electrophysiological
study in Langendorff-perfused isolated rat
hearts defined its electrophysiological
modulation by drugs. Liriodenine at low
concentrations could effectively convert the
reperfuion arrhythmias, but at high
concentration that 30 folds higher than the EC50
for conversion of the reperfusion arrhythmias
might induce ventricular arrhythmia via
extremely prolonged centrciualr refractoriness
and QT intervals.
Publisher
臺北市：國立臺灣大學醫學院小兒科
Type
report
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