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The Study Of KLN Capsule Anti-TachyaR-Rhythmia In Vitro Pharmacodynamic

Posted on:2013-01-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:X M YuFull Text:PDF
GTID:1114330374984905Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Objective: To investigate the KLN (hereinafter referred to as the KLN) capsules onthe isolated rat heart ventricular myocytes electrophysiological and whether to promote therisk of arrhythmia to explore the impact the KLN capsule of exogenous free radicalscaused by arrhythmia analysis of its mechanism of action.Methods:Experiment1: SPF SD rats were divided into control group, propafenone group andKLN capsule high, medium, low-dose group, the control group and treatment groupbetween the two groups, compared the propafenone group with KLN three dose groups.1.Observation the KLN capsule action potential of isolated rat ventricular myocytesthe APD50, APD90, APA, VMAX, EAD and other electrophysiological parameters, analysisof its mechanism of action.2.Respectively in each group before and after treatment, RR interval, QT interval,QTc, which were compared and analyzed the risk of KLN capsules without promotingarrhythmias.Experiment2: SPF SD rats were divided into control group and the verapamil groupand the KLN capsule high, medium, low-dose group, Langedoff perfusion apparatus forisolated rat heart perfusion ferrous sulfate/ascorbic acid method, copy the exogenous freeradicals induced arrhythmia model, compared to its protective effect of the KLN capsule ofverapamil.Results:Experiment1:1.Compared with the control group, the KLN capsule high, medium-dose group of theAPD50, APD90of both prolonged (p <0.01), and these dose were dependent. Low-dose group was not significant (p>0.05). Comparison group, the propafenone group the APD50,APD90were longer than the KLN capsules three dose groups (P <0.01).2.Compared with the control group, the KLN capsule dose-dependent decreases VMAX,which high-dose group decreases, especially (P <0.01). From group showed, the KLNcapsules three dose groups with propafenone VMAXhad no significant differences (P>0.05).3.Compared with the control group, the lower the APA the KLN capsules can be adose-dependent group comparison shows that in the propafenone group APA KLN capsulelow dose compared to significant differences in the propafenone group APA lower (P<0.01) compared with the high dose group had no significant difference (P>0.05).4.The KLN capsule high medium and low-dose group RR interval after treatmentwere significantly prolonged (P <0.05) and dose-dependent manner.5.The KLN capsules before and after administration of three dose groups of QT andQTc were no significant difference (P>0.05).6.After administration of propafenone group, RR interval, the QT interval and QTcwere significantly prolonged (P>0.05).7.Perfusion process, the KLN capsules three dose groups were not induced by theEAD, the propafenone group had four cases of EAD, which statistics EAD had incidencesignificant difference (P <0.01).Experiment2:1.Compared with the control group, the KLN capsule dose-dependent reduction ofexogenous free radicals induced of VEB, VT occurrence (P <0.01).2.The KLN capsule three dose group and verapamil group were not VF control groupinduced the VF, but no significant statistical difference (P>0.05).3.Compared with the control group, the KLN high dose group arrhythmia appear later(P <0.05). The KLN capsule medium and low-dose group, verapamil group of arrhythmiasalso postponed, but statistics had no significant difference (P>0.05).4.Compared with the control group the KLN capsule three dose groups heart rateslowed down, and was dose-related.5.And control groups KLN capsule high and medium-dose group arrhythmia scorewas significantly lower (P <0.05), while the KLN capsule low dose group, verapamil groupand the control group, had no significant difference (P>0.05).Conclusion: 1.The KLN capsule dose-dependent impact on the normal rat in vitro cardiacelectrophysiology had no effect on the interval QT. Therefore it may have a lowerarrhythmogenic risk.2.The KLN capsule exogenous free radical-induced arrhythmias may have preventiveand therapeutic effect. It can significantly slow down the heart rate, and may have somepreventive effect to the occurrence of malignant ventricular arrhythmias (VT, VF). Itsefficacy is superior Verapamil.3.KLN Capsule of Tachyarrhythmia mechanism may be simultaneously related topotassium channels, sodium channels, calcium channels. It may be both free radicalsscavenging effect, inhibition of calcium overload. It may have a role of the characteristicsof multi-target therapy, which is a similar to the composite role of class III, class Icandclass IV anti-arrhythmic drugs. Tachyarrhythmia may have a good effect, which may havea lower arrhythmogenic risk with good prospects.
Keywords/Search Tags:KLN Capsules, tachyarrhythmia, monophasic action potential, exogenous free radicals
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