缬草提取物对慢性心力衰竭室性心律失常兔电生理指标的影响

Effect of Valeriana Officinalis L Extract on Correlated Electrophysiological Parameters of Ventricular Arrhythmias induced by Congestive Heart Failure in Rabbit

目的:观察缬草提取物(VOL)对慢性心力衰竭(CHF)致室性心律失常兔电生理指标的影响。方法:雄性新西兰大耳白兔30只,随机平分为三组:正常对照组(Control组)、CHF模型组(CHF组)和CHF+VOL组(VOL组)。CHF模型组经耳缘静脉推注异丙肾上腺素(0.3mg/kg/天,连续注射3周)诱导;Control组平行推注等体积生理盐水;VOL组对CHF兔持续静脉滴注浓度为50mg/L的VOL。记录各组在体心脏左心室单相动作电位(MAP)主要参数静息膜电位(RMP)、动作电位幅度(APA)、动作电位最大上升速率(Max_(dv/dt))和动作电位复极化恢复时程(APD_(10-90));观察各组室性心律失常诱发周长(BCL)、诱发率和心律失常持续时间;分离单个心室肌细胞后,全细胞膜片钳技术记录心室肌细胞L-型钙电流(I_(Ca-L))及电流-电压(I-V)曲线。结果:与Control组比较,CHF组RMP、APA、Max_(dv/dt)均明显降低,APD10、APD20、APD50和APD90均显著延长(P均<0.01);与CHF组比较,VOL组RMP、APA、Max_(dv/dt)均明显增加,各APD时程均显著缩短(P<0.01)。CHF组诱发室性心律失常BCL、心律失常诱发率和持续时间均大于Control组(P<0.01);VOL组BCL、心律失常诱发率和持续时间均小于CHF组(P<0.01)。当钳制电位为+20mV时,与Control组比较,CHF组心室肌细胞I_(Ca-L)电流密度由(-12.13±0.99pA/pF)下降为(-7.14±0.33pA/pF)(P<0.01);VOL组则较CHF组I_(Ca-L)电流密度明显上升(-10.86±0.50pA/pF)(P<0.01),VOL组I_(Ca-L)的I-V曲线较CHF组明显下移,接近Control组。结论:VOL能显著降低CHF心室肌电生理易损性和室性心律失常易感性,拮抗CHF室性心律失常;其机制可能与VOL可增加心室肌细胞I_(Ca-L)有关。

Objective： To investigate effects of valeriana officinalis L extract （VOL） on correlated electrophys- iological parameters of ventricular arrhythmias induced by congestive heart failure （CHF） in rabbits. Method： The male New Zealand rabbits （n=30） were divide into control, CHF and CHF＋VOL （VOL） groups. The CHF mod- els were induced by injection isoproterenol （0. 3mg/Kg/d for 3 weeks）, and control rabbits were injected 0. 9% NaC1 with same ways. The VOL group rabbits were injected 50mg/L VOL. The main cardioelectrophysiological pa- rameters such as RMP, APA, Maxav/dt and APD10 90, as well as basic cycle length （BCL）, rate and time of induced arrhythmias by recording monophasic action potential （MAP） with Burst-pacing in rabbits in vivo with 50mg/L VOL administration. The L-type calcium current （ICa- L） was recorded via whole-cell patch clamp technique in enzy- matically dissociated single rabbit ventricular myocytes. Results.. Compared with control group, RMP, APA and Maxdv/dt were slgnlllcanuy towerea, as well as /APD10-90 were notably llngereO in CHP rabbit （P of all 〈0.01）1, re- spectively）. Compared with CHF group, VOL could significantlyincrease RMP, APA and V as well shorten APD10-90 inVOL group in vivo （P of all d〈0.01, respectively）. Compared with control group, BCL and persistence time inducing ventricular arrhythmias were significantly lengthened, and occurrence of ventricular arrhythmias were obviously increased in CHF group （P of all d〈0.01, respectively）. However, VOL could obviously shorten BCL and persistence time of ventricular arrhythmias, and decrease rate of inducibility of ventricular arrhythmias with burst-pacing in VOL group in vivo （P of all 〈0.01, respectively）. VOL could markedly increase the current densi- ty of ICa-L, and alter down of current-voltage （I-V） relationship curve in different command potential in CHF ventric- ular myocytes. When command potential was ＋20mV, the current densities of ICa-L were significantly increased from （7.14±0.33）pA/pF in CHF group to （10.86±0.50）pA/pF in VOL group（P〈0.01）with VOL administration. Conclusion： VOL could significantly decrease the vulnerability and susceptibility of ventricular arrhythmias induced by CHF, which was contributed to anti-ventrieular arrhythmias induced by CHF. It is suggested that the mecha- nisms might attribute to that VOL could markedly increase ICa-L in CHF rabbits.