KB-R7943对心力衰竭家兔哇巴因诱发心律失常的抑制作用

目的 探讨钠-钙交换体抑制剂KB-R7943对哇巴因诱发心衰家兔心律失常的影响.方法 40只成年家兔随机分为5组：假手术组、心衰对照组、哇巴因组、哇巴因合并KB-R7943（1μmol/L）组和哇巴因合并KB-R7943（5μmol/L）组.心衰组、哇巴因组、哇巴因合并KB-R7943（1 μmol/L）组和哇巴因合并K.B-R7943（5 μmol/L）组使用主动脉瓣关闭不全联合腹主动脉缩窄的方法建立心衰模型.建模8周后超声检测心功能,并利用Langendorff离体心脏灌流方法检测家兔各项离体心功能指标.灌流哇巴因（5μmol/L,4ml）诱发家兔心衰心脏产生心律失常,观察KB-R7943对离体心衰家兔心律失常的影响.结果 ①超声结果显示,与假手术组相比,心衰对照组家兔左室射血分数（LVEF）、短轴缩短率（％FS）均明显降低（P＜0.05）.②离体条件下,心衰对照组家兔离体心脏左室发展压（LVDP）、心率（HR）、室内压最大上升速率（＋dp/dtmax）、室内压最大下降速率（-dp/dtmax）较假手术组均明显下降（P＜0.05）.③哇巴因组1h内总心律失常（TT）、室速（VT）、室颤（VF）持续时间较心衰对照组明显增加（P＜0.05）.④与哇巴因组比较,哇巴因联合应用KB-R7943组1h内TT、VT、VF持续时间明显减短（P＜0.05）;与1 μmol/L KB-R7943相比,5μmol/L KB-R7943可使哇巴因诱发TT和VT时间进一步缩短（P＜0.05）.结论 钠-钙交换体抑制剂KB-R7943可抑制哇巴因诱发心衰家兔心律失常的持续时间,且较高浓度（5 μmol/L）KB-R7943对哇巴因诱发心衰家兔心律失常的抑制作用更强.

The inhibitory effect of KB-R7943 on ouabain induced arrhythmia in rabbits with heart failure

Objective To investigate the effect of KB-R7943,a potent inhibitor of the Na＋/Ca2＋ exchanger,on ouabain-induced arrhythmia in heart failure in rabbits.Methods 40 adult rabbits were randomly divided into five groups：sham-operated （sham,n=8）,heart failure in the control（HF,n=8）,ouabain（n=8）,ouabain plus KB-R7943（1 μ mol/L,n=8） and oubain plus KB-R7943（5 μmol/L,n=8） groups.The heart failure models were established by aortic insufficiency combined with abdominal aorta constriction.Eight weeks after operation,cardiac function were detected using cardiac ultrasound and Langendorff-perfused system both in anaesthetized and in isolated rabbit hearts.Cardiac arrhythmias was induced with ouabain （5 μmol/L,4 ml） and effects of KB-R7943 at 1 μmol/L and 5 μmol/L,respectively on ouabain-induced arrhythmia were observed in failing hearts.Results （1）Compared with the sham group,it was showed that the left ventricular ejection fraction （LVEF） and fractional shortening rate （％ FS） in HF group were significantly reduced by ultrasound detection （P＜0.05）.（2） Compared with sham group,left ventricular developed pressure（LVDP）,heart rate（HR）,the maximal rising rate of left ventricular pressure （＋dp/dtmax） and the maximal falling rate of left ventricular pressure（-dp/dtmax） all decreased in Langendorff-perfused hearts in HF group （P＜0.05）.（3）Duration of the total arrhythmias time（TT）,ventricular tachycardia （VT） and ventricular fibrillation （VF） in ouabain group increased significantly than in HF group （P＜0.05）.（4）Durations of TT,VT and VF decreased significantly in oubain plus KB-R7943 groups when compared with ouabain group （P＜0.05）.Compared with 1 μmol/L KB-R7943 group,TT,VT and VF durations were further reduced in 5 μmol/L KB-R7943 group.Conclusion Sodium-calcium exchanger inhibitor KB-R7943 reduces the durations of arrhythmia induced by ouabain in isolated failing hearts in rabbits,and the inhibitory effect of high co