The Anti-arrhythmic Effects And The Mechanisms Of Oxymatrine

Oxymatrine (OMT) ,which extracted from the pecur Radix SophoraFlavescens,Sophora alooides L and Radix Sophorae Subprostratae belong toQuinolizidine. The antiarrhythmic effects of OMT have been proved. In addition,inhibition sodium currents and increasing calcium currents can explain itsmechanism. At the present time,the relationship between anti-arrhythmia effectsof OMT and potassium current have not been known clear yet. In order to findthe relationship between antiarrhythmic effects of OMT and potassium ionchannel further, we investigated the effects of OMT on ECG,parameters ofcardiac action potential and membrane current of potassium. We expected toobtain a theoretical explanation and supplement of the mechanism ofanti-arrhythmia effects of OMT.Firstly, using an arrhythmia model induced by coronary artery occlusion andreperfusion was applied. The effects of OMT on arrhythmia were investigated inrats. Secondly, the effects of OMT on action potential were studied by usingstandard microelectrode method in isolated guinea pig papillary muscles andrabbit papillary muscles. At last, the effects of OMT on Ik were observed usingwhole cell patch clamp technique in isolated guinea pig ventricular myocytes.I. Effect of OMT on arrhythmia induced by coronary arteryocclusion and reperfusion in ratsEffects of OMT on arrhythmia were studied by using an arrhythmia modelinduced by coronary artery occlusion and reperfusion.The results were shown as follow: OMT 15, 30, 60 mg·kg-1 byintravenously injectionin decreased the duration and the extents of arrhythmiainduced by coronary artery occlusion and reperfusion in dose-dependent mannerin rats.The results of section one showed that OMT effectively antagonized thearrhythmia induced by coronary artery occlusion and reperfusion , decreasedthe number of VP, emergency time of VP, duration of VT and duration ofarrhythmia and the mortality rate.II. Effect of OMT on electrophysiological character inmyocardiumUsing standard microelectrode method, effects of OMT on action potentialin isolated guinea pig and rabbit papillary muscles was observed.The experimental results were shown as follow:1.Effects of OMT on action potential in isolated papillarymuscles of rabbitsResults showed that OMT 0.1,1,10mmol·L-1 dose dependently decreasedaction potential amplititude(APA) , shortened APD50 and APD90. OMT 1mmol·L-1mmol/L decreased APA from control of (127.17±5.45) mV to (109.00±2.04) mV, shortened APD50 and APD90 from control of (136.55±11.11) msand (184.86±5.50) ms to (89.49±9.45) ms and(128.56±6.43) ms respectively.2.Effects of OMT on action potential in isolated guinea pigpapillary musclesOMT significantly shortened APD50 and APD90 in isolated guinea pigpapillary muscles. OMT 1 mmol·L-1 decreased APA from control of (117.02±4.45) mV to(111.14±5.13) mV, shortened APD50 and APD90 from controlof(188.08±11.11) ms and(229.11±9.14) ms to (110.17±18.64) ms and (146.83±17.69) ms, respectively.The results showed that OMT can shorten APD and decrease APA .Theeffects probably result from the facilitating of potassium ion currents. It has beenshown that OMT could shorten APD and decrease APA .The effects probablyresult from the facilitating of potassium ion currentsIII: Effects of OMT on potassium currents in guinea pigventricular myocytesThe effects of OMT on IK in isolated guinea pig ventricular myocytes werestudied by using of whole cell patch clamp technique,The experimential resultswere shown as follow: OMT 1mmol·mL-1 promote IK from (1.26±0.17nA)to(1.50±0.16 nA).ConclusionOMT effectively antagonized the arrhythmia induced by coronary arteryocclusion and reperfusion,decreased the rate of ventricular fibrillation and themortality rate.In isolated tissues , OMT decreased APA and shortened APD indose-dependent manner. The anti-arrhythmia mechanism of OMT maybe relatedto promotion of potassium current .