Effect Of KLN Capsule On Acute Ischemic Arrhythmias Model And Ventricular Myocytes Potassium Channels

Object：To observe the effect of KLN on canine coronary ligation-induced ventriculararrhythmias, and the effect on guinea pig ventricular myocytes potassium channel, in orderto evaluate the effect of KLN on acute ischemic arrhythmias and to explore the possibleionic mechanisms of KLN.Methods：1. Beagle dogs were randomly divided into model control group (normalsaline), experimental group (KLN0.7695g/kg) and positive control group (propafenone50mg/kg) after5days adaptive feeding. Anterior descending coronary artery was ligated asa two-step ligation to copy the tachyarrhythmia model.13hours later, gave KLN andrecorded ECG before and after the administration at30min,60min,90min,120min,180min and240min.2. The Langendorff perfusion device was used for the digestion andseparation of single guinea pig ventricular myocytes. The ventricular myocytes delayedrectifier potassium current (IK) and inward rectifier potassium current (IK1) were recordedat whole cell patch clamp recording mode before and after the administration of KLN.Observe the changes of IKand IK1currents’ waveform.Results：1. Effect of KLN on acute ischemic arrhythmias:①Premature ventricularcomplexes (PVC):30~240min after the administration of KLN, the PVC number wassignificantly reduced (compared with the model group, P<0.01or P<0.05). Theexperimental group and the positive control group showed no significant difference(P>0.05). KLN could inhibit PVC at54.31±17.2%at the most.②Ventricular tachycardia(VT):30~240min after the administration of KLN, VT time was significantly reduced(compared with the model group, P<0.01or P<0.05). The experimental group and thepositive control group showed no significant difference (P>0.05). KLN could inhibit PVCat60.42±31.63%at the most.2. Effect of KLN on guinea pig ventricular myocytes potassium channel:①IK: low, medium and high dose KLN (2.5mg/ml,5mg/ml,10mg/ml)reduced IKtail current (IK,tail) after5min, made the current density-voltage relationshipcurve down. KLN significantly inhibited IKsand IKs,tial(P<0.01or P<0.05) in adose-dependent manner. Envelope of tails test showed low, medium and high dose KLNsignificantly reduced IK,tailcurrent (P<0.01) in a dose-dependent manner, and made thecurrent density-time curve down.②IK1: low dose KLN showed no significant effect onIK1(P>0.05). Medium and high dose KLN significantly reduced IK1inward current(P<0.01). High doses KLN reduced IK1outward current (P<0.05).Conclusion：1. KLN showed significant effect on acute ischemic arrhythmia. Itseffect lasted from30min to240min after administration, and was stronger between120-180min.2. KLN has a dose-dependent inhibition on IK. High dose KLN also reducedthe inward and outward current of IK1. Which may be the mechanisms of KLN’santiarrhythmic effect.