| BACKGROUND Recent studies have shown that the homogeneity of myocardialrepolarization increases remarkably during ischemic-reperfusion. The threemyocardial layers, including epicardial (Epi), mid-myocardial (M) and endocardail(Endo) cells are different from each other according to their electrophysiologicalcharacteristics. The growth of transmural dispersion of repolarization is known as animportant factor contributing to ischemic-reperfusion arrthymias. Allocryptopine(ALL), an alkaloid, is extracted from Corydalis decumbens (Thunb) PersPapaveraceae. Several previoius studies have indicated that ALL have potentialexperimental antiarrhythmic effects owing to its isoquinoline structure discovered inmany Chinese herbs，but its antiarrhythmic effect is unclear.OBJECTIVE To discuss the role and ionic mechanism of ALL on TDR inischemic-reperfusion rabbit ventricular myocytes. With monophasic action potential(MAP) recording technique, the changes of TDR of myocardium across theventricular wall were recorded in intact rabbits. The preparations of rabbit ischemia-reperfusion model were used to study the mechanism of genesis of ischemicarrhythmia and the protective effect of ALL. Last, after giving ALL, the patch clamptechnique is used to record the slow delayed rectifier potassium current (Iks), transientoutward potassium current (Ito) and L-type calcium current (ICa,L) in isolated rabbitventricular myocytes. The aim of this study is to fully understand the antiarrhythmiaeffects of ALL in vivo, vitro and cellular levels.METHOD1. The changes of MAPD and TDR of Epi, M and Endo were recordedsimultaneously by the MAP recording technique in12chest-opened rabbit in vivounder normal condition and decreased heart rate condition.2.48health rabbits were randomly divided into acute ischemia group and ALLtreatment group, reperfusion group and ALL treatment group (n=12of each group). The changes of MAPD and TDR of Epi, M and Endo were recordedsimultaneously by MAP recording technique under normal, ischemia, reperfusionand ALL treatment conditions. Meanwhile, the genesis of ischemic arrhythmiaand the protective effect of ALL on the myocardium during acute myocardialischemia-reperfusion were also evaluated.3. Myocytes were isolated from Epi, Mid and Endo regions of rabbit left ventricularfree wall. The APD of three layers, TDR and the main repolarizing currents (Ito、IKsand ICa，L) were recorded with whole-cell patch clamp before and after givingALL.RESULT1. MAPD of Epi, M and Endo myocardium were prolonged when basic cycle length(BCL) was increased by vagal stimulation. MAPD of M cells was significantlylonger than that of Epi or Endo.2. The MAPD in three layers of ventricular myocardium were decreased remarkablyalong with the prolongation of ischemia time. MAPD of M cells was significantlyshortened than that of Epi and Endo during acute ischemia, which was notimproved remarkably during myocardial reperfusion. The increase of TDR in thethree layers of ventricular myocardium leaded to the genesis ofischemic-reperfusion arrhythmias (EADs, DADs, VT/VF etc.). Compared withischemic-reperfusion group, MAPD in the ALL group was increased, the TDRand the incidence of ischemic-reperfusion arrhythmias were decreasedsignificantly.3. After using ALL, APD of Epi and Endo cells were prolonged significantly morethan M cells. The IKsand Itodensities were decreased in three layers, and thedensities and amplitudes of Itowere greatly reduced in M and Epi cells but notEndo, while the densities of IKswere reduced in Endo and Epi other than M cells.The effect of ALL on ICa，Lshowed no significant difference in three layers withALL treatment.4. The blockade effect of ALL on IKs、Itoand ICa,Lwas voltage dependently. Theinactivated time constant of IKswas reduced in Epi and Endo but not in M cells. The activation of Itodecreased and inactivation increased, and the recover time ofinactivation was prolonged after ALL treatment. ALL had little effects on thesteady state activation and inactivation curve of ICa,L. The window current of ICa,Lwas also uneffected. The results suggest that ALL accelerates repolarization byreducing inward and outward repolarizing current and reduces TDR, thusproviding an anti-arrhythmia effect.CONCLUSION1. There is the repolarization heterogeneity and low-rate dependence ofmyocardium across the ventricular wall in intact rabbit, and it is possible thatelectrophysological properties of M cells is the base of TDR.2. The increase of TDR in the three layers of ventricular myocardium is theprimary factor leading to ischemic-reperfusion arrhythmia.3. ALL can reverse change of TDR in ischemic-reperfusion, which is importantmechanism of protective effect on ischemia and reperfusion damage.4. IKs, Itoand ICa,Lare reduced by ALL with different way in three layers ofventricular myocardium. ALL effectively decrease TDR in single cell throughdepressing Itoin M cells and IKsin Epi and Endo cells, which also had noinfluence on window current of ICa,L. It may be partly reason for ALL’s ionicmechanism of anti-arrhythmia effect. |
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