ABSTRACT
Objective To investigate the effects of Tanshinone Ⅱ A (extracted from Chinese herb medicine Salvia miltiorrhiza Bge.) on ventricular arrhythmias of rabbit hearts induced by ischemia in order to illuminate its mechanism of anti-arrhythmia.Methods Thirty rabbits were randomly (random number)divided into normal group,ischemic group and Tanshinone Ⅱ A group.Model of wedge shaped mass of rabbit left ventricular myocardium with coronary perfusion was prepared,and then by using floating glassy microelectrode,the trans-mural ECG,QT interval,the trans-mural dispersion of re-polarization (TDR) and trans-membrane action potentials from both endocardium and epicardium were simultaneously and wholly recorded.The incidence of ventricular arrhythmia in myocardium was observed after ischemia for thirty min.Results Under the condition of acute ischemia,compared with normal group,the incidence of ventricular arrhythmia and TDR were significantly increased in ischemia group (P ＜ 0.01),while incidence of ventricular arrhythmia and TDR were significantly reduced in tanshinone ⅡA group compared with ischemia group (P ＜ 0.05).The incidences of ventricular arrhythmia in normal,ischemia and Tanshinone Ⅱ A groups were 0/10,9/10 and 2/10 respectively.Conclusions Tanshinone Ⅱ A prevents ventricular arrhythmia and reduces TDR significantly in ischemic rabbit hearts.
ABSTRACT
Objective To investigate the aging-related changes in gap junction protein-connexin 43 (Cx 43) in rats and their effect on the high incidence rate of ventricular arrhythmia in aged rats. Methods The 64 healthy male Fischer 344 (F344) rats were randomly divided into four age groups (n=16,each): 3-6 months (juvenile), 9-12 months (young-adult), 18-21 months (middle-aged) and 24-26 months (aged). The incidence rate of ventricular arrhythmia was recorded by monitoring their limb-lead Electroa rdiogram(ECG). Morphological changes of ventricular myocardium were observed under optical microscope in Hematoxylin (HE) and Masson's stain. The distribution of connexins 43 (Cx43) and deophosphatase (NP) Cx43 was observed by confocal immunofluorescence microscopy and the Cx43 and NP-Cx43 protein expression was assessed by Western-Blot. Results The incidence rate of ventricular arrhythmia was much higher in aged group (75.0%) than in other three groups (0%,0%,12.5%), all P＜0.05, and the aged group showed that ventricular muscle cells were hypertrophy and arrayed sparsely and disorderly with hyperplasia of connective tissues. The distribution of Cx43 changed from end-to-end to disordered arrangement and the total expression amount of Cx43 decreased as age increased (P＜0.05). The expression amount of NP-Cx43 in middle-aged rats was notably decreased than in juvenile and aged rats (P＜0.05). Conclusions For aged rats, the high incidence rate of ventricular arrhythmia may be associated with ventricular myocardium reconstruction, disarrangement of ventricular muscle cells and gap junction proteins, decreased expression amount of Cx43 and relatively increased NP-Cx43.
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The possibility of rats mesenchymal stem cells (MSCs) modified with murine hyperpolarization-activated cyclic nucleotide-gated 2 (mHCN2) gene as biological pacemakers in vitro was studied. The cultured MSCs were transfected with pIRES2-EGFP plasmid carrying enhanced green fluorescent protein (EGFP) gene and mHCN2 gene. The identification using restriction enzyme and sequencing indicated that the mHCN2 gene was inserted to the pIRES2-EGFP. Green fluorescence could be seen in MSCs after transfection for 24-48 h. The expression of mHCN2 mRNA and protein in the transfected cells was detected by RT-PCR and Western blot, and the quantity of mHCN2 mRNA and protein expression in transfected MSCs was 5.31 times and 7.55 times higher than that of the non-transfected MSCs respectively (P<0.05, P<0.05). I(HCN2) was recorded by whole-cell patch clamp method. The effect of Cs(+), a specific blocker of pacemaker current, was measured after perfusion by patch clamp. The results of inward current indicated that there was no inward current recording in non-transfected MSCs and a large voltage-dependent inward and Cs(+)-sensitive current activated on hyperpolarizations presented in the transfected MSCs. I(HCN2) was fully activated around -140 mV with an activation threshold of -60 mV. The midpoint (V(50)) was -95.1+/-0.9 mV (n=9). The study demonstrates that mHCN2 mRNA and protein can be expressed and the currents of HCN2 channels can be detected in genetically modified MSCs. The gene-modified MSCs present a novel method for pacemaker genes into the heart or other electrical syncytia.
ABSTRACT
The aim of this study was to determine if the potassium aspartate and magnesium (PAM) prevent reperfusion-induced ventricular arrhythmias (RIVA) in ischemia-reperfusion (IR) rabbit heart. Thirty rabbits were randomly divided into control, ischemia and PAM groups. Arterially-perfused rabbit left ventricular preparations were made, and transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments. In control group rabbit ventricular wedge preparations were continuously perfused with Tyrode's solution, and in ischemia group and PAM groups the perfusion of Tyrode's solution was stopped for 30 min. Then the ischemia group was reperfused with Tyrode's solution and the PAM group with Tyrode's solution containing 2.42 mg/L PAM, respectively. ECG, QT interval, transmural repolarization dispersion (TDR) and action potentials from epicardium and endocardium were simultaneously recorded, and the RIVA of the wedge preparation was observed. Compared with control group, TDR and incidence of RIVA were significantly increased in ischemia group (P<0.05). The incidence of RIVA in control, ischemia and PAM group was 0/10, 9/10 and 1/10, respectively. Compared with ischemia group, TDR and incidence of RIVA were significantly reduced in PAM group (P<0.05). Potassium aspartate and magnesium significantly reduce TDR and prevent ventricular arrhythmia in ischemic rabbit heart.
Subject(s)
Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/prevention & control , Myocardial Ischemia/complications , Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/complications , Potassium Magnesium Aspartate/therapeutic use , Random AllocationABSTRACT
Background and Objective Increased transmural dispersion of repolarization (TDR) has been shown to contribute toinitiation and maintenance of ventricular arrhythmia in long QT syndromes(LQTS).Intercellular uncoupling through gap junctions isan important mechanism for maintaining TDR in both intact and diseased heart.The present study was to test the hypothesis thatimproving gap junction communication reduces TDR and prevents ventricular arrhythmia in rabbit LQT2 model.Methods Anarterially perfused rabbit left ventricular preparation and E-403 (0.5μmol/L)were used to establish a model of LQT2.Preparationswere randomly assigned to control(n=10),AAP-100nmol/L(n=10),AAP-500nM(n=10)groups.Transmural ECG as well as actionpotentials from both endocardium and epieardium was simultaneously recorded. Resuits In LQT2 model.presence of 500nmol/LAAP10 reduced endocardial action potential and TDR and prevented ventricular arrhythmia comparing with the control and AAP 100nmol/Lgroups(P＜0.05).Conclusions The presence of 500 nmol/LAAP10 reduces TDR and prevents ventricular arrhythmia in rabbitventricular model of LOT2.This study suggests a possible role of GJs in TDR in rabbit LQT2 model and indicates a new clinicalapproach to the management of LQTS.
ABSTRACT
Intracellular Ca2+ and Ca2+-dependent signaling molecule play an essential role in the genesis of long-QT (LQT) syndrome-related ventricular arrhythmias. The effect of calcium-channel antagonist verapamil on repolarization heterogeneity of ventricular myocardium was assessed in an in vitro rabbit model of LQT syndrome. By using the monophasic action potential (MAP) recording technique, MAPs of epicardium, mid-myocardium and endocardium were simultaneously recorded by specially designed plunge-needle electrodes across the left ventricular free wall in rabbit hearts purfused by Langendorff method with standard Tyrode's solution. Bradycardia was induced by com-plete ablation of atrioventrtcular node. A catheter was introduced into the right ventricle to pace at the cycle lengths (CLs) of 1500, 1000, and 500 ms, successively. Quinidine (2 μol/L) prolonged QT in-terval and ventricular MAP duration (MAPD), and increased transmural dispersion of repolarization (TDR) in a reverse rate-dependent fashion in isolated rabbit heart. No polymorphic ventricular tachycardias were induced under this condition. The effective free therapeutic plasma concentrations of verapamil (0.01-0.05 μmol/L) used in this experiment had no effect on quinidine-induced changes of QT interval, MAPD and TDR. This study demonstrated that, in this model of LQT syn- drome, blockade of calcium-channel with verapmil had no effect on quinidine-induced changes of repolatiation heterogeneity of ventricular myocardium.