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Objective To observe the effects of granulocyte colony stimulating factor (G-CSF) on electrophysiological properties of post-infarct ventricles.Methods Sixty-seven survival Wistar rats were divided into 4 groups:Sham group,Control group,MI early G-CSF group (E-G) and MI delay G-CSF group (D-G) after ligation of the left coronary artery as myocardial infarction model.Monophasic action potential(MAP) was recorded by absorption electrode in ex vivo perfused rat hearts.Effective refractive period(ERP),sinus cardiac length (SCL),action potential amplitude (APA),maximal depolariged (Vmax),ventricular fibrillation threshold(VFF) and ventricular fibrillation duration(VFD) were measured.Results The electrophysiological parameters (SCL,VFT,VFD,APA,ERP/MAP90,dispersion of ERP and MAP90) of the E-G group were improved significantly (all P ＜ 0.05) at day 7 post MI.Improvement in SCL,dispersion of ERP and MAP 90 were found in the D-G group as well at day 7 post MI (all P ＜ 0.05).Substained improvement in electrophysiological parameters were found in the E-G group at 3 months after MI (P ＜0.05).Besides SCL,APA,Vmax and dispersion of MAP90,all other parameters in the D-G group were similar to that of the control group with no statistical significance and even had a tendency of deterioration in ERP and MAP90 3 months after MI.Conclusion G-CSF intervention could improve electrophysiological properties of ischemic ventricles.Early G-CSF intervention showed better outcomes compared to delay G-CSF intervention on electrical remodeling ischemia myocardiumwhich may have effect on reducing the development of ventricular arrhythmia.
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Aim To investigate the effect of mallotoxin (MTX) on LQT2 induced by E-4031 in isolated guinea pig hearts and ventricular myocytes.Methods The isolated guinea pig heart underwent retrograde perfusion using Langendorff technique.In order to determine the effects of different concentrations of MTX on QT/QTc interval,transmural dispersion of repolarization (TDR) and index of cardiac electrophysiological balance (iCEB) in the absence and presence of hERG channel blocker E-4031,the electrocardiogram of isolated guinea pig hearts was recorded using Biopac physiological record.Single ventricular myocytes were isolated from guinea pig heart by enzymatic dissociation.Effects of MTX on action potential duration (APD) in the absence and presence of E-4031 were recorded by current clamp mode using whole patch clamp technique.Results MTX shortened the QT interval,reduced TDR,and decreased iCEB in isolated guinea pig heart.MTX could reverse the prolongation of QT interval and the increased TDR induced by E4031.MTX shortened the action potential duration and decreased APDgo,APD60 and APD30 in isolated guinea pig ventricular myocytes.MTX could reverse the prolongation of action potential repolarization duration induced by E-4031.Conclusion MTX shortens QT interval,decreases TDR,reduces iCEB,as well as shortens APD,thus reversing LQT2 induced by E4031.
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Objective: To observe the effect of ivabradine (IVA) on atrial and ventricular monophasic action potential duration (MAPD) and its proarrhythmic action at presence of sea anemone toxin-II (ATX-II) in isolated rabbit heart modelin vitro. Methods: The perfusion of isolated heart from female New Zealand white rabbit was conducted by Langendorff method in vitro. Left atrial and left ventricular endo- , epi-cardial action potential were recorded when pacing with ifxed frequency of 350 ms (in correspondence with the heart rate of 171 times/min) to observe the effect of IVA alone and ATX-II (3 nmol/L) with IVA on MAPD90. In addition, to observe the action of IVA alone and ATX-II with IVA on proarrhythmia when IVA reducing the heart rate to autonomous cardiac rhythm as (156±10) times/min. Results: IVA at (3-10) μmol/L prolonged atrial and ventricular endo- , epi-cardial MAPD90 by (15.9 ± 2.0) ms, (31.5 ± 4.0) ms and (23.9 ± 3.0) ms (n=6,P<0.01), respectively. ATX-II at 3 nmol/L prolonged atrial and ventricular MAPD90 by (36.5 ± 5.0)ms and (19.9 ± 3.0) ms, (19.5 ± 4.0) ms (n=6,P<0.01) respectively. With ATX-II treatment, IVA at (6-10) μmol/L decreased atrial MAPD90 by (14.4 ± 4.0) ms (n=6,P<0.01), it induced atrial arrhythmia. With 3 nmol/L of ATX-II treated ventricle, IVA at (3-10) μmol/L obviously prolonged endo- and epi-cardial MAPD90 by (36.2 ± 7.0) ms and (27.5 ± 5.0) ms(n=6,P<0.01), respectively. IVA didn’t increase ventricular beat-to-beat variability and transmural dispersion of MAPD90 no matter with or without ATX-II treatment, no ventricular arrhythmia occurred. Conclusion: IVA prolongs both atrial and ventricular MAPD, with increased late sodium current, IVA may induce atrial arrhythmia but not ventricular arrhythmia in experimental rabbits in vitro.
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BACKGROUND:Ventricular arrhythmia (VA) is one of the most common complications of myocardial infarction (MI), and ventricular tachycardia and fibrillation are the main causes for sudden cardiac death. This study aimed to explore the effect of ramipril on the occurrence of VA and its mechanism after MI in rabbits. METHODS:Twenty-four New Zealand rabbits purchased from the Wuhan Laboratory Animal Research Center were divided into three groups:sham-operated (SHAM) group (n=8), MI group (n=8) and MI with ramipril (RAM) group (n=8). Rabbits in the SHAM group received a median sternotomy without ligation of the left ventricular coronary artery. Rabbits in the MI and RAM groups received a median sternotomy followed by ligation of the left coronary artery. The successful anterior MI was confirmed by elevation of the ST segment with more than 0.2 mV in lead II and III. After MI, rabbits in the RAM group were fed with intragastric ramipril (1 mg/kg per day ) for 12 weeks. Before and 12 weeks after MI in the three groups, ventricular tachycardia or fibrillation (VT/VF) episodes and MAP in cadiocytes of the epicardium, mid-myocardium and endocardium were recorded by a multichannel physiograph. Student'st test and ANOVA were used for statistical analysis. RESULTS:VT/VF episodes were decreased more markedly in the RAM group than in the MI group after 12 weeks (2.6±0.8 vs. 12.4±2.9,P<0.05). Twelve weeks after MI, the duration of repolarization for 90％ (APD90) of three-tier ventricular myocytes in the MI group was longer than that before MI (258.2±21.1 vs. 230.1±23.2, 278.0±23.8 vs. 245.8±25.4, 242.6±22.7 vs. 227.0±21.7,P<0.05). However, the APD90 was not significantly different at 12 weeks before and after MI in the RAM group (P>0.05). Moreover, the transmural dispersion of repolarization (TDR) was increased more markedly 12 weeks after MI in the MI group than in the SHAM and RAM groups (36.2±10.2 vs. 18.7±6.2, 24.9±8.7,P<0.05). But the TDR was not significantly different between the RAM and SHAM groups (18.7±6.2 vs. 24.9±8.7,P>0.05). CONCLUSION:Ramipril may reduce the incidence of malignant ventricular arrhythmia via improvement of transmembrance repolarization heterogeneity after MI.
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Objective:To evaluate and screen the anti-atrial ifbrillation drug with multiion channel targets by micro-electrode chip technology in a rapid atrial pacing (RAP) rabbit model. Methods:A total of 32 rabbits were randomly divided into 4 groups, n=8 in each group. Potassium channel blocker (TEA) group, Potassium channel blocker (BaCl2) group, Potassium channel blocker (CdCl2) group and Amiodarone group. The electrode was inserted into right atrium via internal jugular vein with rapid right atrial pacing (600 beat/min) and the effect of each anti-atrial ifbrillation drug on ifeld action potential (fAPD) were measured in different groups. Results:With 24 hour RAP, the fAPD was prolonged from (176.67 ± 8.66) ms to (196.11 ± 10.76) ms, P=0.012 in TEA group;from (182.22 ± 12.87) ms to (191.11 ± 13.09) ms, P=0.039 in BaCl2 group;from (178.33±7.85) ms to (206.67 ± 9.70) ms, P=0.0015 in CdCl2 group;from (167.38 ± 13.67) ms to (185 ± 15.14) ms, P=0.002 in Amiodarone group. Conclusion: RAP induced atrial fibrillation in experimental rabbit model is a simple and feasible method for screening the anti-atrial fibrillation drugs, combining with micro-electrode chip technology, it might be used for developing the new product.
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Objective To investigate the effects of pioglitazone on atrial ionic channel remodeling in alloxan-induced diabetic rabbit models.Methods A total of 32 rabbits were randomly (random number) divided into control (CN) group,diabetes mellitus (DM) group,diabetes mellitus + pioglitazone 4 mg/ (d · kg) (DPG) group and diabetes mellitus + double pioglitazone 8 mg/ (d · kg) (DPI) group.The diabetic state was examined by quantitative determination of blood glucose levels of ≥ 14 mmol/L.Langendorff-perfused rabbit hearts were used to isolate single atrial myocyte,and whole-cell patch-clamp technique was used to record action potential duration (APD) and atrial ionic channel currents (ICa,L and INa).Variables with normal distribution were compared with One-way ANOVA and LSD-t test.Results Compared with controls,APD90 and APDS0 of left atrial myocytes were significantly prolonged in DM group (P ＜0.05 vs.CN),and there was no significant difference in APD90 frequency adaptation between them (P ＞0.05 vs.CN).The densities of INa were reduced and the densities of ICa,L were increased in DM group (P ＜ 0.01 vs.CN).The above variables were markedly attenuated in DPG and DPI group.Conclusions Pioglitazone may inhibits atrial ionic channel remodeling in diabetic rabbit models.
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In this study, electrical and structural remodeling of ventricles was examined in tachycardia-induced heart failure (HF). We studied two groups of weight-matched adult male mongrel dogs: a sham-operated control group (n=5) and a pacing group (n=5) that underwent ventricular pacing at 230 bpm for 3 weeks. Clinical symptoms of congestive HF were observed in both groups. Their hemodynamic parameters were determined and the severity of the HF was evaluated by M-mode echocardiography. Changes in heart morphology were observed by scanning electron and light microscopy. Ventricular action potential duration (APD), as well as the 50 and 90% APD were measured in both groups. All dogs exhibited clinical symptoms of congestive HF after rapid right ventricular pacing for 3 weeks. These data indicate that rapid, right ventricular pacing produces a useful experimental model of low-output HF in dogs, characterized by biventricular pump dysfunction, biventricular cardiac dilation, and non-ischemic impairment of left ventricular contractility. Electrical and structural myocardial remodeling play an essential role in congestive HF progression, and should thus be prevented.
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Animals , Dogs , Male , Action Potentials/physiology , Heart Failure/physiopathology , Hemodynamics/physiology , Tachycardia/complications , Ventricular Remodeling/physiology , Cardiac Pacing, Artificial/methods , Echocardiography , Electric Conductivity , Heart Failure/etiology , Myocardium/pathology , Ventricular FunctionABSTRACT
Objective To determine whether specific angiotensin-conventing enzyme inhibitor with ramipril would affect ventricular arrhythmia generation in rabbits after myocardial infarction and discuss the mechanism of its antiarrhymic efficacy.MethodsTwenty-four New Zealand rabbits (Wuhan Laboratory Animal Research Center) were separated into 3 groups:sham-operated (SHAM) group (n =8 ),myocardial infraction (MI) group ( n =8) and myocardial infraction with ramipril (RAM) group ( n =8).SHAM group received a median sternotomy without left ventricular coronary artery ligation.MI and RAM groups' rabbits received a median sternotomy followed by left coronary artery ligation. The successful anterior MI was confirmed by elevation of the ST segment with more than 0.2 mV in lead Ⅱ and Ⅲ.After MI,RAM group rabbits were fed with ramipril [ 1mg/ ( kg · d) ]by intragastric administration for 12 weeks.Before and after MI 12 weeks in three groups.Ventricular tachycardia or fibrillation episodes and the monophasic actionpotential duration in epicardium,mid-myocardium and endocardium cadiocytes were recorded.The statistical technique was t-test and ANOVA.Results Ventricular tachycardia or fibrillation episodes were markedly decreased in RAM group than that in MI group after 12 weeks [ (2.6 ± 0.8) vs.(12.4 ± 2.9),P ＜0.05 ].After MI 12 weeks,the action potential duration of repolarization 90％ (APD90) of three-tier ventricular myocytes in MI group was prolonged than that before MI [ (258.2 ±21.1 ) vs.(230.1 ±23.2),( 278.0±23.8 ) vs.(245.8±25.4),(242.6±22.7) vs.(227.0±21.7),P＜0.05]; however,it was not significant difference between before and after MI 12w in RAM group (P ＞ 0.05 ).Moreover,the transmural dispersion of repolarization(TDR) was markedly increased after MI 12w in MI group than in SHAM and RAM group [ (36.2 ± 10.2 ) vs.( 18.7 ± 6.2 ),(24.9 ± 8.7 ),P ＜ 0.05 ]; but the TDR was not significant difference between RAM and SHAM group ( 18.7 ± 6.2 ) vs.( 24.9 ± 8.7 ),P ＞ 0.05].ConclusionsRamipril significantly reduced the malignant arrhythmia incidence in rabbits after MI.Mended the abnormal TDR was the mechanism for ramipril to therapy.
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Objective To study the intervention effect of tanshinone on electrophysiological abnormality of hypertrophic cardicoyte in order to illuminate the underlying mechanism of tanshinone in preventing the arrhythmia induced by myocardial hypertrophy. Method Twenty-week-rid SD rats (200～250 g) were divided into 4 groups (8 in each group) randomly. Of 4 groups, rats of three groups were operated on by a procedure of 'one kidney one clamp' to make renal artery constriction. The rest group served as sham operation group (control group). When the blood pressure increased,rats of operation groups were divided into tanshinone group, captopril group and hyper-trophic group. The effects of tanshinoe and captopril were observed and compared on the action potential duration (APD),L-type calcium current (ICa, L) and transient outward potassium current (Ito) density in cellular membrane of hypertrophic myocardium by using patch clamp and intra-cellular calcium survey technique. Results The blood pressure in operation groups was obviously higher than that in sham-operation group (P<0.01), but there was no difference between operation groups (P>0.05). The ratio of ventricle weight to body weight (VW/BW) was much higher in hypertrophic group than in control group (P<0.01), and it significantly decreased after interven-tion with tanshinone or captopril (P<0.01). Compared with hypertrophic group, tanshinone markedly shortened the prolongation of action potential duration (P<0.01), decreased membrane capacity and peak amplitude of ICa,L(P<0.01), but had no effect on the density of ICa,L. Tanshinone also significantly increased Ito current density and peak amplitude, which were completely different from hypertrophic group (P<0.05). There were similar results foundin captopril intervention. Conclusions Tanshinone could reduce calcium influx and resume the activity of ho ion channels, and thus shorten the first phase and the plateau phase of repolarization and decrease the prolongation of APD in hypertrophic cadiocyte. So tanshinone can prevent the onset of arrhythmia attributed to the myocardial hypertrophy.
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Objective To explore the mechanism underlying the superiority of the biphasic waveform to monophasic waveform in defibrillation.Method The Luo-Rudy model was adjusted so that it could be used to study defibrillation.Based on the adjusted model the effects of different defibrillation waveforms on cell action potential duration(APD) were studied.Result Biphasic electrical field pulse extended the APD longer than that with monophasic one.Moreover,biphasic waveforms with different strengths could prolong the APD almost equally,while monophasic pulses with different strengths showed different ability to prolong the APD and the spatial distribution of the APD became dispersed.It was also found that the strength of electrical fields pulse contributed much to the change of APD while the duration showed little effect.Conclusion The clinical superiority of biphasic pulses to monophasic pulses in defibrillation is resulted from its ability to prolong the time course of the APD and more importantly,it causes even spatial distribution of the APD.
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Objective To Study the effect of Gross Saponins of Tribulus Terrestris on active potential and potassium current of ischemic cardiocytes in guinea pigs,and approach its initial anti-arrhythmia effect and mechanism.Methods The cardiocytes of adult guinea pigs were isolated and hypoxia models were set up,the effects of injected GSTT on the cellular membrane active potential and electricity flow of potassium channel were recorded with whole cell patchclamp system.Results Compared with model group,the active plateau period(50% and 90%) of myocytes in GSTT 30 mg?L-1 group prolonged(P
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Objective To study the complex restitution relation between the present action potential duration (APD) and its previous diastole interval (DI) and APD. Method The Luo-Rudy model was paced with different protocols to draw the coordinate curves between the present APD and its first previous DI. These curves were fit with the artificial neural network (ANN). Result Different pacing protocols caused different coordinate curves, and there was no one-to-one relation between pre-sent APD and its first previous DI. ANN fits these curves satisfactorily. Conclusion There is a complex relation between the present APD and the APDs and Dis of the first three previous beats. This relation can be modeled accurately with ANN.
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BACKGROUND AND OBJECTIVES: It remains to be defined how K[ATP] Channel Opener facilitates to induce ventricular arrhythmias. The purposes of this study are to assess the effects of K[ARP] Channel Opener, PCO400, on the action potential duration (APD) and APD restitution (APDR) kinetics, and their relationship with induction of ventricular tachycardia (VT)/fibrillation (VF), pro-fibrillatory effects. MATERALS AND METHODS: We recorded transmembrane potentials (TMPs) by microelectrode technique to explore the effects of PCO400 in ninetecn isolated perfused swine right ventricles. TMPs were recorded on the endoeardial side at the concentrations 0 micrometer, 1 micrometer, 2.5 micrometer, 5 micrometer, 10 micrometer, and washed-out period (1 hour). Ventricular refractory periods were measured while scanning djastole with premature ventricular beats during pacing at the cycle length of 600 ms at each concentration. The maximal slopes (Smax) of APDR were calculated with the data of S1S2 pacing and VF. RESULTS: PCO400 reduced APD90 (208+/-76 ms to 41+/-9 ms during S1, p<0.001, 111+/-32 ms to 54+/-28 ms during VF, p<0.001). While PCO400 tended to increase Smax of APDR at the concentration of 1 micrometer (0.6 to 0.7 by S1S2, 2.3 to 3.0 during VF), it reduced Smax at higher concentrations (-0.01 by S1-S2, p<0.05;-1.1 during VF, p<0.01). The increment of PCO400 concentration was associated with facilitated VT/VF induction (24.4% to 100%, p<0.001). Spontaneous VF induction rate was the highest at 1 micrometer (38.5%) which resulted in the highest Smax. CONCLUSION: PCO400 shows pro-fibrillatory effect by APD reduction and dynamic changes of Smax, Smax is closely related to spontancous induction of VT/VF, and APD90 shortening below 70 ms is critical for the maintenance of VT/VF.
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Action Potentials , Arrhythmias, Cardiac , Heart Ventricles , Kinetics , Membrane Potentials , Microelectrodes , Swine , Tachycardia, Ventricular , Thymidine Monophosphate , Ventricular Premature ComplexesABSTRACT
PURPOSE: Cisapride(Prepulsid(R)) has been recently associated with long QT syndrome. It has been reported to cause Torsades de Pointes and induce early afterdepolarization in rabbit Purkinje fibers. We investigated the electrophysiological effects of cisapride on cardiac action potential duration and ATP-sensitive K channel in papillary muscles. METHODS: Cardiac action potentials in guinea pig papillary muscle were recorded with microelectrodes by electrical stimulation. The concentration and time dependent effects of cisapride on the ventricular muscle were studied. The effects of cisapride were evaluated in the presence of potassium channel blockers. The effect of cisapride in isolated single ventricular myocyte was also evaluated. RESULTS: Cisapride lengthened the action potential duration(APD). The lengthening depended on doses of cisapride and exposure time. The APD prolongation was attenuated by glibenclamide pretreatment, not tetraethylammonium. Cisapride inhibits pinacidil-induced KATP channel activity dose dependently in cell-attached membrane patch. APD prolongation in Purkinje fibers was more prominent than these in the ventricular muscle. CONCLUSION: These results suggest that cisapride lengthens APD in ventricular muscle and that cisapride-induced APD prolongation may be partially linked with KATP channel inhibition.
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Animals , Action Potentials , Arrhythmias, Cardiac , Cisapride , Electric Stimulation , Glyburide , Guinea Pigs , Guinea , Long QT Syndrome , Membranes , Microelectrodes , Muscle Cells , Muscles , Papillary Muscles , Potassium Channel Blockers , Potassium Channels , Purkinje Fibers , Tetraethylammonium , Torsades de PointesABSTRACT
Objective To investigate the changes of action potential duration (APD) and transient outward K + current (I to) and inward rectifier K + current(I K1) of ventricular myocytes after 3 weeks of myocardial infarction, and to inquire into the effect of bisoprolol. Methods APD was recorded with microelectrode. Ventricular myocytes were singly isolated from rabbit heart using modified Langendoff perfusion and soaked with collagenase. I to and I K1 of single rabbit ventricular myocytes were recorded by whole-cell path-clamp technique. Results Both APD 50 and APD 90 of the cell from noninfarcted region in MI group were markedly longer than that in sham group (P