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To observe the effects of hypothermia on the repolarization duration and the expression of Kir2.1 protein of ventricular myocytes in isolated rat heart and explore the role of Kir2.1 protein. Eighteen healthy adult male Sprague-Dawley rats were randomly divided into three groups (n=6 per group): Control group (C group), 35℃ group (H group), 32℃ group (H group). Langendorff isolated heart models were established. After 15 min 37℃ K-H fluid banlanced perfusion, C group continued to perfuse the K-H solution at 37℃ for 30 minutes, H group continued to perfuse the K-H solution at 35℃ for 30 minutes, H group continued to perfuse the K-H solution at 32℃ for 30 minutes. At 15 min of balanced perfusion (T), and 30 min of continuous perfusion (T), the heart rate,and the MAP in the three layers of the left ventricular anterior wall were recorded, the action potential duration at 50% repolarization (MAPD), the action potential duration at 90% repolarization (MAPD) and transmural dispersion of repolarization(TDR) were calculated. At the same time, the occurrence of arrhythmia was recorded. The expression of Kir2.1 protein was measured by Western blot. The average optical density (AOD) and the distribution of Kir2.1 protein were measured by immunohistochemistry in the ventricular tissue measured by electrophysiology. Compared with T, the heart rate was decreased, MAPD and MAPD were prolonged significantly (P＜0.05), and TDR was increased significantly (P＜0.05) in H group, H group at T. Compared with C group, the HR was decreased, the MAPD was prolonged significantly (P＜0.05), TDR was increased significantly (P＜0.05),the expression and the AOD of Kir2.1 protein were decreased significantly (P＜0.05) in Hgroup, Hgroup at T. Compared with H group, the heart rate of H group was decreased significantly (P＜0.05), MAPD and MAPD were prolonged significantly (P＜0.05), and TDR was increased significantly (P＜0.05) at T. The distribution of Kir2.1 protein in group C was normal, while the distribution of Kir2.1 in H group and H group was disordered. Hypothermia prolonged the ventricular duration of repolarization and increased the dispersion of repolarization. The mechanism is related to the down-regulation the expression of Kir2.1 protein and the disorder of the distribution of Kir2.1 protein.
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OBJECTIVES@#To investigate the effect of taurine magnesium coordination compound (TMCC) on torsades de pointes (TdP) in isolated guinea pig hearts.@*METHODS@#Healthy male guinea pigs weighting 250~300 g were randomly divided into 4 groups:①TdP model group (=7):Isolated hearts were perfused by normal K-H solution 20 minutes, then perfused by slowly activated delayed rectifier potassium current(IKs) blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) to establish TdP model;②~④ TdP model + TMCC group (=6):Isolated hearts were perfused by normal K-H solution for 20 minutes, then perfused by IKs blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) for 60 minutes, at the same time TMCC which concentration was 1, 2, 4 mmol/L was administered respectively by Langendorff retrograde aortic perfusion method. Cardiac surface electrocardiogram of guinea pigs was collected and recorded by Biopac electrophysiological recorder. Incidence of TdP, transmural dispersion of repolarization (TDR), instability of QT interval were acquired from Lead Ⅱ electrocardiograph (ECG) wave forms to describe the effect of TMCC on TdP model. Datas were acquired at the time of 20 min and pre-TdP, in case there was no TdP observed, a value of 60 min was entered for calculation purpose.@*RESULTS@#Incidence of TdP in TdP model group was 6/7. TdP incidence could be decreased significantly by 1, 2, 4 mmol/L TMCC, and was 5/6, 1/6, 0/6 respectively. Compared with the pre-drug, Chromanol 293B under hypokalemic solution in TdP model group increased TDR(corrected) evidently(0.05). Compared with the TdP model group, 2, 4 mmol/L TMCC could evidently decrease the instability of QT interval induced by Chromanol 293B under hypokalemic solution(<0.05). During the establishment of TdP model, P waves in more than one cardiac cycle continuously were disappeared in ECG. However, P wave could always be seen independent in ECG acquired from TdP model + TMCC group.@*CONCLUSIONS@#TMCC can play the role against TdP through decreasing TDR and instability of QT interval, and inhibiting early after depolarization(EAD).
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Animals , Male , Anti-Arrhythmia Agents , Pharmacology , Electrocardiography , Guinea Pigs , In Vitro Techniques , Long QT Syndrome , Magnesium , Pharmacology , Random Allocation , Taurine , Pharmacology , Torsades de Pointes , Drug TherapyABSTRACT
Aim To investigate the effect of taurine-magnesium coordination compound (TMCC) on elec-trocardiogram of isolated guinea pig hearts, hoping to describe a primary research on its characteristic of anti-short QT syndrome. Methods The isolated guinea pig heart was retrograde perfused using Langendorff tech-nique. In order to determine the effects of TMCC on QT interval, transmural dispersion of repolarization, effective refractory period, instability of RR interval and instability of QT interval in the presence of potassi-um channel opener pinacidil, the electrocardiogram of isolated guinea pig hearts was recorded using Biopac physiological recorder. Results The shortened QT in-terval and the effective refractory period induced by pinacidil could be prolonged by TMCC; the increased transmural dispersion of repolarization induced by pinacidil could be decreased by TMCC; the increased instability of RR and QT interval induced by pinacidil could be decreased by TMCC. Conclusion TMCC has the effects of anti-SQT2 by prolonging the QT inter-val and the effective refractory period, reducing the transmural dispersion of repolarization and instability.
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Objective To investigate the effect of dexmedetomidine on myocardial repolarization heterogeneity and the expression of Cx43 during ischemia-reperfusion and the role of Cx43 in the dexmedetomidine for inhibition of myocardial repolarization heterogeneity during ischemia-reperfusion in isolated rabbit hearts.Methods Eighteen healthy adult rabbits,weighing (2.0±0.5) kg,were randomly divided into three groups after Langendorff isolated heart perfusion model had been prepared and K-H fluid had been perfused and balanced 15 min.In the control group (group C),37℃ K-H fluid was continuously perfused and balanced for 150 min.In group IR,K-H fluid was stopped after perfusion continue filling for 15 min,and then made the cardiac stop for 60 min with the injection of Thomas solution 10 ml/kg while the heart was protected by the 4℃ Thomas solution around.Following the reperfusion of 4℃ Thomas solution 5 ml/kg was performed for 30 min and the heart was resuscitated by the perfusion of K-H fluid for 60 min.In dexmedetomidine group given (group DEX),dexmedetomidine was added in the K-H fluid and the Thomas solution 25 ng/ml.The other procedures were the same as those of group IR.The heart rate (HR),90% monophasic action potential duration (MAPD90) were recorded at the time of balance perfusion record 15 min (T0),continue perfusion 15 min/balance 30 min (T1),reperfusion 30 min/balance 120 min (T2) and reperfusion 60min/balance 150 min (T3).The transmural dispersion of repolarization (TDR) was calculated.To observe the cardiac reperfusion arrhythmia and rebeating time and recording.Detection expression of Cx43 in the left ventricular myocardial by Western blot and immunohistochemistry at T3.Results Group DEX cardiac resuscitation time was significantly shorter than that of group IR (P<0.05).In group DEX.Compared with T0,HR was significantly decreased and TDR was significantly increased in groups IR and DEX at T2、T3 (P<0.05).Compared with group IR,the TDR of group DEX was significantly decreased at T2、T3 (P<0.05).Compared with group C,the expression of Cx43 was decreased (P<0.05) and the distribution was not uniform in groups IR and DEX.Compared with group IR,the expression of Cx43 was decreased (P<0.05) and the distribution was improved in group DEX.Conclusion Dexmedetomidine could inhibits myocardial repolarization heterogeneity of ischemia-reperfusion injury,and thus play a stable cardiac conduction,reduce reperfusion arrhythmias,and its mechanism may be that dexmedetomidine could inhibits gap junctional uncoupling and inhibits expression and distribution of connexins decreased.
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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 study the effects of dexmedetomidine on the monophasic action po-tential duration and the transmural dispersion of repolarization during ischemia-reperfusion of isolated rabbit hearts and thus explore its effect on myocardial ischemia-reperfusion electrophysiological char-acteristics.Methods Eighteen healthy adult rabbits,weighing (2.0±0.5)kg,were randomly divided into 3 groups after successful preparation of Langendorff isolated heart perfusion model and 1 5 min perfusion and balance of K-H fluid.In the control group (group C),37 ℃ K-H fluid was continuously perfused and balanced for 1 50 min.In the ischemia/reperfusion group (group IR),K-H fluid was stopped after continuous perfusion and balance for 1 5 min and cardiac arrest was induced for 60 min with the injection of Thomas solution (4 ℃,10 ml/kg)while the heart was protected by the low tem-perature Thomas solution (4 ℃)around it.Reperfusion of Thomas solution (4 ℃,5 ml/kg)was performed for 30 min and the heart was resuscitated by the perfusion of K-H fluid for 60 min.In dexmedetomidine group (group DEX),dexmedetomidine (25 ng/ml)was added in the K-H fluid and the Thomas solution.Other procedures were same as in group IR.Heart rate(HR),monophasic ac-tion potential amplitude (MAPA)of the three layers of heart [endocardium (Endo),myocardium (Mid)and epicardium (Epi)],0 phase maximal increase rate (Vmax),90% monophasic action po-tential duration (MAPD90 )and transmural dispersion of repolarization (TDR)were recorded at the time of continuous balance perfusion 1 5 min(T0 ),continuous perfusion 1 5 min/balance 30 min(T1 ), reperfusion 30 min/balance 120 min(T2 )and reperfusion 60 min/balance 1 50 min(T3 ).Cardiac ar-rhythmia and resuscitation time at cardiac reperfusion were observed,without using drugs to restore normal cardiac rhythm.Results In group DEX,cardiac resuscitation time was significantly shorter (1 6.67±3.78)s than that in group IR (46.33±7.29)s (P <0.05);At T2 ,in group IR,arrhythmia was seen in 6 rabbits and normal cardiac rhythm was restored within 2 min in two rabbits,while in group DEX,arrhythmia was seen in 2 rabbits and normal cardiac rhythm was restored within 2 min in one rabbit,without the use of any drugs.When compared with T0 ,HR was slower at T2 and T3 in group IR and at T1-T3 in group DEX (P <0.05);Compared with T1 ,HR was slower at T2 and T3 in group DEX (P <0.05);Compared with T2 and group C,HR was slower at T3 in group DEX;At T1-T3 ,HR in group DEX were significantly slower than that in group IR (P <0.05).Compared with T0 ,MAPD90 of Mid at T1 and Epi,Mid,Endo at T2 and T3 in group DEX were significantly extend-ed (P <0.05);Compared with T1 ,MAPD90 of Epi,Mid,Endo in group DEX were significantly ex-tended at T3 ;MAPD90 of Mid in group DEX was significantly longer than that in group C at T3 (P <0.05);At T2 and T3 ,MAPD90 of Epi,Mid,Endo in group DEX were longer than that in group IR (P <0.05).Compared with T0 and group C,TDR at T2 and T3 in group IR and at T1-T3 in group DEX significantly increased (P <0.05),while TDR in group DEX were less than that in group IR at T2 and T3 (P <0.05).Conclusion Dexmedetomidine appeared to prolong MAPD and restrain the dis-proportion of resuscitation of myocardial ischemia-reperfusion injury.Dexmedetomidine could have the effect of stabilizing myocardial ischemia-reperfusion electrophysiological characteristics.
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AIM:To study the effect of remifentanil on monophasic action potential and transmural dispersion of repolarization (TDR) in the 3-layer myocardium of isolated rabbit hearts .METHODS:Adult rabbits (n=18, 2.0 ~2.5 kg) were used to isolate the hearts for preparing Langendorff perfusion model .The hearts were randomly divided into 3 groups after perfusion with K-H solution for 15 min: the perfusion in control group ( C group ) continued for 60 min; the hearts in remifentanil group ( R group ) were perfused with 12 μg/L remifentanil K-H solution for 60 min; the hearts in remifentanil+aminophylline group ( RA group ) were given 60-min perfusion of 12 μg/L K-H remifentanil +30 mg/L aminophylline .The HR and 3 layers of myocardial monophasic action potential ( MAP) in the left ventricular anterior wall were recorded at time points after balanced infusion for 15 min ( T0 ) , and continued perfusion for 15 min ( T1 ) , 30 min ( T2 ) and 60 min ( T3 ) .The monophasic action potential duration of repolarization at 90%( MAPD90 ) and the transmural dispersion of repolarization (TDR) were calculated.The early afterdepolarization, delay afterdepolarization and arrhythmia were also observed.RESULTS:In R group, slower HR and prolonger MAPD90 and TDR at T1 ~T3 were observed as com-pared with those at T0(P<0.05).R group showed slower HR and longer MAPD 90 and TDR than C group and RA group (P<0.05).CONCLUSION:Remifentanil slows the HR, extends the MAPD90 and increases the TDR, thus being prone to induce reentry.Aminophylline makes HR faster and MAPD90 shorter, thereby reducing the TDR.
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Objective To investigate the effects of ibutilide and amiodarone on the ventricular transmural heteroge-neity of repolarization and ventricular arrhythmia for the treatment of atrial fibrillation. Methods Eighty-seven patients with paroxymal atrial fibrillation at 48 h~7 d were enrolled and randomized to two groups, ibutilide and amiodarone treat-ment groups. The successful rate of cardioversion to sinus rhythm was compared between two groups. The electrocardiograph-ic QT interval and Tpeak-end/QT ratio were also analyzed before and after treatment in two groups. Results The successful rate of cardioversion was significantly higher in ibutilide group than that of amiodarone group (61.7%vs 40.7%, P＜0.05). The QT intervals and Tpeak-end/QT ratio were both significantly increased in ibutilide group (P＜0.05), which were re-turned to the levels before treatment in 2 hours and 1 hour, respectively (P＜0.05). The QT intervals were significantly in-creased in the amiodarone group (P＜0.01), which were continued until 4 h after treatment. There were no significant differ-ences in the Tpeak-end/QT ratios before and after treatment (P>0.05). Conclusion The successful rate of cardioversion to sinus rhythm for atrial fibrillation by ibutilide was significantly higher compared with that of amiodarone. Ibutilide slightly in-creased the transmural heterogeneity of repolarization within the first hour, which may increase the risk of ventricular arrhyth-mia.
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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 investigate the effect of positive acceleration (+Gz) on monophasic action potential duration of 90%repolarization( MAPD90 ) and transmural dispersion of repolarization ( TDR) in ventricles of rabbits and to explore the cellular electrophysiologic mechanism of tachyarrhythmia induced by positive acceleration .Methods Twenty-four healthy, male New Zealand white rabbits were randomly and equally divided into control group and +Gz group.The +Gz group rabbits were given +8 Gz exposure, 1 min a time, 3 times a day,and a total of 7 days.The two groups were subjec-ted to Holter monitoring at the same time to observe the incidence of tachyarrhythmia .Using the monophasic action potential ( MAP) recording technology , the MAP of the left ventricle was recorded while MAPD 90 and TDR were measured .By using Burst stimulation method , the right ventricular anterior wall of the rabbits was stimulated , and the incidence of tachya-rrhythmia was observed .Results The Holter record showed that the incidence of tachyarrhythmias in +Gz group was 55%(6/11), but the control group did not have any case of tachyarrhythmias .Compared with the control group ,MAPD90 of en-docardial and epicardial cells was significantly decreased in the +Gz group, while MAPD90 of middle myocardial cells did not change significantly ,but TDR was increased obviously .Four rabbits in +Gz group suffered from tachyarrhythmias dur-ing Burst stimulation ,and the incidence of tachyarrhythmias was 40% ( 4/10 ) .Conclusion +Gz exposure can increase the incidence of tachyarrhythmias .The shortened MAPD90 of ventricular muscle cells and the increased TDR may be the cell electrophysiological mechanisms of tachyarrhythmias induced by +Gz.
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Objective: Cardiac resynchronization therapy defibrillator (CRT-D) increases ventricular transmural dispersion of repolarization (TDR). Our work evaluated the relationship between QTc interval of TDR indicators, TpTe, TpTe/QTc ratio and rapid ventricular arrhythmia in patients with CRT-D. Methods: A total of 160 consecutive patients who received CRT-D implantation in our hospital from 2011-01 to 2013-03 were studied. The immediate post operative ECG was collected to analyze lead V5 QTc interval, TpTe and TpTe/QTc ratio for assessing its TDR. The patients were divided into 2 groups: Treatment group, the patients with ventricular tachycardia or ventricular ifbrillation received CRT-D,n=30 (18.7%) and Non-treatments group,n=130 (81.3%). All patients were followed-up for (20 ± 10) months and the rapid ventricular arrhythmia was recorded by CRT-D devices. Results: The patients in Treatment group had increased TpTe/QTc (0.24 ± 0.05) vs (0.20 ± 0.04, and TpTe (119 ± 30) ms vs (95 ± 20) ms, bothP<0.001. The QTc interval was similar between 2 groups (480 ± 60) ms vs (470 ± 70) ms,P=0.6 and QTc interval was not related to the risk of CRT-D requirement. The sensitivity and speciifcity for TpTe/QTc ≥ 0.25 predicting the risk of ventricular arrhythmia in CRT-D patients were at 47% and 91%, while TpTe ≥ 120 ms were at 40% and 95%respectively. The post CRT-D surviving curve analysis indicated that TpTe/QTc ratio and TpTe could predict the prognosis in relevant patients,P<0.001. Conclusion: The elevated TpTe and TpTe/QT ratio may increase the incidence of CRT-D requirement in patients with ventricular arrhythmia after resynchronization.
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Objective To investigate the relationship of T peak-T end (Tp-Te) interval and Tp-Te interval disper-sion (Tp-Ted) in different periods of myocardial ischemia in patients with acute myocardial infarction (AMI), and to assess the clinical significance of Tp-Te and Tp-Ted for prediction of the ventricular arrhythmia (VA). Methods A total of 80 pa-tients with AMI were enrolled in the study. The sizes and changes of Tp-Te and Tp-Ted were observed during the acute phase and recovery phase in patients. The differences of Tp-Te and Tp-Ted were compared between ventricular tachycardia group (A group), ventricular premature beats group (B group) and non- ventricular arrhythmia group (C group). Results The values of Tp-Te and Tp-Ted were obviously longer in acute period [(125.22±17.70) ms and (54.76±13.26) ms] than those in recovery period[ (113.84±17.37) ms and (42.06±13.95)ms] (P<0.01). The values of Tp-Te and Tp-Ted were signifi-cantly longer in A group[ (134.82±19.56) ms and (62.00±15.19) ms] than those in B [(122.94±15.09) ms and (54.09±10.56) ms ]and C group [(110.09±15.21) ms and (45.27±9.85) ms]. The values were higher in B group than those of C group. Con-clusion The Tp-Te interval and Tp-Ted prolongated in acute phase than those of recovery phase in patients with AMI. Tp-Te interval and Tp-Ted can be used as an important index to predict VA in patients with AMI.
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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.
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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.
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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.
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The effects of amiodarone on transmural dispersion of ventricular effective refractory periods (ERPs) in the normal and hypertrophic canine heart were investigated in vivo. By using the programmed stimulation protocol, the ERPs of epicardium (Epi), midmyocardium (Mid) and endocardium (Endo) were measured by inserting specially-designed electrodes into the three myocardial layers before and after mainlining of amiodarone. No significant ERPs-dispersion was observed in the three layers before and after mainlining of amiodarone in the normal group. In contrast, ERPs of all the three layers were prolonged in the hypertrophic heart, while the ERPs-dispersion was reduced significantly after mainlining of amiodarone. The ERPs-dispersion was significantly increased in the hypertrophic heart but not in the normal heart using "long-short" and "short-long" interval stimulation technique. It was concluded that (1) the differences in ERPs-dispersion among the three layers were significant in hypertrophic heart, and differences were not significant in normal canine heart;(2) ERPs of each three-myocardial layers were significantly prolonged after using amiodarone, but the ERPs-dispersion decreased in hypertrophic heart and (3) the programmed extrastimulus technique of "long-short" and "short-long" intervals increased the transmural ERPs-dispersion in the hypertrophic heart.
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Objective Toinvestigate the role of dynamic dispersion of electrical recovery in ventricular fibrillation maintenance mechanism.Method Thirty-seren male Yorkshire pigs weighing (23?2.5) kg at 3 months age were randomly divided into Sham-operated group and myocardial infarction group in which the first branch of left anterior descending coronary artery of animals was hgated.After 4 weeks,according to VF occurrence by programmed electrical simulation,the myocardial infarction hearts were divided into two groups, twelve hearts in VF (+) group or six hearts in VF (-) group;and the normal hearts were divided into two groups,five hearts in VF (+) group or ten hearts in VF (-) group.Action potential duration (APD) of subendocardial,subepicardial and mid-layer myocardium of left ventricular anterior wall were recorded simultaneously.The relationship between APD and diastolic interval was quantified as an electrical restitution curve.A Student's-test was used to specify differences between groups.Results At the fourth week after coronary artery ligation,eighteen myocardial infarction hearts and fifteen normal hearts were investigated.When investigating transmural dispersion of reporlarization (TDR) of left ventricle,there was no difference between VF (+) group and VF (-) group [ (20.43?7.01) ms vs (22.32?7.53) ms,P=0.45],although there was statistically significant between normal hearts and myocardial infarction hearts [ (15.66?4.45) ms vs (25.72?6.70) ms,P =0.001].The percentage of APD restitution slope exceed 1 and APD restitution slope maximum were high in the VF (+) group with myocardial infarction hearts and in the VF (+) group with normal hearts, lower in the the VF (-) with normal hearts and lowest in the the VF (-) group with myocardial infarction hearts.Conclusion Dynamic APD restitution properties may play an important role in the ventricular fibrillation maintenance mechanism.The APD restitution slope and not static TDR have prognostic value regarding ventricular fibrillation events.The hearts with the steepest of APD restitution curves has the greatest liability of ventricular fibrillation to happen.
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@#ObjectiveTo investigate the effects of imidapril on the transmural dispersion of repolarization of the noninfarcted myocardium of rabbits after myocardial infarction. MethodsRabbits with left coronary artery ligation were prepared and allowed to recover for 8 weeks. Monophasic action potentials of three layers myocardium in the noninfarcted myocardium in vivo were recorded. Myocytes were isolated from subendocardial, midmyocardial and subepicardial regions of the noninfarcted left ventricular wall and action potentials were recorded using whole-cell patch clamp technique. ResultsCompared with sham group, the monophasic action potential duration (MAPD90) of three layers myocardium were all prolonged. Prolongation of MAPD_ 90 of midmyocardial cell was the most striking and ventricular fibrillation threshold (VFT) was decreased. After treatment with imidapril, the transmural dispersion of repolarization (TDR) decreased and the VFT enhanced. ConclusionImidapril reduced the transmural dispersion of repolarization of noninfarcted area in rabbits after myocardial infarction, which may contribute to its antiarrhythmic efficacy.
ABSTRACT
To study the effect of of lidocaine and amiodarone on the transmural heterogeneity of ventricular repolarization in isolated rabbit hearts model of sustained global ischemia and to explore the mechanisms underlying the antiarrhythmic activity of lidocaine and amiodarone, rabbits were randomly divided into 4 groups: control group, ischemia group, lidocaine group and amiodarone group. By the monophasic action potential (MAP) recording technique, MAPs of recorded across the left ventricular free wall in rabbit hearts perfused transmural dispersion of repolarization (TDR) and arrhythmic induced by ischemia. Our results showed that TDR of three myocardial layers in ischemia group were significantly lengthened after ischemia. TDR was increased from 17.5±3.9 ms to 31.2±4.6 ms at the time that concided with the onset of sustained ventricle arrhythmic. Amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia, and no significant difference was found at other ischemia time points. 5 cases had ventriclar arrhythmia in ischemia group (62.5 %), but no case in lidocaine group (P<0.01) and only 1 case in amiodarone group had ventrilar arrhythmia (P< 0.01). No significant difference was found between amiodarone group and lidocaine group. It is concluded that TDR of of three myocardial layers increases significantly at ischemia and it is closely associated with development of ventricular arrhythmia, and amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia and has no effects at other ischemia time points.
ABSTRACT
The effect of acute ischemia on the electrophysiological characteristics of the three layers myocardium of canine in vivo was investigated. Twelve canines were divided into two groups randomly: acute ischemia (AI) group and sham operation (SO) group. By using the monophasic action potential (MAP) technique, MAP and effective refractory period (ERP) of thethree layers myocar dium were measured by specially designed plunge needle electrodes and the transmural dispersion of repolarization (TDR) and transmural dispersion of ERP (TDE) were analyzed. The results showed that in the AI group, MAP duration (MAPD) was shortened from 201.67±21.42 ms to 169.50±13.81 ms (P＜0.05), but ERP prolonged to varying degrees and TDE increased during ischemia.In the SO group, MAPD and ERP did not change almost. Among of the three layers myocardium of canine, MAPD was coincident in two groups. It was concluded that during acute ischemia, MAPD was shortened sharply, but there was no significant difference among of the three layers myocardium. The prolonged ERP was concomitant with increased TDE during acute ischemia, which may play an important role in the occurrence of arrhythmias induced by acute ischemia. These findings may have important implications in arrhythmogenesis.