Effect of the right ventricular isolation procedure on ventricular vulnerability to fibrillation

A certain critical mass of myocardium is believed to be necessary to initiate ventricular fibrillation. The right ventricular isolation procedure, employed clinically to confine ventricular tachyarrhythmias to the right ventricle, decreases the ventricular mass available for fibrillation by isolating the ventricles from each other. The effect of this procedure on ventricular fibrillation thresholds is unknown. Left and right ventricular fibrillation thresholds were measured before and after right ventricular isolation in 10 adult mongrel dogs utilizing a single 5 ms stimulus of increasing current strength applied to the epicardium during the vulnerable period. There were no significant differences in heart rate, aortic blood pressure, left atrial pressure, temperature, arterial blood gases or regional myocardial blood flow between the study periods. In 9 of the 10 dogs, the isolated right ventricle could not sustain ventricular fibrillation despite the utilization of stimulus strengths of up to 80 mA. In the 10th dog, the right ventricular fibrillation threshold increased 150%, from 20 to 50 mA. The left ventricular fibrillation threshold markedly increased in every dog, with an average increase from 23 +/- 2 to 40 +/- 4 mA (p less than 0.0005). To determine whether time, cardiopulmonary bypass or the right ventricular incision could cause similar changes in ventricular fibrillation threshold, five different dogs underwent the entire experimental protocol except for incomplete isolation of the right ventricle. There were no significant changes in ventricular fibrillation thresholds in these dogs. Thus, in the canine model, right ventricular isolation can prevent the occurrence of sustained fibrillation in the isolated right ventricle and can significantly increase the left ventricular fibrillation threshold.     

A model of chronic ischemic arrhythmias: The relation between electrically inducible ventricular tachycardia,ventricular fibrillation threshold and myocardial infarct size

To study the relation between inducible ventricular tachycardia and ventricular vulnerability, myocardial infarction was created in 22 closed chest mongrel dogs by inflating a balloon catheter in the left anterior descending coronary artery for 2 hours. The presence of inducible ventricular tachycardia was determined by programmed electrical stimulation of the right ventricle in each dog before and 4 days after infarction, using a transvenous electrode catheter and a “clinical” stimulation protocol. In each dog the repetitive ventricular response threshold and the ventricular fibrillation threshold were measured before and 4 days after infarction.Ventricular tachycardia was not inducible in any dog before infarction. After infarction, sustained ventricular tachycardia was inducible in 10 (45 percent) of 22 dogs and nonsustained tachycardia in an additional 4 dogs (18 percent). Ventricular fibrillation threshold was greatly reduced 4 days after infarction in dogs with inducible sustained tachycardia (mean ± standard deviation 29 ± 11 to 10 ± 5 mA, p < 0.001); the mean threshold did not change significantly in dogs without inducible sustained tachycardia. Both the ventricular fibrillation threshold and mean ventricular repetitive response threshold were reduced in the dogs with sustained ventricular tachycardia; neither was significantly altered in the dogs without sustained tachycardia. The magnitude of change in the two thresholds frequently differed; hence, a correlation was weak between the control and postinfarction repetitive response/fibrillation threshold ratio (r = 0.41). Postmortem measurement of infarct size demonstrated an association between this measurement and the presence of inducible ventricular tachycardia. Sustained ventricular tachycardia was not inducible in the presence of a small infarct.It is concluded that: (1) Inducible ventricular tachycardia on the 4th day after myocardial infarction is associated with a considerable decrease in the ventricular fibrillation threshold; (2) changes in the repetitive response and fibrillation thresholds after myocardial infarction may not be parallel, complicating the use of the repetitive ventricular response threshold as a substitute for the ventricular fibrillation threshold in the postinfarction state; (3) a large infarct predisposes the heart to electrically inducible sustained ventricular tachycardia.     

The effect of chemical ablation of the endocardium on ventricular fibrillation threshold

The purpose of this study was to examine the effects of ablation of the superficial endocardium and Purkinje network on left ventricular fibrillation threshold. Lugol's solution was applied through small ventriculotomies to the left and right ventricular endocardium of 10 dogs on cardiopulmonary bypass. Two control groups of five animals each underwent either endocardial application of saline or epicardial application of Lugol's solution. Ventricular fibrillation threshold was measured before and after each intervention by the single-stimulus technique. Application of Lugol's solution to the endocardium resulted in a 102 +/- 15% increase in ventricular fibrillation threshold from a control value of 26 +/- 2 to 53 +/- 6 mA (p less than .005). In two animals, ventricular fibrillation could not be initiated postoperatively. In the control groups, there were no significant changes in ventricular fibrillation threshold. Histologic examination revealed that Lugol's solution obliterated less than 0.5 mm of superficial endocardium while sparing the adjacent myocardium. Electrophysiologic and rheologic data confirmed the discrete nature of the chemical injury. Thus ablation of the superficial ventricular endocardium with Lugol's solution results in a profound increase in the ventricular fibrillation threshold with only minimal tissue destruction.     

双心室起搏埋藏式心脏转复除颤器的安置

评价一次性置入双心室起搏埋藏式心律转复除颤器 (双腔ICD)的安全性和有效性。5例冠心病冠状动脉搭桥术后的患者 ,伴有严重的慢性充血性心力衰竭和恶性室性心律失常 ,置入双腔ICD。结果 :5例左室电极导管和双腔ICD均一次成功置入 ,左室电极放入冠状静脉的侧后枝 ,急性起搏阈值 0 .8± 0 .6V ,电阻 72 2± 12 8Ω ,R波振幅18.6± 5 .3mV ,电流 1.6± 0 .5mA ,而双心室起搏时其起搏电极参数均优于左室电极 ,除颤阈值≤ 14J。结论 :对伴严重慢性充血性心力衰竭和恶性室性心律失常的患者 ,置入双腔ICD是安全、易行的。     

Ischemic ventricular fibrillation: The importance of being spontaneous

Although the energy level required to defibrillate normal myocardium is low and constant, as determined from studies of induced ventricular fibrillation, little is known of the specific energy requirements in regionally ischemic hearts for spontaneous or induced ventricular fibrillation. In this study the lowest energy threshold for defibrillation was determined in 10 open chest dogs with reversible 10 minute coronary occlusions at various sites for each of 44 events of ventricular fibrillation, using apical and superior vena caval electrodes with a generator providing variable output of 1 to 30 watt seconds. The ischemic mass, quantitated from postmortem angiographic and planimetric data, was 52 ± 9 percent (mean ± standard deviation) of the left ventricle in dogs with induced ventricular fibrillation (Group I), 52 ± 12 percent in dogs with spontaneous ventricular fibrillation after occlusion (Group II) and 54 ± 9 percent in dogs with spontaneous ventricular fibrillation after reperfusion (Group III). Defibrillation thresholds in watt seconds were 9 ± 7 in Group I (n = 12), 19 ± 10 in Group II (n = 13) and 18 ± 10 in Group III (n = 19). (Group I versus Groups II and III, probability [p]<0.025). In nonischemic hearts, the defibrillation threshold was 3 ± 2 (n = 32) (p <0.001 compared with values in Group I, II or III). Thus, despite similar masses of ischemia, twice as much energy was required for defibrillation of spontaneous ventricular fibrillation (whether after occlusion or reperfusion) as for induced ventricular fibrillation, suggesting that these conditions are caused by different metabolic or pathologic derangements. Such differences should be considered in assessing interventions such as drug therapy designed to inhibit the repetitive ventricular response and in design of implantable defibrillators.     

快速右室起搏致充血性心力衰竭犬心室复极离散性的变化

目的研究快速右室起搏致充血性心力衰竭(CHF)犬心室复极离散性的变化。方法25只犬随机分成两组:对照组(n=10)及CHF组(n=15)。应用快速右室起搏(240次/分,共4～5周)制作CHF犬模型,应用心脏电刺激技术测定心电生理参数。结果与对照组比较,CHF组左右室的心室兴奋恢复时间(VRT)均明显延长(P<0.01),心尖部的VRT延长更明显(P<0.05),VRT离散性(DVRT)明显增加(32±6msvs13±4ms,P<0.01);左室三层心肌VRT均明显延长(P<0.01),中层心肌的VRT延长更明显(P<0.05),跨室壁DVRT(TDVRT)明显增加(44±8msvs19±5ms,P<0.01);CHF组心室颤动阈值(VFT)明显降低(11±3mAvs34±7mA,P<0.01)。结论CHF犬DVRT及TDVRT明显增大,使心室复极不均一,易致折返活动,同时VFT降低。     

Estimated global transmural distribution of activation rate and conduction block during porcine and canine ventricular fibrillation

We quantified ventricular fibrillation (VF) activation rate, conduction block, and organization transmurally in pigs and dogs, whose transmural Purkinje distribution differ. In six pigs and five dogs, 75 to 100 plunge needles, containing four electrodes for the right ventricle (RV) and six electrodes for the left ventricle (LV) and septum, were inserted in vivo. Six VF episodes were electrically initiated and allowed to last for 47 to 180 seconds. From the FFT power spectra, dominant frequency (DF), an estimate of activation rate, and incidence of double peaks (DPI), an estimate of conduction block, were calculated every 8 ms at each electrode. DF was highest at the epicardium and lowest at the endocardium, whereas DPI was highest at the endocardium and lowest at the epicardium for the entire LV and the RV base in both pigs and dogs for the first 70 seconds of VF. This distribution changed little throughout the first 3 minutes of VF in pigs but reversed in dogs by 2 minutes of VF. In conclusion, estimated activation rates and conduction block incidence during VF are not uniformly distributed transmurally. During the first minute of VF, the faster activating LV base epicardium exhibits less estimated block than the slower endocardium, raising the possibility that faster activating epicardium generates wavefronts that drive the endocardium early during VF. Constancy of this pattern in pigs but its reversal by 2 minutes in dogs is consistent with the hypothesis that activation during later VF is driven by Purkinje fibers.     

Determining the Safety of Radiofrequency Ablation in Cardiovascular Implantable Electronic Devices

Radiofrequency catheter ablation (RFCA) is an effective treatment for arrhythmias. The effects of RFCA on cardiovascular implantable electronic devices (CIED) function have varied. We aim to study the effect of RFCA on device parameters and clinical outcomes in patients with CIED. We conducted a single-center retrospective cohort study between 2011 and 2018. Generator and lead parameters were compared pre- and post-ablation using paired sample t-test. The median follow-up interval for documentation of procedure-related complications and clinical outcomes was 8 weeks. We identified 119 eligible patients; whose mean age was 64.5 ± 11.91 years and 22 (18.4%) were females. Types of CIED include single-chamber implantable cardioverter defibrillators (8.93%), dual-chamber implantable cardioverter defibrillators (41.96%), and either dual-chamber or biventricular pacemakers (44.54%). Arrhythmias for which patients underwent RFCA include atrial fibrillation/atrial tachycardia (15.22%), atrial flutter (38.14%), atrioventricular node reentrant tachycardia (13.56%), and premature ventricular complex or ventricular tachycardia (20.34%). No statistically significant difference was observed in pre- and post-ablation: (1) atrial sensing thresholds, pacing thresholds, lead impedance; (2) right ventricle sensing and pacing thresholds; and (3) left ventricle pacing threshold and impedance. A decrease in right ventricle impedance after ablation (549.77 ± 173 ohm vs 507.40 ± 129.0 ohm, P-value <0.004) was observed. Zero complications or deaths were observed. In this single-center study, RFCA did not significantly impact CIED function and was not associated with short-term complications. However longer follow-up is required to confirm these findings.     

Termination of ventricular fibrillation in dogs by depolarizing a critical amount of myocardium.

The role of a critical myocardial mass required to maintain ventricular fibrillation initiated by rapid ventricular pacing was studied by two methods in dogs placed on total cardiopulmonary bypass. In the first method, depolarization of a limited myocardial mass was accomplished by injecting potassium chloride into one or two coronary arteries. Injection of potassium chloride simultaneously into the left circumflex and left anterior descending coronary arteries abolished ventricular fibrillation more often than did injection into any other single or combination of two coronary arteries (P less than 0.0001). Ventricular fibrillation could not be reinitiated as long as the left ventricle remained inexcitable. Immersing the heart in a solution of potassium chloride or injecting the solution into the right and left ventricular cavities failed to terminate ventricular fibrillation. The second method evaluated the amount of current necessary to terminate ventricular electrodes, between two left ventricular electrodes and between one right ventricular and one left ventricular electrode. Electrical shocks of equal magnitude terminated ventricular fibrillation most often when those shocks were delivered between an electrode located at the right ventricular apex and an electrode located at the posterior base of the left ventricle, and least often when the shock was delivered between two right ventricular electrodes. Successful defribillation results when a critical amount of myocardium becomes depolarized by either potassium chloride or electrical discharge; depolarization of every cell in both ventricle is not necessary to terminate ventricular fibrillation in the entire heart.     

Elevated collagen content in volume overload induced cardiac hypertrophy

This investigation was designed to determine if chronic volume overload is associated with altered collagen content of five regions of the myocardium. Five adult cats were subjected to a 6-week period of chronic volume overload induced by atrial septotomy and five untreated animals served as controls. Significant (P < 0.05) right ventricular hypertrophy was present as indicated by the right ventricular body weight ratio. For control animals this ratio was 0.68 ± 0.04 g/kg; for volume overloaded animals it was 0.83 ± 0.05 g/kg.) The collagen content was assessed by measuring the hydroxyproline content of the dried cardiac muscle. Right ventricular endocardium hydroxyproline in volume overloaded animals was significantly elevated above that in control animals (in the latter it was 5.30 ± 0.36 μg/mg; in the former it was 6.33 ± 0.18 μg/mg) while the epicardial collagen content was unchanged. Similarly, the amount of collagen found in the left ventricle was significantly increased in the endocardium and normal in the epicardium. Septal collagen concentration was unaltered in volume overloaded animals. This study demonstrated that alterations in cardiac muscle collagen concentration are associated with volume overload and that these cellular changes are nonuniform.     

Divergent time courses of ventricular vulnerability of the heart to ventricular tachycardias and ventricular fibrillation in the early necrosis stage of acute experimental myocardial infarct

Early necrosis in acute experimental myocardial infarction is characterized by severe ventricular dysrhythmias beginning approx. 6 hours after coronary artery occlusion and persisting for 2-5 days. It was the aim of this study to investigate the comparative changes in ventricular vulnerability to spontaneous and stimulus-induced tachycardia and fibrillation during early necrosis 6-18 hours following acute coronary artery occlusion. Results: 1) The thresholds for repetitive extrasystoles and for ventricular fibrillation determined via electrodes placed on to the endocardium of the right and left ventricle outside of the ischemic area are within the normal range of the non-ischemic heart. 2) Both stimulation thresholds increase significantly within the area of infarction and in many cases are not inducible any more after 18 hours of ischemia, whatever amount of current is applied. 3) Sustained ventricular tachycardia can be induced in about 30% of cases after an occlusion lasting approx. 6 hours and in about 80% after an occlusion period of 18 hours. 4) Electrically induced ventricular tachycardias differ from spontaneously occurring VT in so far as the former appear to be due to a reentry mechanism, whereas the latter seem to be "accelerated ventricular rhythms" and thus of focal origin. Our results demonstrate that enhanced ventricular vulnerability during early necrosis in acute myocardial infarction is predominantly due to ventricular tachycardia rather than to ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of coronary artery disease on the ventricular fibrillation threshold in man.

The ventricular fibrillation threshold (VFT) was measured in 28 patients at the time of cardiac surgery. The VFT was measured with a 100 Hz train of 24 rectangular pulses positioned across the ST segment and T wave. Current was applied to the epicardial surface of either ventricle with a bipolar electrode probe. In six patients, the normal right VFT was 24.3 +/- 5.2 mA, and in 10 patients the normal left VFT was 33.6 +/- mA (p less than 0.05). In 12 patients with greater than or equal to 75% obstruction of the left anterior descending coronary artery, the left VFT was 18.6 +/- 6.9 mA. This value was significantly less than the left VFT in patients without coronary artery disease (p less than 0.001). This study shows that the VFT can be measured in man and that coronary artery disease reduces this parameter.     

LQT2模型室性心律失常电生理机制研究

为探讨心室肌跨壁复极离散度 (TDR)和心脏兴奋的恢复性质在长QT综合征 (LQTS)室性心律失常发生过程中的作用 ,应用冠状小动脉灌流的兔左室肌楔形组织块标本 ,分模型组和对照组 ,采用浮置玻璃微电极法同步记录心室肌内、外膜心肌细胞动作电位和跨壁心电图。模型组以 30 μmol/L的d sotalol台氏液灌流 ,制备LQT2模型。对照组以标准台氏液灌流。结果 :模型组和对照组比较TDR有显著性差异 (83.6± 14 .0msvs 4 8.6± 5 .3ms,P <0 .0 1,n =10 )。模型组内、外膜动作电位时程 (APD)恢复曲线最大斜率均大于 1,而对照组均小于 1,两组间APD恢复曲线最大斜率比较有显著性差异 (P <0 .0 1,n =2 0 )。模型组在S1S2 程序刺激下尖端扭转型室性心动过速的发生率为70 %。对照组无 1例发生室性心律失常。结论 :心脏兴奋的恢复性质和心室肌TDR均参与了LQT2室性心律失常的发生。     

兔在体左心室肥厚心肌跨室壁复极不均一性的实验研究

目的　探讨兔在体左心室肥厚心肌跨室壁复极不均一性的变化。方法　以腹主动脉缩窄术制备家兔高血压左心室肥厚模型 (腹主动脉缩窄组 ) ,并设假手术组 (仅游离腹主动脉未缩窄 )作为对照。采用自制复合式电极在兔左心室游离壁同步记录在体心内膜、心肌中层、心外膜心肌单相动作电位 (MAP) ,比较两组间跨室壁复极不均一性的差异。结果　腹主动脉缩窄组平均动脉压、左心室游离壁厚度、全心重量及其与体重比率均大于假手术组。缩窄组三层心肌单相动作电位复极至 10 0 %的时程 (MAPD1 0 0 ) (内膜 191± 19ms,中层 2 44± 2 4m s,外膜 196± 15 ms)均比假手术组 (内膜 170± 18ms,中层 172± 15 ms,外膜 168± 16m s)延长 ,以中层心肌 MAPD1 0 0 的延长最为明显 ;缩窄组跨室壁复极离散度 (TDR) (65± 10 ms)较对照组 (4± 3 m s)明显增大 (P<0 .0 1)。结论　兔在体左心室肥厚心肌跨室壁复极不均一性明显增大 ,可能是肥厚心肌心律失常发生增多的原因之一     

缺血性室性心动过速折返机制的实验研究

对１８条缺血性心肌模型犬中发生室性心动过速（简称室速）的６条犬采用组合双极电极记录心肌局部电图，进一步探讨缺血性心脏病室速的机制。结果显示：①缺血区各层心肌电图和心外膜局部电图上均出现延迟电位及碎裂波。②室速的激动顺序为缺血区心内膜（作参照，为０ｍｓ）、缺血区心外膜（１０±０．１０ｍｓ）、边缘区心内膜（１０±０．１２ｍｓ）、边缘区心外膜（１６±０．２０ｍｓ）、正常区心内膜（２０±０．５０ｍｓ）、正常区心外膜为（２７±０．２０ｍｓ）。③当体表ＩＩ导联心电图和心外膜、心肌局部电图均出现心室颤动时，心内膜仍表现为室速的图形。认为室速是多平面多折返所形成的“立体折返”激动的结果；如何寻找折返环入口作为射频消融治疗的靶点至关重要     

应用自制复合电极同步记录兔左心室游离壁三层心肌的单相动作电位

应用自制复合电极同步记录家兔在体三层心肌的单相动作电位 (MAP) ,并与经典的心内膜电极、心外膜吸附电极和三层独立电极记录结果进行比较。结果显示 :①应用自制复合电极同步记录家兔在体的三层心肌MAP形态及时程与经典的记录结果相近 ;②在心动周期 (CL)为 30 0ms时 ,三层心肌的MAP复极达 90 %的时程 (MAPD90 )无显著差异 ,当CL为 80 0ms时 ,家兔心外膜心肌 (Epi)、中层心肌 (M)和心内膜心肌 (Endo)的MAPD90 分别为 2 15± 18,2 6 2± 16 ,2 16± 12ms,M与Epi及Endo相比 ,差异有显著性 (P <0 .0 5 ,n =8) ,跨室壁复极离散度为 34± 3ms。结论 :应用复合电极同步记录在体心肌跨室壁三层MAP是可行的 ,家兔心脏跨室壁心肌电生理在正常心率时无明显差异 ,而当心率减慢时则异质性增加。     

Epicardial activation of the human ventricle: Effects of left ventricular hypertrophy

To determine the effects of left ventricular hypertrophy on eplcardlal activation of the human heart, Intraoperative eplcardlal mapping of 40 to 66 points was performed In 10 patients undergoing aortic valve replacement. Mean calculated left ventricular mass was 364 ± 98 g. All patients had normal left ventricular contraction. Earliest eplcardlal activation occurred In the anterior right ventricle In all patients. In 9 patients, it was the only eplcardlal breakthrough point. One patient had a single Inferior left ventricular breakthrough point. Eplcardlal activation spread from the right ventricle towards the left ventricle in both the anterior and inferior direction. Latest eplcardlal activation occurred at the base of the left ventricle In 9 patients and the base of the right ventricle In 1.When compared with patients with coronary artery disease, normal ventricular contraction, and no left ventricular hypertrophy, patients with hypertrophy had fewer left ventricular breakthrough points (p <0.001) and were more likely to have latest activation at the left ventricular base (p <0.001).We conclude that left ventricular hypertrophy Is associated with marked changes In the pattern of epicardlal activation. These changes may reflect delay In spread from endocardium due to the increased wall thickness.     

Transcutaneous stimulation of the heart ventricles: its effectiveness, comfort during the examination and new diagnostic possibility

An attempt of assessment of transcutaneous cardiac pacing tolerance in healthy volunteers was carried out as well as abilities of this method utilization for examination of retrograde atrioventricular conduction. Ventricles were paced through highohm electrodes positioned on the chest wall with simultaneous recordings of transoesophageal ecg at the level of the left atrium and the sphygmogram of the right common corotid artery. Pacing perception threshold, skeletal muscle stimulation threshold, cardiac pacing threshold, algesic and myo-respiratory threshold of examination tolerance were estimated. Effective ventricular pacing within the range of stimulation tolerance was obtained in 10 of 15 patients (67%). Mean ventricular pacing threshold was higher than pacing perception and skeletal muscles stimulation thresholds (42 mA; 9.4 mA and 20.2 mA). Ventricular pacing threshold was lower than algesic and muscles thresholds of examination tolerance (60-70 mA) warranting relatively good tolerance of transcutaneous cardiac ventricular pacing. In 8 of 10 persons with effective ventricular stimulation retrograde a-v nodal conduction was stated which proved that transcutaneous cardiac ventricular stimulation can be used for noninvasive assessment of retrograde a-v nodal conduction.     

Epicardial and endocardial activation in patients with endocardial cushion defect

Epicardial and left ventricular endocardial activation were assessed in 5 patients (aged 4 months to 9.5 years) with endocardial cushion defect (ECD) during surgical repair. Epicardial activation was recorded from 40 to 47 sites over the epicardium; left ventricular endocardial activation was measured at 3 sites immediately after institution of cardiopulmonary bypass. Compared with the reported activation sequence in normal hearts, the pattern of excitation in hearts of patients with ECD was abnormal; epicardial excitation began at the left ventricular diaphragmatic surface and spread laterally and anteriorly over the anterobasal left ventricle. It then merged with right ventricular wavefronts ending along the right ventricular anterior atrioventricular groove and outflow tract. Left ventricular endocardial activation also occurred earliest in the diaphragmatic segment of the left ventricle with later wavefronts recorded laterally and anteriorly. This study demonstrates, for the first time in human subjects, correlation between left ventricular epicardial and endocardial activation in patients with ECD. The data indicate that earliest endocardial and epicardial activation occurs at the left ventricular diaphragmatic segments of the heart, and are consistent with the known posterior and inferior displacement of the specialized atrioventricular conduction system in patients with ECD.     

Changes in canine ventricular fibrillation threshold induced by verapamil, flecainide and bretylium

The changes produced by verapamil, bretylium and flecainidein both ventricular fibrillation threshold (VFT) and ventricularrepetitive response threshold (VRRT) were studied in 20 closed-chestdogs anaesthetized with pentobarbital. Right ventricle endocardium thresholds were determined usingbipolar electrode catheters. Increasing intensity stimulus trains(200ms, 4ms, 100 Hz, 1mA steps) were delivered 50 ms after QRS;VRRT and VFT were calculated before and after drug administration.Three study groups were considered according to the drug assayed:(1) verapamil 0.15 mg . kg^–1 n=6; (2) flecainide 2.0 mg.kg^–1 n=7, and (3) bretylium 10.0mg .kg^–1 n=7. Flecainidesignificantly increased VRRT (4.8±1.4 vs 9.4±1.5mA, P<0.05), but the latter failed to change in the othertwo groups. VFT remained unchanged with verapamil, increasedslightly post-flecainide (10.3±4.6 vs 12.4±4.1,P<0.05 mA) and markedly post-bretylium (10.3±4.;6vs 17.3 ± 7.5, P<0.05). VFT changes were significantlycorrelated (r=0.77, P<0.05) with the effective refractoryperiod changes in the bretylium group. Thus, of the three drugs tested, bretylium induced the greatestVFT increases without modifying VRRT, whereas flecainide affectedboth parameters. Only in the bretylium series were ERP changessignificantly correlated to the corresponding VFT changes. Thissuggests that ventricular fibrillation threshold increase isnot a non-specific property of antiarrhythmic drugs. Changesin ventricular repetitive response threshold may provide additionalinformation