Tachycardia In Humans Research Articles

Cerebral blood flow velocity during induced ventricular fibrillation and ventricular tachycardia in humans

Cerebral blood flow velocity during induced ventricular fibrillation and ventricular tachycardia in humans

Three-dimensional mapping of the initiation of nonsustained ventricular tachycardia in the human heart.

Elucidation of the electrophysiological mechanisms of nonsustained ventricular tachycardia (VT) in humans is required to define the relationship between nonsustained VT and sustained VT. This goal requires, at least in part, analysis of transmural ventricular activation in patients with both sustained and nonsustained VTs. We analyzed three-dimensional intraoperative cardiac maps of extrastimuli and beats during 44 nonsustained VTs and the initiating beats of 6 sustained VTs from six patients with healed myocardial infarcts who were undergoing arrhythmia surgery. The coupling interval, total activation time, and diastolic interval of each extrastimulus and beat of nonsustained VT were compared with counterparts during sustained VT. Sites activated last during extrastimuli initiating nonsustained or sustained VTs occurred in the same region, and activation times were comparable. However, the site of earliest activation during the initial or subsequent beats of nonsustained VT was discordant from the site activated earliest during the first and subsequent beats of sustained VT in 74% of cases. The mean variance in coupling interval, but not total activation time or diastolic interval, was significantly greater for VT that terminated before the 10th cycle than for VT that sustained. When analyzed from the last extrastimulus up to the fifth VT cycle, the standard deviation of the coupling interval, but not of the total activation time, was greater for nonsustained than for sustained VTs. Electrode density was sufficient to define an arrhythmia mechanism for 36 beats of nonsustained VT. Twenty-one (58%) initiated in the subendocardium, midmyocardium, or epicardium by a macroreentrant mechanism, and 15 (42%) initiated in the subendocardium by a focal mechanism. Compared with sustained VT, nonsustained VT initiates at discordant sites, is characterized by oscillations in coupling interval but not in total activation time, and initiates by either a macroreentrant or a focal mechanism.

Role of endothelium-derived nitric oxide in coronary vasodilatation induced by pacing tachycardia in humans: K. Egashira, Y. Katsuda, M. Mohn, T. Kuga, T. Tagawa, T. Kubota, Y. Hirakawa, A. Takeshita. RIACC, Kyushu University School of Mediane, Fukuoka, Japan. Circ Res 1996;79:331–5

Endothelium-derived NO contributes to the control of coronary perfusion. We investigated the roles of NO in the metabolic coronary vasodilatation induced by rapid pacing in humans. We evaluated the dilatation of large epicardial and resistance coronary arteries during rapid atrial pacing before and after intracoronary infusion of NG-monomethyl-l-arginine (L-NMMA), an inhibitor of NO synthesis, in 19 patients without significant coronary artery disease. The diameter of the large epicardial coronary artery and coronary blood flow (CBF) were assessed by quantitative coronary arteriography and by a Doppler flow velocity measurement. An increase in the heart rate increased CBF (P<.01) and the coronary artery diameter (P<.05). L-NMMA at a total dose of 200 μmol reduced basal CBF but did not significantly affect basal coronary artery diameter, arterial pressure, or heart rate. L-NMMA inhibited the pacing-induced dilatation of the large coronary arteries (P<.05) but did not affect pacing-induced increases in CBF....

Role of endothelium-derived nitric oxide in coronary vasodilatation induced by pacing tachycardia in humans.

Endothelium-derived NO contributes to the control of coronary perfusion. We investigated the roles of NO in the metabolic coronary vasodilatation induced by rapid pacing in humans. We evaluated the dilatation of large epicardial and resistance coronary arteries during rapid atrial pacing before and after intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis, in 19 patients without significant coronary artery disease. The diameter of the large epicardial coronary artery and coronary blood flow (CBF) were assessed by quantitative coronary arteriography and by a Doppler flow velocity measurement. An increase in the heart rate increased CBF (P < .01) and the coronary artery diameter (P < .05). L-NMMA at a total dose of 200 mumol reduced basal CBF but did not significantly affect basal coronary artery diameter, arterial pressure, or heart rate. L-NMMA inhibited the pacing-induced dilatation of the large coronary arteries (P < .05) but did not affect pacing-induced increases in CBF. L-NMMA inhibited the acetylcholine-induced increase in CBF (P < .01) and acetylcholine-induced dilatation of the large epicardial coronary artery (P < .05). These results show that the contribution of NO to the metabolic vasodilatation during rapid pacing may differ between large epicardial and resistance coronary arteries in patients without significant coronary artery disease.

Role of vagal feedback from the lung in hypoxic-induced tachycardia in humans

We assessed the cardiovascular responses to systemic normocapnic hypoxia in five normal subjects, five double lung transplant patients with lung denervation and intact hearts, and five patients with denervated hearts. Progressive normocapnic hypoxia was induced over 10-15 min and maintained for 2-3 min each at 90, 87, 84, and 80% arterial O2 saturation (SaO2). Normal subjects showed the most pronounced mean increase in heart rate (dHR/dSaO2 = 0.86 +/- 0.13 beat/min per 1% SaO2). Three lung-denervated subjects had normal tachycardiac responses (1.6, 0.9, and 0.69 beats/min per 1%), whereas the other two had distinctly lower responses (0.34 and 0.39 beat/min per 1%). Most of the lung-denervated subjects also showed a significant tachycardia with even mild hypoxia; none showed a bradycardiac response to any level of hypoxia. In the heart-denervated group, hypoxic tachycardia was significantly lower than normal (0.29 +/- 0.13 beat/min per 1%). We conclude that vagal feedback from the lungs is not required for the normal chronotropic response to hypoxia in humans; however, this mechanism may contribute significantly to the marked variability in hypoxic-induced tachycardia found among human subjects. These data in humans contrast with the progressive bradycardiac response to hypoxia reported in vagally denervated (or nonhyperpneic) dogs and cats.

1 Sevoflurane: an update

Summary A major question often asked about sevoflurane is why, if it meets all the needs of the practitioner, was it not introduced earlier? After all, the drug has been around since 1975. Most of the reasons sevoflurane has been somewhat of a ‘late bloomer’ have been due to hesitations on the part of the drug manufacturers. This has been discussed in a recent editorial ( Brown and Frink, 1992 ). The authors feel that sevoflurane is a useful drug which may have certain advantages over currently available halogenated anaesthetics. Some of the advantages of sevoflurane are listed. 1. Cardiovascular. There is reason to believe that in clinical practice sevoflurane may cause less cardiovascular depression than other drugs. These clinical impressions are subtle, but seem inevitable after clinical familiarity with the drug is obtained. It does not appear to produce tachycardia in humans. Certainly, sevoflurane is less arrhythmogenic than other inhalation anaesthetics in use. The anaesthetic is very ‘user friendly’. 2. Induction and awakening time are remarkably short and smooth. 3. Paediatric inhalation induction is unparalleled with other anaesthetics, including halothane. Certainly sevoflurane may be a ‘niche’ drug for such use, to answer a question poised in the introduction of this chapter. 4. The potential toxicity for interaction of sevoflurane and CO 2 absorbents is probably more theoretical than real. This is an area, however, where more investigation, both clinical and laboratory, is needed. In summary, sevoflurane at the present time seems to offer many advantages over currently available drugs. Its place in practice will be determined by experience in clinical practice.

Clinical and in vivo antiarrhythmic potential of sodium-hydrogen exchange inhibitors

Intracellular acidification may be the initial stimulus for a cascade of events contributing to intracellular calcium overload. Ischaemia results in the accumulation of lactate and other proton donors causing intracellular acidification. During reperfusion the activity of the Na+/H+ exchanger recovers, allowing extrusion of protons at the expense of increases in intracellular sodium. The rise in intracellular sodium decreases the gradient required for sodium calcium exchange, resulting in accumulation of intracellular calcium. These data are in keeping with the pathophysiological model that the Na+/H+ exchanger is an important part of a cascade leading from intracellular acidosis to intracellular sodium loading followed by calcium overload. From this model we predicted that amiloride would be antiarrhythmic. In 1988, we reported that low concentration of amiloride (0.1-0.3 microM) suppresses the induction of sustained ventricular tachyarrhythmias in dogs late following infarction. Amiloride suppressed inducible ventricular tachycardia in approximately 50% of the animals. In an extension of this work we assessed the efficacy of amiloride in suppressing inducible ventricular tachycardia in humans who presented with symptomatic ventricular tachycardia. In that study, amiloride manifested antiarrhythmic activity, but not to the degree that was observed in our dog model. Six of 31 patients (19%) had complete suppression of induced ventricular tachycardia. In an extension of this work, we assessed in our in vivo dog model which of the pharmacological effects of amiloride were associated with antiarrhythmic efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Clonidine and Lidocaine Inhibition of Isoflurane-induced Tachycardia in Humans

Clonidine and Lidocaine Inhibition of Isoflurane-induced Tachycardia in Humans

Cardiovascular and respiratory effects of adenosine in humans after pulmonary denervation.

Adenosine infusion causes tachycardia in normal subjects. A proposed mechanism is secondary pulmonary stretch receptor activation due to hyperventilation, induced by direct stimulation of carotid body chemoreceptors by adenosine. We examined responses to adenosine (incremental doses given by intravenous infusion, 5 min each rate) in six normal volunteers and six lung-transplant recipients with pulmonary denervation. Adenosine caused chemoreceptor stimulation in both groups with minute ventilation increasing from 5.8 +/- 0.4 to 10.7 +/- 1.3 l/min (P < 0.05) in the volunteers and from 4.8 +/- 0.4 to 9.2 +/- 0.8 l/min (P < 0.001) in the lung-transplant recipients. There was no difference in the magnitude of the ventilatory increase between the two groups (P = NS at all infusion rates). Adenosine produced tachycardia in both groups, with heart rate increasing from 66 +/- 5 to 84 +/- 3 beats/min (P < 0.01) in the volunteers and from 82 +/- 6 to 110 +/- 6 beats/min (P < 0.05) in the lung-transplant recipients. There was no difference in the magnitude of the heart rate response between the two groups (P = NS at all infusion rates). These data suggest, contrary to previous thinking, that pulmonary stretch receptor activation does not contribute to adenosine-induced tachycardia in humans.

Experimentally created atrioventricular node reentrant tachycardia in the dog: Evidence of a brake system for nodal reentry in the anterior interatrial septum

Objectives. The purpose of the study was to investigate the hypothesis that nodal approaches of both anterior and posterior atrial input sites of the atrioventricular (AV) node contribute to part of the circuit of AV node reentrant tachycardia. Thus, tachycardia might be elicited by a premature atrial impulse that arrived at the AV node through one input site while blocked at another.Background. Atrioventricular node reentrant tachycardia is the most common supraventricular tachycardia in humans, yet the exact pathway of the reentrant circuit is unknown. Methods. In eight dogs, an operation that blocked atrial impulses from the anterior input site to the AV node was performed through a right thoracotomy with the inflow occlusion method. The right atrial free wall and the anterior atrial septum between the sinoatrial node and the AV node were completely divided, whereas the tissues within the triangle of Koch remained intact. Thus, atrial impulses were blocked from the anterior input site in the right atrium and the atrial septum and were conducted only through the left atrial free wall to the posterior atrial septum into the AV node.Results. In a baseline electrophysiologic study before operation, dual AV conduction pathways were demonstrated in seven of eight dogs, but none of the seven had inducible AV node reentrant tachycardia. A repeat study 1 week postoperatively revealed that 1) both PR and AH intervals were prolonged during sinus rhythm (p < 0.01); 2) anterograde and retrograde conduction of the AV node showed no significant changes; and 3) AV node reentrant tachycardia was induced in four dogs (50%), of which three had sustained tachycardia.Conclusions. These results are compatible with the hypothesis that both nodal approaches of atrial input sites of the AV node contribute to part of the circuit of AV node reentrant tachycardia. They also confirm Moe's hypothesis of the existence of a brake system that prevents sustained AV node reentry. Our data suggest that the brake system is located in the anterior atrial septum.

Electrocardiographic correlates of spontaneous termination of ventricular tachycardia in patients with coronary artery disease.

In vitro studies have reported that beat-to-beat variance in tachycardia cycle length and in conduction and repolarization properties can result in spontaneous termination of reentrant arrhythmias. The purpose of this study was to define the ECG patterns associated with spontaneous termination of ventricular tachycardia in humans late after myocardial infarction. The QRS durations, QT intervals, and cycle lengths were measured on a beat-to-beat basis during episodes of sustained and spontaneously terminating ventricular tachycardias (VT) induced at antiarrhythmic drug-free and drug-assessment electrophysiological studies. Twenty-six patients were studied. Four categories of inducible ventricular tachycardia were studied: inducible sustained ventricular tachycardia in an antiarrhythmic drug-free state, spontaneously terminating ventricular tachycardia in an antiarrhythmic drug-free state, sustained ventricular tachycardia on antiarrhythmic therapy, and spontaneously terminating ventricular tachycardia on antiarrhythmic therapy. The ECG patterns that were statistically related to spontaneous termination of ventricular tachycardia included impingement of the QTP interval on the tachycardia cycle length (P < .001) both in the presence and absence of drugs, transient shortening of QRS just before termination, and paradoxical prolongation of QTP after abrupt shortening of ventricular tachycardia cycle length. In addition, greater beat-to-beat variances in tachycardia cycle lengths, QT intervals, and QRS durations were statistically associated with spontaneously terminating ventricular tachycardia. These ECG patterns did not occur during sustained episodes of ventricular tachycardia during the antiarrhythmic drug-free state or during ineffective antiarrhythmic drug therapy. A dynamic interplay between QRS duration, QT interval, and cycle length of tachycardia and their variances are associated with spontaneous termination of ventricular tachycardia in humans late after infarction. This study of ECG changes associated with spontaneous termination of ventricular tachycardia provides insight into potential mechanisms of antiarrhythmic drug efficacy.

Characterization of double potentials during ventricular tachycardia. Studies during transient entrainment.

Double potentials have been recorded during reentrant tachycardias in animal models. Although they have also been recorded during ventricular tachycardia in humans, their meaning is uncertain. We used transient entrainment as a method to help further understand the meaning of double potentials recorded during ventricular tachycardia in humans. Three patients with ventricular tachycardia (cycle lengths, 500, 450, and 290 msec) were studied. During transient entrainment of ventricular tachycardia (pacing cycle length, 470-260 msec), both double potential deflections were captured at the pacing cycle length. One deflection was captured with a short activation time, and the other deflection was captured with a long activation time. During ventricular pacing, the deflections were associated by the long rather than the short interdeflection interval. At termination of pacing, each double potential deflection was associated with separate but sequential QRS complexes, and each deflection maintained the same electrogram morphology at relatively "slow" overdrive pacing rates. The short interdeflection interval shortened further with faster pacing rates (to less than the ventricular refractory period), making it unlikely that both deflections of the double potential represent active depolarization of the same tissue. In two patients, at a critically rapid pacing rate, one of the double potential deflections changed morphology abruptly, associated with a shortened stimulus-to-double potential time interval (from 520 to 110 msec and from 530 to 240 msec, respectively), indicating a change in the direction of activation that caused that deflection. Interruption of ventricular tachycardia was associated with disappearance of the double potentials at the same recording site. The double potentials did not immediately bracket an area of slow conduction. These data suggest that double potentials recorded only during ventricular tachycardia represent activation wave fronts on either side of an area of block within a reentrant circuit. Thus, double potentials recorded during ventricular tachycardia in these patients do not appear to represent slow conduction per se but rather appear to represent an area of block at the center of a reentrant circuit around which the reentrant wave front circulates.

Reentrant and focal mechanisms underlying ventricular tachycardia in the human heart.

To determine the mechanisms of ventricular tachycardia (VT) in humans, three-dimensional intraoperative mapping of up to 156 intramural sites was performed in 13 patients with healed myocardial infarction and refractory VT. Mapping was of sufficient density to define the mechanism of 10 VTs in eight patients. In five of 10 cases, sustained VT was initiated in the subendocardium or epicardium by intramural reentry with marked conduction delay as well as functional and anatomic block most prominent in the subendocardium and midmyocardium. The initiating beats of reentrant VT induced by programmed electrical stimulation arose in the endocardium or midmyocardium by progressive slowing of conduction leading to unidirectional block. Multiple simultaneous reentrant circuits can be present. In contrast, five of the 10 sustained VTs were initiated by a focal mechanism as defined by the absence of electrical activity between the termination of one beat and the initiation of the next despite the presence of multiple intervening intramural electrode recording sites. Comparisons of the mapping data with results of histopathological analysis of tissue demonstrated that the location of infarction as well as that of adjacent fibrotic muscle determined sites of both fixed and functional conduction block during macroreentrant VT and that slowing of conduction occurred in a direction transverse rather than longitudinal to fiber orientation. Both intramural reentry and a focal mechanism underlie sustained VT in patients with healed myocardial infarction.

Ventricular Arrhythmias in Ischemic Heart Disease

Ventricular arrhythmias remain the leading cause of death from coronary artery disease. This review summarizes current thinking in several areas relating to the pathophysiology, prognosis, and therapy of ventricular arrhythmias associated with acute and chronic coronary artery disease syndromes. The experimental basis of arrhythmias in the setting of acute myocardial ischemia and chronic myocardial infarction is described, stressing the important pathophysiologic differences between these two conditions. The effects of the autonomic nervous system as a key modulator of ischemic arrhythmogenesis are discussed. Insights, derived from endocardial mapping studies, into the nature of ventricular tachycardia in humans with chronic myocardial infarction are described, including implications for risk stratification and therapy to prevent arrhythmia recurrence. Current therapeutic principles are discussed in the management of ventricular arrhythmias associated with coronary artery disease, including pharmacologic approaches, surgical and catheter ablation, and automatic implantable cardioverting and defibrillating devices.

Mechanisms of supraventricular tachycardia

Programmed electrical stimulation of the heart in combination with intracardiac recordings has contributed a wealth of new information on the mechanisms and pathways of supraventricular tachycardia in humans. This knowledge has resulted in better treatment approaches to these patients. Questions still remain, however, about the mechanisms of atrial flutter and fibrillation and of some types of atrial tachycardia. The location of the circuit in paroxysmal atrioventricular nodal tachycardia also continues to puzzle investigators. The use of refined mapping techniques during cardiac surgery should provide answers to these questions in the near future.

Identification and catheter ablation of a zone of slow conduction in the reentrant circuit of ventricular tachycardia in humans

Three patients who had incessant ventricular tachycardia and in whom a zone of slow conduction was identified are presented. Each patient's tachycardia was refractory to multiple antiarrhythmic drugs and was being treated with amlodarone at the time of the electrophysiologic study. The ventricular tachycardia cycle length was 500 to 580 ms. In Patients 1 and 2, a single site at the posterolateral wall or low septum in the left ventricle was identified at which overdrive pacing during ventricular tachycardia resulted in ventricular capture with a stimulus to QRS interval of 280 to 400 ms and with little or no change in the configuration of the QRS complexes during pacing as compared with during ventricular tachycardia. In Patient 3, the same phenomenon was observed at two areas in the left ventricle: at the inferior wall, overdrive pacing during ventricular tachycardia resulted in a stimulus to QRS interval of 440 to 470 ms, whereas at the posterolateral wall, the stimulus to QRS interval was 320 to 360 ms. Transcatheter shocks of 100 to 240 J delivered at the pacing sites have been successful in preventing recurrences of ventricular tachycardia over a follow-up period of 10 to 11 months.These observations may be explained by the pacing site being located within a reentrant circuit in a zone of slow conduction bounded by inexcitable tissue between the pacing site and the exit site of the reentrant circuit. In Patient 3, the variable stimulus to QRS intervals are explained by variable proximity of the pacing sites within the slow conduction zone to the exit site of the reentrant circuit. The findings of this report demonstrate that it may be possible to identify a zone of slow conduction that is a critical component of the reentrant circuit of ventricular tachycardia. Initial results suggest that this slow conduction zone may be an ideal location to deliver transcatheter shocks for the purpose of ventricular tachycardia ablation.

Atrial natriuretic factor attenuates carotid baroreflex-mediated cardioacceleration in humans.

We tested the hypothesis that infusions of atrial natriuretic factor (ANF) attenuate carotid baroreflex-mediated tachycardia in humans. The afferent profile from carotid baroreceptors was altered by repeated, intermittent random applications of neck suction (40 mmHg) and neck pressure (20 mmHg) to healthy volunteers during supine control and during infusions of 15 (n = 6) or 25 ng.kg-1.min-1 (n = 9) of alpha-human ANF or during placebo (n = 9). ANF infusions resulted in five- and eightfold increases of plasma ANF, which did not alter base-line cardiac interval, blood pressure, respiratory sinus arrhythmia, plasma renin activity, vasopressin, or norepinephrine but did reduce central venous pressure. Reflex bradycardic responses were unaltered during these infusions. Reflex tachycardic responses to carotid compression were significantly blunted (up to 40%) during infusions of ANF and were unchanged during placebo. These responses may be due to a sensitization of cardiac receptors and augmentation of cardiac-vagal afferent traffic by ANF, which diminishes reflex cardiac-sympathetic outflow during carotid baroreceptor unloading.

Mexiletine and Quinidine in Combination in an Ischemic Model: Supra-Additive Antiarrhythmic and Electrophysiologic Actions

Combination therapy with mexiletine and quinidine has been shown to be more effective than either agent alone in the treatment of ventricular tachycardia in humans. To assess the electrophysiologic correlates of this enhanced antiarrhythmic effect, concentration-response relationships of mexiletine and quinidine alone and in combination were evaluated in 117 isolated perfused rabbit hearts after circumflex occlusion-reperfusion. Normal and infarct zone recordings included monophasic action potential duration, ventricular effective refractory period, and conduction time during constant rate pacing. Ventricular fibrillation occurred in all 18 "vehicle only"-treated hearts during programmed electrical stimulation (S2). High-concentration mexiletine therapy was more effective in protecting against malignant ventricular arrhythmias than was quinidine. Both therapies produced concentration-dependent prolongation of ischemic zone conduction and refractoriness. When low concentrations of mexiletine and quinidine were combined (concentrations which when given alone had little or no electrophysiologic or antiarrhythmic activity) antiarrhythmic activity was seen which was greater than that seen with high-concentration single treatment. Low-concentration combination therapy was also associated with significantly greater prolongation of infarct zone conduction time and refractoriness. In conclusion, low-concentration combination treatment with mexiletine and quinidine prolonged infarct zone conduction time and refractoriness to a greater extent than was seen with single therapy at matched concentrations. These electrophysiologic effects were associated with enhanced antiarrhythmic activity.

The mechanisms of ventricular tachycardia in humans determined by intraoperative recording of the electrical activation sequence

We recorded ventricular activation sequence during ventricular tachycardia in 76 patients who underwent surgical therapy of refractory ventricular tachycardia. Ventricular tachycardia arose from a discrete site (focal origination) in 28 patients (37%) or resulted from reentry around scar (macroreentry) in 22 patients (29%). The mechanism responsible for ventricular tachycardia was not discernable in the remaining 26 patients (34%), usually because of inadequacy of activation data. We conclude: (1) although focal originating of ventricular tachycardia is common, more frequently the mechanism is either macroreentry or uncertain, as assessed by conventional recording techniques; thus, a search for the “site of earliest activation” during ventricular tachycardia frequently may fail to direct rationally the operative procedure; (2) conventional techniques for intraoperative study of electrical activation during ventricular tachycardia are inadequate.

Bradycardia-dependent triggered activity: relevance to drug-induced multiform ventricular tachycardia.

We used cesium chloride (CsCl) for electrophysiologic studies in canine hearts in vivo and in vitro to examine the mechanisms underlying ventricular arrhythmias that are related to prolonged repolarization. Cesium is known to depress normal ventricular automaticity and some experimental arrhythmias by blocking delayed outward currents and prolonging action potential duration. In 10 dogs in normal sinus rhythm, 1 to 1.5 mM/kg iv CsCl prolonged the QT (QU) interval and induced ventricular ectopy in all, including multiform ventricular tachycardia. In 12 dogs with atrioventricular block, 1 to 1.5 mM/kg iv CsCl produced marked suppression of idioventricular rates (from 45 +/- 6 to 8 +/- 4 beats/min). These low rates were then associated with bigeminy or bursts of multiform ventricular arrhythmia. Pacing at rates of 60 beats/min or more suppressed these arrhythmias. Low doses of tetrodotoxin (1 microgram/kg) also abolished these bradycardia-dependent arrhythmias without affecting the amplitude of ventricular electrograms. Tissue concentrations of cesium were determined by anatomic absorption spectroscopy in five dogs after injection of 1 mM/kg CsCl. Thirty minutes after the injection, cesium levels in Purkinje fibers were 5.3 +/- 1.0 mM/kg, levels in ventricular muscle were 4.6 +/- 0.9 mM/kg, and levels in atrial muscle were 4.1 +/- 0.8 mM/kg. In eight isolated endocardial preparations from canine ventricles, standard microelectrode techniques were used to study the effects of superfusion with 5 mM cesium. After 30 min, we observed early afterdepolarizations interrupting phase 3 of Purkinje fiber action potentials that already showed prolonged repolarization. Slowing the rate generated single or multiple action potentials arising from partially repolarized levels of membrane potentials (-80 to -65 mV). Pacing rates of 30 to 60 beats/min diminished the afterdepolarizations and suppressed the spontaneous beats. Tetrodotoxin at a concentration of 10(-8) g/ml, which did not affect upstroke velocity, abolished the afterpotentials. We conclude that cesium induced bradycardia-dependent ventricular arrhythmias caused by early afterdepolarizations. These data suggest that an inward current, probably carried by sodium ions, appears to be essential for the occurrence of this phenomenon. The association of delayed repolarization, afterdepolarizations, and triggered activity has similarities to the phenomenon of drug-induced prolongation of the QTU interval associated with multiform ventricular tachycardia in humans, i.e. "torsades de pointes."