Inappropriate discharges by fourth generation implantable cardioverter defibrillators in patients with ventricular arrhythmias.

The study prospectively investigated the incidence, cause and efficient management of inappropriate discharge by the fourth generation implantable cardioverter-defibrillator (ICD) system in 45 patients (mean age, 57+/-16 years). During the follow-up period of 27+/-17 months, 18 patients (40%) experienced one or more inappropriate therapies: sinus and supraventricular tachycardia (15 patients) and T wave oversensing (3 patients). In the 15 patients, re-programming of the tachycardia detection interval and/or additional treatment with beta-blocking agents were effective. In the 3 patients with T wave oversensing, the arrythmia was associated with an increase in T wave amplitude, change in T wave morphology and decreased R wave amplitude, and re-programming of the sensitivity of the local electrogram or changing the number of intervals to detect ventricular tachycardia decreased the number of inappropriate discharges in all 3 patients. In conclusion, inappropriate therapies are common problems in patients treated with the fourth generation ICD system, but most of them can be resolved using the dual-chamber ICD system. However, in patients with T-wave oversensing, it is difficult to avoid inappropriate discharge completely, even if the dual-chamber ICD system is implanted.

Correlation between the effective refractory period and activation-recovery interval calculated from the intracardiac unipolar electrogram of humans with and without dl-sotalol treatment.

In experimental studies and/or human body surface mapping, the activation-recovery interval (ARI) is used as a parameter to estimate local repolarization. However, it has not been clarified whether the ARI calculated from the intracardiac unipolar electrogram of humans reasonably represents the local effective refractory period (ERP). Measurement of ARIs at multiple ventricular sites can be helpful in assessing the dispersion of ventricular refractoriness of humans, so we examined the relationship between ERP and ARI in the control state and under treatment with dl-sotalol during clinical electrophysiologic studies (EPS). Of 19 patients, an EPS was performed in the control state in 12 and during treatment with dl-sotalol in the other 7. Quadripolar electrode catheters with an interelectrode distance of 5 mm were placed at the right atrium and in the right ventricle. Using atrial pacing, the heart rate was increased incrementally by 10 beats/min, and ERP and ARI were measured for each pacing rate. The ERP at the right ventricle was measured by single extrastimulation between the first and third distal electrodes of the catheter in the right ventricle, and the ARI was calculated from the second distal unipolar electrode of the same catheter as the interval between the minimum derivative of the intrinsic deflection and the maximum derivative of the T wave. In all patients, the unipolar electrogram was stable during the entire EPS, and 83 data points in the control group and 50 in the dl-sotalol group were analyzed. At each pacing rate, the beat-to-beat difference of ARI was less than 10 ms. As the atrial pacing rate increased, the ERP and ARI were progressively shortened, and linear regression analysis revealed an excellent correlation between ERP and ARI. At the same pacing rate, the ERP and ARI in the dl-sotalol group were longer than those in the control group, but no difference was observed in the slope (close to 1.0) and in the intercept of the regression lines between ERP and ARI. In the human ventricle, the ARI calculated from the intracardiac unipolar electrogram represents the local ERP both in the control state and under treatment with dl-sotalol. The ARI can be used as a parameter of local refractoriness and used to study the distribution of refractoriness in the human ventricle.

Discrepancy between inducibility of ventricular tachycardia and activity of cardiac sarcoidosis. Requirement of defibrillator implantation for the inactive stage of cardiac sarcoidosis.

Monomorphic ventricular tachycardia (VT) developed in two patients with cardiac sarcoidosis. Before treatment with prednisolone, technetium or gallium scintigram revealed abnormal accumulation in the heart and bilateral hilar lymph nodes, but programmed electrical stimulation failed to induce VT in either case. Prednisolone was administered and the abnormal accumulation of the scintigra ms disappeared. However, VT became reproducibly inducible, and in one of the patients, transient entrainment was demonstrated in clinical VT morphology. Defibrillators were implanted in both patients. Some VTs associated with cardiac sarcoidosis are due to reentry, and inducibility of VT is not associated with the activity of cardiac sarcoidosis. Even though steroid therapy suppresses the activity of cardiac sarcoidosis, defibrillator implantation is necessary to prevent a possible arrhythmic event during the follow-up.

Periodic lateralized epileptiform discharges in influenza B-associated encephalopathy.

An 18-year-old woman presented with coma, hemicomvulsions, and transient periodic lateralized epileptiform discharges (PLEDs). Serological tests were positive for influenza B, and cerebrospinal fluid PCR for herpes simplex virus DNA was negative. Magnetic resonance imaging later showed abnormal signal intensity in the temporal lobe ipsilateral to the PLEDs. Influenza-associated encephalopathy may cause hemiconvulsions and PLEDs, and can mimic herpes simplex encephalitis.

Role of alpha1-blockade in congenital long QT syndrome: investigation by exercise stress test.

Beta-blockade is widely reported to reduce the incidence of syncope in 75-80% of patients with congenital long QT syndrome (LQTS). However, despite full-dose beta-blockade, 20-25% of patients continue to have syncopal episodes and remain at high risk for sudden cardiac death. In some patients refractory to beta-blockade, the recurrence of arrhythmias is successfully prevented by left stellate ganglionectomy, and also by labetalol, a nonselective beta-blockade with alpha1-blocking action. These observations suggest that not only beta-adrenoceptors, but also alpha1-adrenoceptors, play an important pathogenic role, especially under sympathetic stimulation, in LQTS. The clinical effects of alpha1-blockade in congenital LQTS were investigated in 8 patients with familial or sporadic LQTS. Two measurements of the QT interval were taken, from the QRS onset to the T wave offset (QT) and from the QRS onset to the peak of the T wave (QTp). Using the Bruce protocol, an exercise test was performed after administration of beta-blockade alone and again after administration of alpha1-blockade. The following were compared: (1) Bazzet-corrected QT (QTc) and QTp (QTpc) intervals in the supine and standing position before exercise and in the early recovery phase after exercise; and (2) the slopes (reflecting the dynamic change in the QT interval during exercise) of the QT interval to heart rate were obtained from the linear regression during the exercise test. In the supine position before exercise, there was no change in the QTc before or after the addition of alpha1-blockade (498+/-23 vs 486+/-23 ms [NS]). However, in the upright position before exercise and in the early recovery phase after exercise, QTc was significantly shortened from 523+/-21 to 483+/-22ms (p<0.01), and from 521+/-30 to 490+/-39ms (p<0.01), respectively, by alpha1-blockade. The QTpc was unchanged in any situation. Consequently, QTc-QTpc was significantly shortened by alpha1-blockade in the upright position before exercise and in the early recovery phase after exercise (131+/-36 to 105+/-37ms (p<0.05), and 132+/-29 to 102+/-31 ms (p<0.01), respectively). The slopes of the QT interval-heart rate relation by linear regression became significantly steeper from -2.23+/-0.38 to -2.93+/-0.76 (p<0.01) with the addition of alpha1-blockade. The findings suggest that the addition of alpha1-blockade attenuated the exercise-induced prolongation of the QT interval and that the rate adaptation of the QT interval to heart rate during exercise was improved. This indicates that additional treatment with alpha1-blockade may be beneficial to prevent cardiac events in LQTS patients in whom ventricular arrhythmia is resistant to beta-blockade.

Effect of atropine on QT prolongation and torsade de pointes induced by intracoronary acetylcholine in the long QT syndrome.

We recently reported a marked QT prolongation and torsade de pointes (TDP) induced by an intracoronary acetylcholine (ACh) administration in patients with long QT syndrome, but the mechanism was not determined. In the present study, the effect of atropine on the ACh-induced QT prolongation and TDP was studied in long QT syndrome. Nine patients with congenital long QT syndrome were studied. ACh at doses of 20, 50, and 100 microg were injected in a stepwise manner into the left main coronary artery, and the changes in the QT interval were measured. In 4 of the 9 patients, ACh administration at a dose of 100 microg was repeated after an intravenous atropine administration at a dose of 0.5 mg. The QT intervals were measured using 12-lead electrocardiograms, and the data were compared before and after atropine administration. The coronary angiograms were normal and coronary spasm was not induced by ACh in all patients. The intracoronary administration of ACh at a dose of 100 microg significantly prolonged the corrected QT interval (QTc), from 511 +/- 26 to 629 +/- 40 ms (p <0.05). In 5 of the 9 patients, TDP was induced and was spontaneously terminated within 10 seconds (n = 4) or required direct-current shock (n = 1). After atropine administration, intracoronary ACh at the same dose resulted in no QT prolongation, and the QTc interval remained unchanged (525 +/- 29 vs 520 +/- 21 ms before and after atropine), and no TDP was induced. These findings indicate that the muscarinic receptor is involved in ACh-induced QT prolongation and TDP, both of which were prevented by the atropine administration.

Both low and high energy cardioversion induced accelerated ventricular tachycardia in a patient treated with an implantable cardioverter defibrillator.

A 72-year old male with an old myocardial infarction who had drug-refractory ventricular tachyarrhythmias received an implantable cardioverter-defibrillator (ICD). The patient did not take his prescribed beta-blocking agent for two days, following which he experienced six discrete shocks for spontaneous VT while riding his bicycle. Both 5J and 30J cardioversions were ineffective at terminating the VT and accelerated VT developed following the shocks. After admission, an electrophysiological study was performed while he was taking the beta-blocking agent, both low and high energy cardioversions reproducibly terminated the clinical VT without showing any accelerated rhythm. These findings suggest that the increase in sympathetic discharge may enhance the proarrhythmic potential of ICDs.

Comparison of electrophysiologic effects of intravenous E-4031 and MS-551, novel class III antiarrhythmic agents, in patients with ventricular tachyarrhythmias.

Electrophysiologic effects of intravenous E-4031 and MS-551, novel class III antiarrhythmic agents, were evaluated in 5 and 6 patient with ventricular tachyarrhythmia, respectively. Six patients had sustained ventricular tachycardia (VT) and 5 had ventricular fibrillation (VF). Electrophysiologic study was performed before and after administration of E-4031 and MS-551 [E-4031; loading infusion 9 micrograms/kg for 5 min + 0.15 microgram/kg/min, MS-551; loading infusion 0.3 mg/kg for 5 min + 0.01 mg/kg/min]. The QT intervals were significantly prolonged after administration of E-4031 and MS-551 from 409 +/- 37 to 455 +/- 49 msec (11%), and from 359 +/- 52 to 411 +/- 63 msec (14%), respectively. The QTc intervals were significantly prolonged from 457 +/- 17 to 494 +/- 24 msec (8%), and from 410 +/- 36 to 452 +/- 47 (10%), respectively. There were no significant differences in the QT and QTc intervals between these two agents. The right ventricular effective refractory period (VERP) with E-4031 was prolonged at 600 (from 244 +/- 27 to 270 +/- 31 msec, 11 +/- 2%), 400 (from 222 +/- 23 to 242 +/- 24 msec, 9 +/- 3%), and 300 msec (from 206 +/- 19 to 218 +/- 25 msec, 6 +/- 4%), and those with MS-551 were prolonged at 600 (from 240 +/- 23 to 268 +/- 23 msec, 12 +/- 2%), 400 (from 225 +/- 22 to 250 +/- 24 msec, 11 +/- 4%), and 300 msec (from 213 +/- 14 to 228 +/- 18 msec, 7 +/- 4%). Both E-4031 and MS-551 prolonged VERP in a "reverse" use-dependent manner without changing the conduction velocity. E-4031 prevented the induction of VT in one patient. MS-551 prevented the induction of VT and VF in one patient each. Further evaluation of these selective class III agents may be needed to determine if higher doses are required to achieve the pharmacological effects in patients with ventricular tachyarrhythmias.

Comparison of arrhythmogenicity of atrial pacing at several right atrial pacing sites: evaluation of canine atrial electrograms during atrial pacing and arrhythmogenicity for atrial fibrillation.

The changes in the duration of atrial electrograms and the appearance of AF during atrial pacing were compared among five atrial pacing sites in dogs to clarify the arrhythmogenicity of atrial pacing at different atrial pacing sites. In seven mongrel dogs (15-20 kg), the right atrial surface was exposed by right thoracotomy. Atrial electrograms were recorded via bipolar electrodes with an interelectrode distance of 1.2 mm at four right atrial sites: (1) the high right atrium (HRA), (2) the mid-right atrium (MRA), (3) the low right atrium (LRA), and (4) the center of the pectinate muscle (PM). The duration of the atrial electrograms at these four recording sites were measured during atrial pacing with fixed cycle lengths of 200, 150, and 120 ms delivered at five atrial sites: (1) the HRA, (2) the inferior vena cava (IVC), (3) the right atrial appendage (RAA), (4) Bachman's bundle (BB), and (5) the atrial septum (AS). In each dog, the atrial pacing with the 120-ms cycle length was performed five times at each pacing site to evaluate the inducibility of AF. When AF was induced, the atrial recording site which first showed a fragmented atrial electrogram was considered the initiation site of the AF. AF was induced during 9 of 35 episodes of atrial pacing at the HRA site, 11 of 35 at the IVC site, 5 of 35 at the RAA site, 3 of 35 at the BB site, and none at the AS site. The initiation site of AF was in the HRA site in 11 of 28 episodes of induced AF, in the MRA site in 9 of 28, and in the LRA site in 8 of 28. At each recording site, the shorter the paced cycle length, the longer the duration of the atrial electrogram regardless of the pacing site. During the atrial pacing with the 200-ms cycle length, the HRA pacing resulted in the shortest duration of the atrial electrogram at each recording site in comparison with the other pacing sites. However, during atrial pacing at the two shorter paced cycle lengths, the duration of the atrial electrogram was shorter during the pacing at the BB or AS sites in comparison with the other three pacing sites, i.e., the HRA, IVC, and RAA sites. These results were the same for all atrial recording sites, but the prolongation of the atrial electrogram was most prominent at the HRA and MRA recording sites, which are most likely initiation sites of the induced AF. In the canine atria, (1) the initiation sites of AF were likely to be the HRA, MRA, or LRA sites in comparison with the PM site; and (2) the atrial pacing at the BB or AS sites was considered less arrhythmogenic for AF than the pacing at the HRA, LRA, or RAA sites.

The use of the block cycle length as a safe and efficient means of interrupting sustained ventricular tachycardia and its pharmacological modification.

In nine patients who had inducible monomorphic sustained ventricular tachycardia (VT), rapid pacing was performed in 11 episodes of morphologically distinct VT at progressively shorter cycle lengths and VT was interrupted at a critical cycle length. The VT interrupting critical cycle length was defined as the block cycle length (BCL) and the effect of Class I antiarrhythmic drugs were examined. Both the VT cycle length (VTCL) and the BCL were prolonged after administration of either drug. The overall mean ratio of the BCL to the VTCL was unchanged after procainamide administration, but increased after the use of mexiletine. The ratio, however, varied in individual VTs and the BCL after treatment with Class I antiarrhythmic drugs could not be predicted from the ratio baseline value, although the ratio was always > 60% and the hazard of VT acceleration might be avoided if the BCL is used.

Use-dependent electrophysiologic effects of DL-sotalol and modulation by isoproterenol in the human ventricle.

The interaction between dl-sotalol and isoproterenol on the ventricular effective refractory period (VERP) and conduction were examined in an electrophysiologic study of 9 patients at drug-free baseline, after 14 days of dl-sotalol administration (320 mg/day), and after the administration of isoproterenol. In all 9 patients, ventricular tachyarrhythmia could not be induced after dl-sotalol treatment. Isoproterenol was administered as a loading dosage of 0.025 microgram/kg for 5 min with a maintenance dosage of 0.0025 microgram/kg/min. The VERP and the QRS duration were determined at paced cycle lengths of 600, 400 and 300 msec. DL-sotalol and dl-sotalol + isoproterenol had no effect on ventricular conduction at the three cycle lengths. The VERP was significantly prolonged after dl-sotalol treatment at paced cycle lengths of 600 (241 +/- 16 to 302 +/- 28 msec, p < 0.001), 400 (223 +/- 21 to 280 +/- 23 msec, p < 0.001) and 300 msec (202 +/- 16 to 256 +/- 24 msec, p < 0.005), but there was a parallel shift of the VERP, suggesting the absence of use-dependent effects on the VERP. The dl-sotalol-induced VERP prolongation was partially reversed by isoproterenol, but it remained significantly prolonged above baseline values at paced cycle lengths of 600 (241 +/- 16 to 281 +/- 18 msec, p < 0.01), 400 (223 +/- 21 to 258 +/- 20 msec, p < 0.01) and 300 msec (202 +/- 16 to 247 +/- 22 msec, p < 0.01). The shortening of the VERP was greater at longer basic cycle lengths (600 and 400 msec) than at the shorter paced cycle length (300 msec, p < .05), but the percentage increase of the VERP was similar at the three basic cycle lengths of 600 (16%), 400 (15%) and 300 (20%) msec, indicating the lack of reverse use-dependency. The absence of reverse use-dependency of dl-sotalol on the VERP, even after isoproterenol administration, may be beneficial in the therapy of ventricular tachyarrhythmias and may account in part for the high efficacy of this drug.

Intracoronary acetylcholine-induced prolongation of monophasic action potential in long QT syndrome.

Two patients with long QT syndrome, who had episodes of syncope, underwent recordings of the monophasic action potential (MAP) from the right ventricle. Intracoronary administration of acetylcholine (ACh) induced prolongation of MAP duration and caused Torsade de Pointes (Tdp) in both patients. In one patient, intravenous atropine administration did not induce any change in MAP duration. In the other patient, ACh was administered after atropine. According to the results of the present study, abnormal regulation of the muscarinic receptor-mediated K-channel may be involved in the mechanism causing prolongation of MAP duration caused by ACh administration.

Electrophysiologic effects of intravenous MS-551, a novel class III antiarrhythmic agent, on human atrium and ventricle.

The effects of intravenous MS-551, a new class III antiarrhythmic drug, on atrium and ventricle were evaluated in 6 patients with ventricular tachyarrhythmias (4 males and 2 females; mean age 45 +/- 21 years) in an electrophysiologic study. Two patients had sustained ventricular tachycardia (VT) and 4 patients had ventricular fibrillation (VF). Electrophysiologic study was performed before and after the administration of MS-551 (loading infusion 0.3 mg/kg for 5 min + 0.01 mg/kg/min). The QT and QTc intervals were significantly prolonged by MS-551 from 359 +/- 52 to 411 +/- 63 msec (p = 0.01) and from 410 +/- 36 to 452 +/- 47 (p = 0.0172), respectively. No effect was observed on the sinus cycle length, QRS duration, or AH and HV intervals in sinus rhythm. The effective refractory periods of the right atrium (AERP) were significantly prolonged at paced cycle lengths of 600 (from 222 +/- 19 to 250 +/- 23 msec, p = 0.0009), 400 (from 207 +/- 15 to 228 +/- 15, p < 0.0001) and 300 (from 193 +/- 10 to 205 +/- 8 msec, p = 0.0127) msec. Similarly, the right ventricular ERP (VERP) were significantly prolonged at paced cycle lengths of 600 (from 240 +/- 23 to 268 +/- 23 msec, p < 0.0001), 400 (from 225 +/- 22 to 250 +/- 24 msec, p = 0.0007), and 300 msec (from 213 +/- 14 to 228 +/- 18 msec, p = 0.0071). MS-551 prolonged AERP and VERP in a "reverse" use-dependent manner without changing the conduction time in patients with ventricular tachyarrhythmias. MS-551 prevented the induction of VT in 1 patient and VF in only 1 patient in this electrophysiologic study. Further evaluation of the therapeutic potential of MS-551 using higher dosages is necessary.

The usefulness of Holter monitoring in selecting pharmacologic therapy for patients with sustained monomorphic ventricular tachycardia: studies in patients in whom no effective pharmacologic therapy could be determined by electrophysiologic study.

The usefulness of Holter monitoring (HM) in selecting pharmacologic therapy for patients with sustained monomorphic ventricular tachycardia (VT) was evaluated in patients in whom no effective pharmacologic therapy could be determined in an electrophysiologic study (EPS). The study population consisted of 49 consecutive patients with sustained VT who were receiving long-term pharmacologic therapy despite the fact that no pharmacologic therapy had been found to be effective in the EPS. The efficacy of the pharmacologic therapies was assessed by HM. A reduction in frequent (10/h) premature ventricular contractions (PVCs) was used as an index of treatment efficacy, with therapies achieving substantial PVC suppression (>70% of all PVCs) being considered to be effective (HM effective group). When no therapy was found to be effective when assessed by HM, a drug with any other beneficial effect, eg, reduction in VT rate, was chosen (HM ineffective group). VT recurrence and survival were compared between groups. During the follow-up period of 31+/-28 months, VT recurrence was observed in a total of 25/49 patients: 3/17 patients in the HM effective group, in 18/25 in the HM ineffective group, and in 4/7 in the HM undetermined group (p=0.0487). Sudden cardiac death occurred in a total 7/49 patients: 2/17 patients in the HM effective group, 4/25 patients in the HM ineffective group, and 1/7 patient in the HM undetermined group (p=0.2828). Among patients in whom no effective therapy could be determined by EPS, the VT recurrence rate was significantly lower in the group in whom treatment was effective as assessed by HM than among those in whom treatment was assessed by HM to be ineffective. Sudden cardiac death rate was also lowest in the HM effective group, although the difference was not statistically significant. HM assessment was considered useful in selection of pharmacologic therapy for patients in whom no effective therapy could be determined in the EPS.

Repetitive ventricular responses induced by radiofrequency ablation for idiopathic ventricular tachycardia originating from the outflow tract of the right ventricle.

In 23 consecutive patients, radiofrequency (RF) ablation was used as treatment for idiopathic ventricular tachycardia (VT) originating from the outflow tract of the right ventricle. In this study, we focused on the repetitive ventricular response (> 5 consecutive QRS beats during RF application). The incidence and clinical implications of the repetitive ventricular response were examined through the results of endocardial mapping and RF ablation. VT origin was mapped as the earliest activation site during VT, and it was determined within 0.5 x 0.5 cm (narrow site) in 13 patients and wider than 0.5 x 0.5 cm (wide origin) in the other 10 patients. The repetitive ventricular response was induced during application of RF current in 14 of 23 patients (61%), and it was more frequently observed in VT from a wide origin (100%) than in the VT from a narrow site (31%). The QRS morphology of the repetitive ventricular response was identical to that of clinical VT. As RF application was continued and/or repeated, the RR interval of the repetitive ventricular response was gradually prolonged, the number of consecutive QRS complexes was decreased, and clinical VT was finally eliminated. The overall success rate of RF ablation was 96% (22/23 patients), and no complications were observed. In conclusion, a repetitive ventricular response was frequently observed in idiopathic right VT. The changing pattern of repetitive ventricular response, slowly and/or disappearing was consistent with successful RF ablation.

Relation between bradycardia dependent long QT syndrome and QT prolongation by disopyramide in humans.

BACKGROUND: Recent molecular biological investigations have identified abnormal genes in familial forms of long QT syndrome, but in bradycardia dependent acquired long QT syndrome, no such genetic abnormality has yet been identified. OBJECTIVE: To investigate the relation between the responses of QT interval to pacing change and to disopyramide. METHODS: This study included 13 patients with bradyarrhythmia who had undergone pacemaker implantation. The patients were divided into two groups: group I (n = 8), patients with QT prolongation (QT interval > or = 500 ms) during bradycardia; group II (n = 5), patients without QT prolongation (QT interval < 500 ms) during bradycardia. The responses of QT interval caused by the change of pacing rate were determined and compared with the changes of the QT interval after disopyramide administration. RESULTS: The QT interval in group I was significantly longer than that in group II when the pacing rate was decreased from 110 to 50 beats/min: mean (SD) 451 (16) v 416 (17) ms at 90 beats/min (p = 0.0033), and 490 (19) v 432 (18) ms at 70 beats/min (p = 0.0002), respectively. The QT interval was prolonged significantly by disopyramide in both groups, but the change was more pronounced in group I than in group II: 78 (33) v 35 (10) ms (p < 0.05). CONCLUSIONS: This study suggests that the patients showing bradycardia dependent QT prolongation are also more markedly affected by disopyramide and that abnormal potassium channel may be the underlying mechanism.

Coronary artery perforation with subepicardial hematoma.

Coronary artery perforation is a relatively rare complication in coronary angioplasty. We report the case of a 71-year-old male, who was salvaged by emergency surgery, for cardiogenic shock due to subepicardial hematoma associated with balloon angioplasty. Such a case has not yet previously been reported.

Preferential action of mexiletine on central common pathway of reentrant ventricular tachycardia.

OBJECTIVES: The action of mexiletine on diseased myocardium was assessed in reentrant ventricular tachycardia (VT). BACKGROUND: Whether class Ib antiarrhythmic agents exert a preferential action on the central common pathway of reentrant ventricular tachycardia has not yet been studied in humans. METHODS: In 10 consecutive patients (7 with a previous myocardial infarction, 3 with nonischemic disease), VT was induced and entrained with rapid pacing. The orthodromic conduction time was measured from stimulus to the entrained electrogram at the exit from the presumed central common pathway (i.e., the earliest site of activation). Mexiletine at 125 to 250 mg was administered intravenously, and when VT with the same configuration was induced, the study was repeated. The action of mexiletine on the central common pathway was assessed from the changes in VT cycle length and orthodromic conduction time. The effects on QRS complex duration, local conduction time between the exit and the pacing site and duration of the local electrogram were compared between normal and diseased myocardium. RESULTS: Mexiletine prolonged the VT cycle length in all patients, from (mean +/- SD) 316 +/- 30 to 360 +/- 64 ms (mean change 20 +/- 7%, p < 0.001); during entrainment of VT, the orthodromic conduction time was prolonged, from 306 +/- 58 to 367 +/- 89 ms (mean change 18 +/- 9%, p < 0.001). These changes were highly correlated (r = 0.95, p < 0.001). QRS duration changed little (4 +/- 3%), and local conduction time showed no change. The duration of the fragmented electrogram width was prolonged by mexiletine: from 146 +/- 50 to 176 +/- 56 ms (mean change 23 +/- 8% during VT, p < 0.001). Only a slight change occurred in the effective refractory period, both at the pacing site and at the exit. CONCLUSIONS: Mexiletine caused little change in conduction time in normal myocardium but prolonged VT cycle length, orthodromic conduction time and duration of the local electrogram at the earliest site of activation of VT. From these findings, a preferential action of mexiletine on diseased myocardium was suggested but seemed to occur only at higher frequencies during tachycardia.