Catheter ablation of ventricular tachycardia with radiofrequency currents, with special reference to the termination and minor morphologic change of reinduced ventricular tachycardia.

During catheter ablation with radiofrequency (RF) currents, the incidence of the termination of reentrant ventricular tachycardia (VT) during application of RF energy and the morphologic change of the reinduced VT were analyzed. Twenty-five patients (20 men and 5 women, aged 44 +/- 17 years) were studied. After induction of monomorphic sustained VT, the ablation site was determined by endocardial activation mapping, identification of isolated mid-diastolic potential, and pacing during tachycardia. Thirty-six monomorphic VTs were induced in 25 patients and terminated with programmed stimulation. The cycle length was 323 +/- 55 ms and all VTs were entrained with rapid ventricular pacing. The target site was the earliest site of activation of VT in 26 VTs in 16 patients, and the area of slow conduction in 10 VTs in 9 patients. VT was terminated soon after the application of RF currents in 33 VTs in 22 patients at 6.0 +/- 3.1 seconds, and VT was induced immediately after the cessation of RF currents in 11 patients. Of these, 4 patients with idiopathic left ventricular VT had an alternation in the QRS configuration before catheter ablation and required repeat ablation of the other VT morphology. In the other 7 patients, such morphology was not observed before ablation, but was observed in VT induced when the original VT was terminated. Repeated attempts of catheter ablation 2 to 9 times at the remapped site was, however, successful in 7 of 8 VTs.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency of presumed reentry with an excitable gap in sustained ventricular tachycardia unassociated with coronary artery disease.

In sustained ventricular tachycardia (VT) unrelated to coronary artery disease, the incidence of reentry with an excitable gap was examined, and rapid pacing was performed to entrain VT in 48 episodes in 42 consecutive patients. Coronary artery disease was excluded by coronary arteriography. The underlying heart diseases were postoperative congenital heart diseases (n = 5), dilated (n = 7) or hypertrophic (n = 4) cardiomyopathy, arrhythmogenic right ventricular dysplasia (n = 6) and miscellaneous heart diseases (n = 5), as well as no demonstrable heart disease (n = 15) in which 8 patients had verapamil-responsive VT. Except for 1 patient with hypertrophic cardiomyopathy, 48 morphologically distinct monomorphic sustained VTs were induced. Twenty-five VTs showed right bundle branch block morphology and 23 left bundle branch block morphology, and VT was entrained in 84 and 96%, respectively. The overall incidence of the entrainment was 89.6% (43 of 48 monomorphic VTs), and the frequency of the ability to entrain VT ranged between 33.3 and 100% in the subgroups. The lowest frequency was found in hypertrophic cardiomyopathy. In conclusion, most inducible monomorphic sustained VT unassociated with coronary artery disease was presumed to be reentry with an excitable gap.

Drug-induced narrowing of the width of the zone of entrainment as a predictor of the subsequent non-inducibility of reentrant ventricular tachycardia after an additional dose of an antiarrhythmic drug.

BACKGROUND: The efficacy of drugs used to treat inducible monomorphic sustained ventricular tachycardia (VT) has been assessed by investigating their ability to suppress inducibility, but the mechanism of the drug action remains to be determined. OBJECTIVES: To determine electrophysiological variables that predict inducibility, divided doses of class I antiarrhythmic drugs were given and their effects were analysed, particularly the ability of the final dose to suppress inducibility. METHODS: The excitable gap was estimated by the zone of entrainment, which was defined as the difference between the cycle length of VT and the longest paced cycle length that interrupted VT during entrainment of VT with rapid pacing at paced cycle lengths in decrements of 10 ms. The cycle length of VT, the block cycle length, and the zone of entrainment were measured in the drug free state and after intermediate and final doses of procainamide, disopyramide, cibenzoline, and mexiletine. RESULTS: Sustained monomorphic VT with a mean (SD) cycle length of 285 (43) ms was induced in 8 patients. It was entrained and interrupted at the block cycle length of 231 (31) ms. The width of the zone of entrainment was 54 (23) ms. In 8 studies VT was not inducible at final doses of procainamide in 4, cibenzoline in 1, and mexiletine in 3. In another 10 studies (procainamide in 4, disopyramide in 1, cibenzoline in 2, and mexiletine in 3), VT remained inducible at the intermediate dose and at the final dose. The cycle length of VT was prolonged to a similar degree in studies of effective and ineffective drugs, but the cycle length that blocked VT was longer at the intermediate dose of the effective drugs. Consequently, the width of the zone of entrainment was significantly narrowed at the intermediate dose of effective drugs and the width of the zone of entrainment was narrower than when ineffective drugs were given (22 (13) ms v 76 (18) or 75 (37) ms at the intermediate and final doses respectively (P < 0.02). CONCLUSION: Drugs that narrowed the zone of entrainment were associated with non-inducibility of VT after the final dose of the drug was given. The baseline variables did not predict the responses to class I antiarrhythmic drugs.

A comparison of electrophysiologic properties between responders and non-responders to DL-sotalol among patients with ventricular tachyarrhythmia. Importance of the lack of a reverse use-dependent effect on ventricular refractoriness to responders.

This study was undertaken to determine whether dl-sotalol can prevent ventricular tachyarrhythmia inducibility that can be predicted from electrophysiologic parameters. The effects of dl-sotalol in 16 patients (ventricular tachycardia (VT) in 11 and fibrillation (VF) in 5) were determined in electrophysiologic studies before and after dl-sotalol (320 mg/day). In 9 of 16 patients (56%) after dl-sotalol, ventricular tachyarrhythmia could not be induced by the entire stimulation protocol (responders). There were significant differences in QT interval (462 +/- 52 vs. 415 +/- 34 msec; p < 0.05) and ventricular effective refractory period (VERP) at 600, 400 and 300 msec (302 +/- 28 vs. 262 +/- 20 msec; p < 0.001, 280 +/- 23 vs. 240 +/- 21 msec; p < 0.001, 256 +/- 24 vs. 222 +/- 12 msec; p < 0.005, respectively) between responders and non-responders. The percentile increases in VERP (% VERP) at 600, 400, and 300 msec in responders were 25%, 26%, and 27%, whereas those in non-responders was 9%, 7%, and 7%, respectively. Isoproterenol administered to responders did not fully reverse the dl-sotalol-induced prolongation of VERP (delta VERP) at 600, 400, and 300 msec, which remained significantly prolonged compared to the baseline (281 +/- 18 vs. 241 +/- 16 msec; p < 0.01, 258 +/- 20 vs. 223 +/- 21 msec; p < 0.01, 247 +/- 22 vs. 202 +/- 16 msec; p < 0.01, respectively). % VERP did not exhibit significant differences at 600 (16%), 400 (15%), and 300 (20%) msec, indicating the lack of a reverse use-dependency. The results suggest that delta VERP in responders did not show reverse use-dependency, and that the phenomenon may account for the efficacy of dl-sotalol.

Effects of class I and III antiarrhythmic drugs on ventricular tachycardia-interrupting critical paced cycle length with rapid pacing.

The most common mechanism of sustained ventricular tachycardia (VT) is re-entry with an excitable gap, but the electrophysiologic properties and response to antiarrhythmic drugs in the area of slow conduction are not yet fully known. The purpose of this study was to assess the effects of a class I antiarrhythmic drug (procainamide) and class III agents (amiodarone, E-4031, and MS-551) on re-entrant VT using the width of the zone of entrainment. The cycle length (CL) of VT (VTCL), the block CL that was the longest paced CL that interrupted the VT, and the width of the zone of entrainment, defined as the difference between VTCL and block CL, were compared before and after treatment with antiarrhythmic drugs. The VTCL was prolonged significantly from 308+/-63 to 410+/-77 msec after procainamide (p<0.005) but was not changed after the administration of the class III agents: from 294+/-50 to 292+/-13 msec after amiodarone, and from 305+/-47 to 313+/-31 msec after E-4031 or MS-551 (p=NS). The block CL was prolonged from 255+/-61 to 331+/-70 msec after procainamide (p <0.01), from 256+/-20 to 260+/-25 msec after amiodarone, and unchanged after E-4031 or MS-551 (253+/-31 msec before and 270+/-43 msec after) (p=NS). The width of the zone of entrainment as a representative of the width of the excitable gap was changed from 52+/-26 to 79+/-35 msec (p<0.05) after procainamide, whereas it was unchanged after amiodarone (48+/-7 msec before and 43+/-7 msec after) and after E-4031 or MS-551 (50+/-10 msec before and 40+/-9 msec after). Therefore, amiodarone, E-4031, and MS-551 did not affect VTCL and block CL whereas procainamide increased these parameters. The excitable gap substituting as the zone of entrainment was increased by procainamide but slightly reduced by amiodarone, E-4031, and MS-551. The effects of these antiarrhythmic drugs on the excitable gap of re-entrant VT were variable and should be examined further.

Chemical modification of a catalytic antibody that accelerates the hydrolysis of carbonate esters.

Catalytic antibody, 4A1, catalyzes the hydrolysis of p-nitrophenyl alkyl carbonate. To determine the amino acid residues related to the catalytic activity of the antibody, we studied the effect of Tyr-, Trp-, and Lys-selective reagents on the catalytic activity and determined the amino acid sequences around the modified amino acid residues. We found that the Tyr-selective reagent is the most effective one and the modification of one Tyr residue results in the complete loss of the catalytic activity. The modified Tyr residue is identified to be Tyr-32 in the CDR-1 of the L chain.

Procainamide-induced changes in reentrant ventricular tachycardia with special reference to the tachycardia-interrupting critical paced cycle length during transient entrainment with rapid pacing.

With rapid ventricular pacing, sustained ventricular tachycardia (VT) is often entrained and interrupted at a critical paced cycle length. In this paper, the possible mechanism and determinant of the critical cycle length interrupting VT are addressed. Sixteen consecutive patients underwent rapid ventricular pacing in 18 morphologically distinct sustained VTs before and after procainamide. The VT morphology was identical before and after the drug. The VT origin was determined by endocardial mapping as the earliest site of activation of VT and an electrode catheter was located at the site. Rapid pacing was performed to entrain VT and repeated in 10 msec decrements of cycle length until VT was interrupted at a critical paced cycle length which was defined as the block cycle length. The effective refractory period was measured at the pacing site. The paced QRS duration and the local conduction time were measured and used as indices of conduction time in the normal myocardium. VT was entrained and interrupted in all patients. At the block cycle length, initial constant fusion was replaced abruptly by the fully paced QRS complex. At the same time, the local electrogram at the site of VT origin showed changes in the morphology and the timing of activation which were identical to those of the fully paced beat. This loss of fusion and the changes in the local electrogram were considered to be a result of orthodromic block and the block cycle length was assumed to represent the cycle length at which 1:1 conduction fails in the area of slow conduction. After procainamide, both the VT cycle length and the block cycle length were prolonged to a similar degree (p < 0.001) but the relative degree of change varied from patient to patient. The paced QRS duration and the conduction time were prolonged by procainamide but in smaller degrees than the cycle length of VT or the block cycle length (p < 0.02-01). The effective refractory period at the pacing site and the QT interval showed small changes after procainamide. The postrepolarization refractoriness rather than the duration of action potential can be responsible for the procainamide-induced prolongation of the block cycle length, and the block cycle length might be used as a new index to characterize the electrophysiologic property of the VT circuit and also the action of antiarrhythmic drugs.

Pleomorphic ventricular tachycardia arising from a new site during antiarrhythmic drug therapy.

UNLABELLED: We analyzed the site of VT origin and the induction mode of VT in 9 patients who showed new VT morphologies with different bundle branch block patterns after administering antiarrhythmic drug(s). In all patients, VT exhibiting the clinical morphology was induced in the drug free state. (1) VT origin: In 6 patients, VTs showing LBBB pattern had a site of origin at the right ventricular free wall, and VTs with RBBB pattern originated from the left ventricular free wall. VT from the intraventricular septum of the right ventricle showed RBBB pattern in two patients and VT with LBBB pattern arose from the posteroseptum of the left ventricle in one patient. (2) VTs with new morphologies: After administering drug(s), VTs with new morphologies were induced in 18 studies and the mean cycle length of these VTs was not different from that in the control study. Among them, the induction mode was less aggressive in 4 of 7 drug studies and more aggressive in 1 study. (3) VTs with the same morphology: VTs with morphologies identical to those of the clinical VTs were induced in 15 studies. However, the drugs' effect was evident. The mean cycle length of these VTs was significantly prolonged, and VTs were induced by less aggressive modes or at longer coupling intervals. IN CONCLUSION: (1) After administering drug(s), different electrophysiologic characteristics were observed between the VTs with new morphologies and the VTs with the same morphology. (2) If a new VT was induced by less aggressive modes after administering drug(s), the drug(s) might act to facilitate inducibility: proarrhythmic effect.

Electrophysiological findings in idiopathic recurrent ventricular fibrillation: special reference to mode of induction, drug testing, and long-term outcomes.

Electrophysiological studies can be useful in the presence of idiopathic ventricular fibrillation (VF) and may be used when selecting antiarrhythmic drugs. However, the yield, the mode, and the long-term reproducibility of the induction of VF have not yet been fully elucidated. Eight patients with idiopathic VF underwent electrophysiological study. The mean age (+/- SD) was 45 +/- 17 years. Six were males and two were females. Diagnosis was done by exclusion. VF was induced in 6 (75%) of 8 patients using double extra stimuli at coupling intervals of 233 +/- 39 and 191 +/- 20 ms for the first and second extra stimuli, respectively. Of note, VF was induced by stimulation exclusively at the origin of the premature ventricular beat, which was the first complex of VF in two patients. In another patient, VF was initiated by two premature stimuli and also by a pause produced by rapid pacing. The inducibility of VF was reproduced 9-18 months after the first induction in all of the four patients studied. When the ability of antiarrhythmic drugs to suppress VF inducibility was confirmed, no recurrence was observed during the follow-up period of 40-160 months, but a recurrence of VF was observed in one of two nonresponders. In one patient, amiodarone administration failed in preventing VF induction 9 months after initiation of therapy, and reassessment of long-term drug-efficacy might be indicated in some patients. In conclusion, idiopathic VF was highly inducible (75%) with double extra stimuli. In this study, it was induced from a specific site (2/8) or by a pause (1/8). Induction of VF seemed to be reproduced 9-18 months after the first study. The outcome was considered favorable when the inducibility of VF was suppressed by antiarrhythmic drugs.

Procainamide induced change of the width of the zone of entrainment and its relation to the inducibility of reentrant ventricular tachycardia.

Procainamide depresses conduction velocity and prolongs refractoriness in myocardium responsible for reentrant VT, but the mechanism by which the induction of VT is suppressed after procainamide administration remains to be determined. In the present study, the relationship between electrophysiological parameters and the noninducibility of VT was assessed during procainamide therapy with a special reference to the change of an excitable gap. Clinically documented monomorphic sustained VT was induced in 30 patients and, utilizing the phenomenon of transient entrainment, the zone of entrainment was measured as the difference between the cycle length of VT and the longest paced cycle length interrupting VT (block cycle length) which was determined as the paced cycle length decreased in steps of 10 ms, and used as an index of the excitable gap. The effective refractory period was measured at the pacing site and the paced QRS duration was used as an index of the global conduction time in the ventricle. The cycle length of VT, the block cycle length, and the width of the zone of entrainment were determined and compared between the responders and nonresponders. In 15 patients, these parameters were determined at the intermediate dose and related to subsequent noninducibility at the final dose. At the final doses of procainamide, VT was suppressed in 8 (26.7%) of 30 patients. However, the cycle length of VT, the block cycle length, and the width of the zone of entrainment were unable to predict the drug efficacy, i.e., noninducibility. The change in the effective refractory period at the pacing site or the width of the paced QRS duration was not different between the responders and nonresponders. Among the variables, only the width of the zone of entrainment showed a significant narrowing in the responders at the intermediate dose of procainamide, and it was smaller than that of the nonresponders. The significant narrowing of the width of the zone of entrainment was associated with the subsequent noninducibility of VT at the final dose. The present study showed that the baseline cycle length of VT, the block cycle length, the drug induced change of the effective refractory period, or the paced QRS duration was not a predictor of the noninducibility after procainamide administration. However, a significant narrowing of the width of the zone of entrainment at the intermediate dose was associated with the noninducibility of VT at the final dose.

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.

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.

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.

Comparative electrophysiologic findings between responders and nonresponders to class III antiarrhythmic drugs among patients with ventricular tachyarrhythmia.

Electrophysiologic testing was performed in 31 patients with ventricular tachycardia (21 cases) and fibrillation (10 cases) to characterize the electrophysiologic properties of patients responding or not responding to therapy with class III antiarrhythmic drugs. At the baseline, there were no differences among the patients in the monomorphic VT cycle length (CL), block CL or the width of the zone of entrainment. Ventricular tachyarrhythmias after the administration of class III drugs (sotalol: 9, amiodarone: 15 and E-4031/MS-551: 7) were inducible (non-responders) in 17 patients and non-inducible (responders) in 14 (45%). The class III drugs prolonged the sinus cycle length (SCL), QT interval and right ventricular effective refractory period (VERP), but had little effect on ventricular conduction time in the responders and non-responders. The SCL, QT interval and VERP at the three drive cycle lengths of 600, 400 and 300 msec were significantly longer in the responders than in the non-responders, but the class III drug action on VERP showed a reverse use-dependency. Isoproterenol administered to the responder did not fully reverse the class III antiarrhythmic drug-induced prolongation of QT, QTc and VERP, which remained significantly prolonged compared to the baseline values. Furthermore, when the VERP after the administration of class III drugs were greater than 270, 250 and 240 msec at the three drive cycle lengths of 600, 400 and 300 msec, respectively, it was associated with the non-inducibility of VT/VF. Though the precise mechanism of the drug efficacy is not yet known, these observations help to clarify the ability of class III drugs to prevent the induction of ventricular tachyarrhythmia.

Entrainment of ventricular tachycardia in arrhythmogenic right ventricular tachycardia.

In two patients with arrhythmogenic right ventricular dysplasia (ARVD), sustained ventricular tachycardia (VT) was induced by programmed stimulations during serial drug testings. One patient had five and the other had two VT morphologies, and the sites of origin were determined by endocardial catheter mappings. When overdrive pacing was performed, constant fusion in the QRS complex was observed in the two patients. Constant fusion of a different degree was also observed at different paced cycle lengths. Both patients had dilated right ventricles and wall-motion abnormality, and the diagnosis of ARVD was further confirmed by the specimen resected at the site of origin of VT. Therefore, VT in ARVD can be entrained and reentry is the most likely mechanism of such VT.

Catheter ablation with radiofrequency current of ventricular tachycardia originating from the right ventricle.

Catheter ablation of ventricular tachycardia (VT) with radiofrequency current would be safer than the conventional ablation with direct current shocks. Seven patients who had eight morphologically distinct symptomatic monomorphic VTs underwent catheter ablation with radiofrequency current. The mean age +/- SD was 52 +/- 16 years, and the mean cycle length of the clinical VT was 298 +/- 36 milliseconds. Sustained VT was induced by programmed stimulation with or without isoproterenol in four patients and developed during the infusion of isoproterenol alone in two patients. Of these, four VTs were entrained with rapid pacing. The ablation was attempted at the site of earliest activation through the distal electrode and the external patch electrode on the back during VT in seven episodes in six patients. In the other patient it was applied during sinus rhythm. Energy was 40 to 50 W in the first case and 30 to 40 W in the others, and was given for 30 seconds. All VTs were terminated within 6 seconds, 3.6 +/- 0.8 seconds after the application of the radiofrequency current. Additional current was given to one to four predetermined sites by mapping. The mean number of applications was 4.0 +/- 1.3 sites. Except in the first patient, VT was eliminated successfully and VT was not induced by programmed stimulation, by the administration of isoproterenol, or by treadmill exercise testing. VT did not recur during the follow-up period of 6.8 +/- 1.1 months.

Two cases of ventricular parasystole associated with ventricular tachycardia.

In two patients, ventricular parasystole (VP) was associated with ventricular tachycardia (VT), and in one patient, catheter ablation was successful. In patient 1, with dilated cardiomyopathy, VP led to VT, which converted to ventricular fibrillation. In patient 2, VP led to symptomatic nonsustained polymorphic VT. The origin of parasystolic focus was determined by endocardial mapping, and a radiofrequency current was delivered to patient 2. Both VP and VT disappeared immediately, and no recurrence has been observed during a follow-up of 8 months. Catheter ablation to the parasystolic focus was effective and a relationship between VP and VT was strongly suggested.

Alternation of QRS morphology and effect of radiofrequency ablation in idiopathic ventricular tachycardia.

UNLABELLED: We performed electrophysiological studies in 13 patients with idiopathic VT and attempted radiofrequency (RF) catheter ablation in 4 of them. RESULTS: VT was induced by programmed stimulation in all patients and the mean cycle length was 363 +/- 58 msec. In 8 of 13 patients (62%), alternation of either the cycle length and/or morphology of VT was observed. Transient entrainment was achieved in all patients by rapid pacing from the right ventricular outflow tract so reentry was considered the underlying mechanism of VT. The site of earliest activation (EAS) during VT was located at the apicoposterior portion of the left ventricular septum and used as the target site for RF catheter ablation. Spikelike presystolic activity was detected 20-40 msec prior to the large deflection of the local electrogram in four patients. VT was terminated by a few seconds of RF current in all four patients, but subsequently new VTs with a slightly different morphology were induced in three of them and re-mapping showed a shift of the EAS. After additional RF ablation at the new EAS, VT was no longer induced. No complication was noted and VT did not recur during a follow-up period for a mean of 9.3 +/- 5.2 months. CONCLUSION: RF catheter ablation seems useful and safe for idiopathic VT. The alternation of QRS morphology and the findings at the time of catheter ablation suggest that an alternative pathway or multiple exists may be present in some patients with idiopathic VT, because the change in VT morphology was associated with a shift of the EAS.

Alteration by maternal pinealectomy of fetal and neonatal melatonin and dopamine D1 receptor binding in the suprachiasmatic nuclei.

The effects of maternal melatonin on fetal and neonatal melatonin and dopamine D1 receptor systems in the central nervous system, mainly in the suprachiasmatic nuclei (SCN), were investigated after pinealectomy of rats at day 7 of pregnancy. 125I-labelled iodomelatonin injected intravenously into the pregnant rats (at day 21) was transferred in considerable amount into the fetal circulation. In vitro autoradiography data demonstrated an increase in the melatonin binding activity in the fetal (embryonic day 21) and early postnatal SCN (postnatal day 3) caused by maternal pinealectomy. This upregulation of the melatonin receptor in the SCN was then normalized after the melatonin system of the neonate started to work. The pregnant rats themselves did not show such a change in their melatonin receptors in the SCN following pinealectomy. Dopamine D1 receptor binding was affected by pinealectomy exclusively in the SCN of fetal and neonatal rats as well as in that of mothers. These results clearly indicate that the fetal circadian clock in the SCN is controlled and prepared before birth to some extent by maternal melatonin rhythm.