Discrepant effects of mexiletine on cycle length of ventricular tachycardia and on the effective refractory period in the area of slow conduction.

OBJECTIVE: Monomorphic sustained ventricular tachycardia (VT) can often be entrained and interrupted at a critical paced cycle length. The aim was to evaluate a possible determinant of this phenomenon by observing the action of mexiletine on the critical paced cycle length and other variables. METHODS: Nine consecutive patients with symptomatic VT were studied. After induction of VT, the area of slow conduction was mapped as the earliest site of the activation or the site with mid-diastolic potential during the tachycardia. Rapid pacing was performed at a site distant from the tachycardia circuit to entrain the tachycardia, starting at a cycle length 10-20 ms shorter than the VT cycle length, and repeated after a decrement of the cycle length in steps of 10 ms to obtain the longest paced cycle length that interrupted the tachycardia: the block cycle length. The effective refractory period (ERP) was measured at the pacing site at which the myocardium was presumed to be normal and also in the area of slow conduction. The effects of mexiletine on the cycle length of VT, the block cycle length, and the ERP at two sites were obtained before and after mexiletine administration. The relation between the cycle length of VT and block cycle length and their changes were also analysed. RESULTS: 11 VTs with the same morphology were induced before and after mexiletine administration. The VT cycle length was prolonged by mexiletine from 309 (SD 53) to 361 (47) ms, and it was interrupted at block cycle lengths of 247 (37) and 307 (41) ms, respectively, the changes being 18 (12)% and 23 (8)% (both P < 0.001). All VTs were entrained, and during pacing at the block cycle length there was abrupt loss of fusion and change in the presystolic electrogram, always associated with interruption of VT on cessation of rapid pacing. A good correlation was observed between the VT cycle length and the block cycle length (r = 0.77 to 0.80). The ERP at the pacing site (normal myocardium) and in the area of slow conduction showed no significant change: 241 (21) v 240 (22) ms and 262 (9) v 252 (9) ms, respectively. The block cycle length was longer than the ERP after mexiletine administration: 362 (55) v 252 (9) ms (P < 0.02). CONCLUSIONS: Mexiletine prolonged the cycle length of VT and the VT-interrupting critical cycle length but not the ERP. The prolongation of the VT cycle length and the block cycle length by mexiletine seemed to be unrelated to the action potential duration, but related to depressed intercellular conduction.     

Inappropriate discharges from an intravenous implantable cardioverter defibrillator due to T-wave oversensing.

This report describes the clinical management of 2 patients with ventricular fibrillation (VF) who received inappropriate shocks from an implantable cardioverter defibrillator (ICD) due to T-wave oversensing. Cardiac sarcoidosis was confirmed as the underlying heart disease in 1 patient and idiopathic dilated cardiomyopathy in the other. Within 2 months after ICD implantation, both patients received several inappropriate shocks during sinus rhythm. Stored electrograms showed decreased R-wave amplitudes and increased T-wave amplitudes. The ICD sensed both R- and T-waves as ventricular activation, which met the rate criteria for VF treatment. Reprogramming the sensing threshold in association with administration of a drug to slow the heart rate decreased the incidence of the inappropriate shocks in both patients, but these palliative measures did not completely suppress the inappropriate shocks. To avoid T-wave oversensing, the repositioning or adding of a sensing lead is required. The potential risk of T-wave oversensing in ICD patients who have small R-wave amplitudes should be recognized.     

Radiofrequency catheter ablation for idiopathic right ventricular tachycardia with special reference to morphological variation and long-term outcome.

OBJECTIVE: To assess the long term outcome of radiofrequency (RF) catheter ablation for idiopathic ventricular tachycardia (VT) originating from the outflow tract of the right ventricle, with special reference to the morphological variation in the VT-QRS complexes. PATIENTS: 13 patients whose ventricular tachycardia was treated with RF ablation were followed up more than 18 months after RF ablation. RESULTS: Endocardial mapping revealed the various extensions of ventricular tachycardia origin (from 0.5 x 0.5 cm to 2.0 x 2.0 cm) in which the earliest local electrogram was recorded during ventricular tachycardia. In all five tachycardias from a relatively wider origin (more than 0.5 x 0.5 cm) and in four of eight from a narrow origin (< 0.5 x 0.5 cm), subtle morphological variation in the VT-QRS complexes was observed. In tachycardias with morphological variation, the local electrogram at the tachycardia origin also showed concomitant variation in morphology and activation sequence. Ventricular tachycardia from a narrow site was eliminated by RF ablation to the confined site, but a larger number of RF applications was required in tachycardias from a wider origin. All 13 tachycardias were successfully ablated by RF current, and during the follow up period of 28.2 (SD 7.2) months, recurrence was observed in only one patient who had a wider origin. CONCLUSIONS: Long term efficacy of RF ablation was excellent in idiopathic ventricular tachycardia originating from the outflow tract of the right ventricle. Subtle morphological variations were frequently observed in this type of ventricular tachycardia, and about half of them represented a relatively wider arrhythmogenic area.     

Aortitis syndrome, coronary artery ectasia, and mid-ventricular obstruction

A 46-year-old Japanese woman, who had been diagnosed as having aortitis syndrome 4 years earlier, was admitted to our hospital in May 1989. The diagnosis of aortitis syndrome was confirmed by intravenous digital subtraction angiography which showed stenotic lesions in each subclavian artery, the left common carotid artery, and the descending aorta. Coronary arteriography revealed diffuse and prominent dilatation of entire coronary artery segments. Moreover, a left ventriculogram showed complete obstruction of the mid-ventricle during systole. Thus, we diagnosed this case as aortitis syndrome complicated by coronary artery ectasia and mid-ventricular obstruction. The causal relations of these findings are discussed.     

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.     

Diurnal variation in QT dispersion in patients with chronic heart failure

QT dispersion is defined as the difference in QT interval among the different leads of the standard 12-lead electrocardiogram and reflects inhomogeneity of myocardial repolarization. Dispersion of repolarization is an important electrophysiologic feature that is considered fundamental for the initiation of ventricular fibrillation. However, no data exist regarding the diurnal variation of QT dispersion measured from simultaneous 12-lead recording in chronic heart failure patients. The aim of this study was to identify diurnal variation in QT dispersion in patients with chronic heart failure. QT dispersion was measured in the 12-lead standard electrocardiogram in 11 patients with chronic heart failure. QT dispersion in these patients was increased in the afternoon compared to the morning. It is concluded that QT dispersion has a clear diurnal variation in patients with chronic heart failure. These findings have potentially significant implications for therapy and prevention of sudden cardiac death in patients with chronic heart failure.     

Epicardial and endocardial mapping determine most successful site of ablation for ventricular tachyarrhythmias originating from left ventricular summit

A 34-year-old woman presented with idiopathic premature ventricular complex (PVC) and ventricular tachycardia (VT) originating from the area called the left ventricular summit. Radiofrequency (RF) application both through the coronary sinus and to the epicardial surface transiently suppressed the VT/PVC. Radiofrequency with sufficient energy was only applicable from the endocardial site, and the VT/PVC was successfully eliminated.     

Glycine and <Emphasis Type="SmallCaps">d</Emphasis>-serine,but not <Emphasis Type="SmallCaps">d</Emphasis>-cycloserine,attenuate prepulse inhibition deficits induced by NMDA receptor antagonist MK-801

RATIONALE: Several agents that stimulate the glycine site of N-methyl-D: -aspartate (NMDA) receptors have been reported to moderately improve both negative symptoms and cognitive dysfunctions in patients with schizophrenia. However, differences in efficacy have also been reported, and further comparative pharmacological studies are still needed. OBJECTIVES: We aimed to explore the effects of two glycine site agonists of the NMDA receptor, glycine and D: -serine, and a partial agonist, D: -cycloserine, on prepulse inhibition (PPI) deficits induced by a NMDA receptor antagonist, MK-801, in mice. Furthermore, we performed in vivo microdialysis and additional PPI measurements using a selective glycine site antagonist to verify if the beneficial effects observed after the systemic administration of glycine were due to glycine itself via its activity at the glycine site. RESULTS: High doses of glycine (1.6 g/kg) and D: -serine (1.8 and 2.7 g/kg) significantly attenuated MK-801-induced PPI deficits. In contrast, D: -cycloserine did not show any amelioration of MK-801-induced PPI deficits at doses ranging from 7.5 mg/kg to 60 mg/kg. The selective glycine site antagonist, L-701,324 (10 mg/kg), antagonized the effect of glycine on MK-801-induced PPI deficits. Furthermore, in vivo microdialysis demonstrated that intraperitoneal injection of glycine significantly increased glycine and L: -serine levels, but decreased D: -serine levels in the prefrontal cortex. CONCLUSIONS: The findings of the present study suggest that glycine and D: -serine but not D: -cycloserine could attenuate PPI deficits associated with NMDA receptor hypofunction via NMDA glycine sites in the brain.