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rugada syndrome (BS) is characterized by ST-segment elevation in leads V1-3 with a right bundle branch block pattern and nocturnal sudden cardiac death caused by ventricular fibrillation (VF). 1,2 Patients with this syndrome who have experienced syncopal episodes or have been resuscitated from cardiac arrest have a poor prognosis if they do not receive an implantable cardioverter defibrillator (ICD). Although the prevalence of Brugada-type ECG change in healthy subjects is approximately 0.1-1%, their prognosis of is relatively good compared with symptomatic patients. 3-10 However, some asymptomatic patients become symptomatic and sudden cardiac death can occur with the first VF attack, so it is a problem in Japan of how to treat asymptomatic patients with a typical Brugada-type ECG who are detected by daily medical checkup. The results of some recent studies regarding the prognostic value of programmed electrical stimulation (PES) for patients with BS are conflicting; 6-9 Priori et al reported that the factors that predicted cardiac events were spontaneous ST elevation in leads V1-3 and episodes of syncope, but that VF inducible by PES did not indicate an increased risk of cardiac arrest, 7 whereas Brugada et al reported that induci-bility of ventricular arrhythmia and an abnormal ECG without provocation were predictors of arrhythmic events. 8,9 However, an electrophysiological study (EPS) is expensive and invasive, and sometimes results in complications, so it should not be carried out for all asymptomatic patients who show a Brugada-type ECG, but only for those patients for whom there is a high risk for a cardiac event. Because it is currently impossible to accurately predict the occurrence of cardiac events in asymptomatic patients, the present study was designed to determine noninvasive methods that could predict induction of VF by PES in asymptomatic patients with Brugada syndrome. For this purpose, the clinical characteristics of asymptomatic patients in whom VF was induced by PES were assessed, and the differences between the clinical values in asymptomatic patients with PES-induced VF and those without PES-induced VF were studied using noninvasive methods (a sodium channel blocker [pilsicainide] challenge test and a signal averaged electro-gram). Methods Patients The subjects of this study were 41 male asymptomatic patients with BS (age 27-66 years; mean age, 45±10 years). A Brugada-type ECG was defined as late r' wave (>0.2 mV) and ST segment elevation (>0.1 mV). 3 All of the subjects Circ J 2003; 67: 312-316 Ventricular fibrillation (VF) is induced in some asymptomatic patients with Brugada syndrome (BS), but the pro-gnostic value of programmed electrical stimulation (PES) in such patients is controversial. The clinical characteristics of 41 asymptomatic BS patients, divided into 2 groups according to whether VF was induced by PES (inducible VF group: n=13, non-inducible VF group: n=28) were evaluated. ST levels in the right precordial leads were measured before and after administration of pilsicainide...

1. To determine the biological effects of 23 polycyclic aromatic hydrocarbons (PAHs) and 3,4,3',4'-tetrachlorobiphenyl, the dose-response studies of the induction of CYP1-dependent xenobiotic oxidation activities by these chemicals in liver microsomes of C57BL/6J mice were studied. 2. In arylhydrocarbon-responsive C57BL/6J mice, the liver microsomal xenobiotic oxidation with substrates of 7-ethoxyresorufin, 7-ethoxycoumarin, (+/-)-benzo[a]pyrene-7,8-diol, dibenzo[a, pyrene-11,12-diol and 2-amino-3,5-dimethylimidazo[4,5-f]quinoline increased by increasing the doses of PAHs to mice, particularly when the PAHs that have been reported to be carcinogenic in experimental animals were used. In arylhydrocarbon receptor-knockout mice, there were no increases in liver microsomal 7-ethoxyresorufin O-deethylation activities nor in liver mRNA levels of CYP1A1, 1A2 and 1B1 by these chemicals. 3. Of the chemicals examined, benzo[k]fluoranthene, benzo[b]fluoranthene, benzo[j]-fluoranthene, 3-methylcholanthrene, dibenz[a,h]anthracene, dibenz[a,c]anthracene and 3,4,3',4'-tetrachlorobiphenyl were potent inducers of the induction of liver microsomal 7-ethoxyresorufin O-deethylation in mice. 4. Other PAHs such as 5-methylchrysene, benzo[a]pyrene, dibenzo[a,l]pyrene, dibenz[a,j]acridine, benzo[a]anthracene and 7,12-dimethylbenz[a]anthracene moderately induced 7-ethoxyresorufin O-deethylation activities in mice. PAHs reported to be weak or less carcinogenic in experimental animals did not induce the xenobiotic oxidation activities of CYP1A1 and 1B1 in the mice. 5. The results suggest that induction of liver microsomal CYP1-dependent xenobiotic oxidation activities is a good tool in determining the potencies of carcinogenic PAHs in arylhydrocarbon-responsive C57BL/6J mice.

IntroductionThe single nucleotide polymorphism (SNP) rs2106261 in the transcription factor gene ZFHX3 (16q22), a major regulator of inflammation, has been reported linking to atrial fibrillation (AF) by genome-wide association studies. Inflammation is known to be a strong predictor of atrial fibrillation recurrence after ablation, so we examined the association of the ZFHX3 SNP rs2106261 to inflammation marker expression and recurrence after AF ablation.MethodsWe genotyped ZFHX3 SNP rs2106261 and compared the minor (T) allele frequency between 362 paroxysmal AF (PAF) patients underwent pulmonary vein isolation (PVI) and 627 non-AF controls. We also analyzed associations between ZFHX3 SNP rs2106261 genotype and recurrence rate after pulmonary vein isolation and the inflammation markers.ResultsThe minor (T) allele frequency of the ZFHX3 SNP rs2106261 was significantly higher in AF patients than non-AF controls (odds ratio 1.52, p = 2.2×10−5). Multivariable analysis revealed that the minor allele (T) decreased AF recurrence rate after pulmonary vein isolation (hazard ratio 0.53, p = 0.04). Further, neutrophil/lymphocyte (N/L) ratio, C-reactive protein (CRP), and interleukin-6 (IL-6) expression levels were lower in PAF patients with the ZFHX3 SNP rs2106261 minor allele (TT+TC) than in CC patients (N/L ratio: CC 2.22 ± 0.08, TT+TC 1.98 ± 0.06, p = 0.018; CRP: CC 0.103 ± 0.009 mg/dl, TT+TC 0.076 ±0.007 mg/dl, p = 0.016; IL-6: CC 60.3 ± 3.0 pg/ml, TT+TC 52.8 ± 2.3 pg/ml, p = 0.04).ConclusionsThe ZFHX3 SNP rs2106261 minor allele is associated with lower AF recurrence rate after pulmonary vein isolation. Low baseline inflammation conferred by this allele may reduce AF recurrence risk.

Heart rate control during AF without sinus conversion may result in an incomplete cure of TIC, suggesting the advantages of rhythm control with ablation in patients with TIC.