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Journal of Cardiology 01/2013; · 1.28 Impact Factor
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ABSTRACT: Remodelling of the extracellular matrix (ECM) plays an important role in the production of arrhythmogenic substrate for atrial fibrillation (AF), and is considered to be promoted by the connective tissue growth factor (CTGF). Our objective was to assess the relationship between CTGF and ECM synthesis, and the effect of olmesartan on these processes.
Fifteen canine AF models were produced by rapid atrial stimulation. They were divided into three groups: pacing control (n = 5): 6-week pacing, pacing + olmesartan (n = 5): pacing with olmesartan (2 mg/kg/day), and non-pacing group (n = 5). In the pacing control group, messenger ribonucleic acid expressions of CTGF and collagen types 1 and 3 were up-regulated in comparison with the non-pacing group (P < 0.05) while transforming growth factor-β (TGF-β) did not exhibit a significant difference. In the pacing + olmesartan group, these up-regulations were suppressed (P < 0.05). In fluorescent immunostaining, the expression of CTGF was localized in the cytoplasm. The protein level of collagen type 3 was increased in the pacing control and it was suppressed in the pacing + olmesartan group.
CTGF and associated genes were up-regulated in the atria with the appearance of fibrosis. Because this up-regulation was independent of TGF-β and suppressed by olmesartan, CTGF up-regulation was considered to be mediated by angiotensin II.
Europace 03/2012; 14(8):1206-14. · 1.98 Impact Factor
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ABSTRACT: Although we have previously reported that the presence of paroxysmal atrial fibrillation (AF) is an independent risk factor for rehospitalization in patients with congestive heart failure (CHF) in a population from 1996 to 2002, the impact of AF configuration as a risk factor in a more recent population remains to be clarified.
319 patients with CHF admitted to our institute in 2006-2007 were retrospectively evaluated. The patients were divided into 3 groups in accordance with their basic cardiac rhythm, i.e. sinus rhythm (n=210), chronic AF (n=68), and paroxysmal AF (n=41). During the follow-up period of 19 ± 17 months, there was no significant difference in mortality or rehospitalization events among the 3 groups (p=0.542). In the multivariate analysis, no administration of β-blockers was the only independent risk factor for rehospitalization due to CHF exacerbation.
The clinical impact of AF configuration as a risk factor of rehospitalization due to CHF exacerbation was considered to be decreased in recent years.
Journal of Cardiology 03/2012; 60(1):36-41. · 1.28 Impact Factor
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ABSTRACT: Although the clinical benefits of implantable cardioverter-defibrillators (ICDs) have been demonstrated, inappropriate therapies (IATs) cannot be completely avoided even with the most advanced devices. Recently, IATs are considered to decrease the ventricular function and prognosis of a patient. The aim of this study was to investigate the predictors of IAT with parameters during cardiopulmonary exercise stress test (CPX). Sixty consecutive ICD patients underwent symptom-limited CPX, and were divided into IAT (+) and IAT (-) groups. During and after CPX, ECG and hemodynamic parameters of systemic blood pressure, heart rate, and maximal O(2 )consumption (max VO(2)) were evaluated every minute. In selected patients, sympathetic and parasympathetic activities were evaluated with analyses of heart rate variability (HRV). No significant differences were observed in clinical background parameters. In the CPX parameters, only the maximal heart rate exhibited a significant difference between the IAT (+) group and the IAT (-) group (154.8 ± 5.9 versus 137.9 ± 4.2 beats per minute, P = 0.032), and LF/HF was higher during the recovery phase 4 minutes after peak exercise in the former group (4.5 ± 1.0 versus 2.4 ± 0.9, P = 0.021). In ICD patients, IAT can be predicted using simple parameters of increased sympathetic activity such as increased maximal heart rate and increased LF/HF ratio during and after the exercise stress test.
International Heart Journal 01/2012; 53(5):276-81. · 1.16 Impact Factor
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ABSTRACT: Although oxidative stress is considered to promote arrhythmogenic substrates in diseased model animals, it is difficult to evaluate its primary role. In this study, we evaluated the promotion of arrhythmogenic substrates in the primary hyperoxidative state.
Sprague-Dawley rats were treated with L-buthionine-sulfoximine (BSO, 30 mmol · L(-1) · day(-1)) for 14 days. On day 7 or 14, the serum levels of derivatives of reactive oxygen metabolites (d-ROM) were measured, and immune staining of 8-hydroxy-2'-deoxyguanosine (8O HdG) was performed to assess oxidative stress. The ventricular effective refractory period (ERP), monophasic action potential duration (MAPD), and the inducibility of ventricular arrhythmia were also evaluated. BSO rats exhibited higher serum d-ROM and clearer 8OHdG staining than the controls. The inducibility of ventricular arrhythmia was higher in the BSO rats than in the controls. The ERP was shorter in the BSO rats than the control (day 14, 32 ± 1 vs. 36 ± 1 ms, P<0.05), whereas the MAPD(90) was longer in the BSO rats (day 14, 76 ± 5 vs. 55 ± 4 ms, P<0.05). The mRNA levels of Kv4.2, erg, and SERCA2a were downregulated in the BSO rats (P < 0.05), and Western blot analysis exhibited the downregulation of erg and SERCA2 expression in the BSO rats (P < 0.05).
Systemic oxidative stress might be one of the primary factors promoting cardiac electrophysiological remodeling and increasing the inducibility of arrhythmia independently of major organ disorders.
Circulation Journal 05/2011; 75(6):1386-93. · 3.77 Impact Factor
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ABSTRACT: Although bepridil is effective for conversion of long-lasting persistent atrial fibrillation (AF) to sinus rhythm, it sometimes takes a long time to interrupt AF and there is no feasible index to predict its efficacy.In 60 patients with long-lasting persistent AF, bepridil (100-200 mg/day) was administered and continued for 8 weeks while body surface ECG was recorded every 2 weeks. The fibrillation cycle length (FCL) was evaluated using the spectral analysis of the fibrillation waves in each ECG. AF was interrupted in 32 patients receiving bepridil. The conversion was observed at 2 weeks in 4, at 4 weeks in 7, at 6 weeks in 7, and at 8 weeks in 14 patients. When comparing these responders and nonresponders, clinical background characteristics other than the dosage of bepridil did not show any difference and neither did temporal changes in QT parameters and heart rate. In contrast, the FCL and ΔFCL (prolongation in FCL from baseline) became significantly larger in responders than in nonresponders at later observation points (FCL: 177 ± 17 versus 164 ± 19 ms, P = 0.018, and ΔFCL: 38 ± 16 versus 22 ± 12 ms, P < 0.001, at 4-week point; FCL: 188 ± 17 versus 169 ± 19 ms, P = 0.004, and ΔFCL: 49 ± 18 versus 27 ± 14 ms, P < 0.001, at 6-week point).Repetitive evaluation of FCL using spectral analysis of fibrillation waves can be a feasible index to predict the efficacy of bepridil therapy.
International Heart Journal 01/2011; 52(6):353-8. · 1.16 Impact Factor
