Masao Sakabe

University of Toyama, Тояма, Toyama, Japan

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Publications (49)208.7 Total impact

  • Akira Fujiki, Ryozo Yoshioka, Masao Sakabe
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    ABSTRACT: QT-RR linear regression consists of two parameters, slope and intercept, and the aim of this study was to evaluate repolarization dynamics using the QT-RR linear regression slope and intercept relationship during 24-h Holter ECG. This study included 466 healthy subjects (54.6 ± 14.6 years; 200 men and 266 women) and 17 patients with ventricular arrhythmias, consisted of 10 patients with idiopathic ventricular fibrillation (IVF) and 7 patients with torsades de pointes (TDP). QT and RR intervals were measured from ECG waves based on a 15-s averaged ECG during 24-h Holter recording using an automatic QT analyzing system. The QT interval dependence on the RR interval was analyzed using a linear regression line for each subject ([QT] = A[RR] + B; where A is the slope and B is the y-intercept). The slope of the QT-RR regression line in healthy subjects was significantly greater in women than in men (0.185 ± 0.036 vs. 0.161 ± 0.033, p < 0.001) and the intercept was significantly smaller in women than in men (0.229 ± 0.028 vs. 0.240 ± 0.027, p < 0.001). A scatter diagram of the QT-RR regression line slope and intercept among healthy subjects demonstrated a statistically significant negative correlation (B = -0.62A + 0.34, r = -0.79). Distribution of both scatter diagrams of the slope and the intercept of the QT-RR regression line in patients with IVF and TDP was different from healthy subjects (left corner for IVF and upward shift for TDP). The slope and intercept relationship of the QT-RR linear regression line based on 24-h Holter ECG may become a simple useful marker for abnormality of ventricular repolarization dynamics.
    Heart and Vessels 01/2014; · 2.13 Impact Factor
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    ABSTRACT: This study aimed to clarify whether electrophysiological and anatomical properties of the slow pathway (SP) could be different between the fast-slow form (F/S) and the slow-slow form (S/S) atrioventricular nodal reentrant tachycardia (AVNRT).METHODS AND RESULTS: Nine patients with F/S and 15 patients with S/S of atypical AVNRT were studied. The patients with S/S were divided into two groups; those with the anterograde SP being eliminated (S/S aSP-E) or preserved (S/S aSP-P) during catheter ablation. HA (CS-His) was determined as the difference of the shortest HA interval between the His bundle region and the coronary sinus (CS) region. The ratio of the amplitudes of atrial and ventricular potential (A/V ratio) of the successful ablation site of the SP was also evaluated. Effective refractory period of the retrograde SP was shorter and HA intervals during both tachycardia and ventricular pacing were longer in F/S than in S/S. HA (CS-His) did not differ between F/S and S/S (-4.3 ± 20.2 vs.-4.4 ± 18.4 ms, NS). The A/V ratio was significantly greater in the S/S aSP-P group compared with the both groups of F/S and S/S aSP-E (0.83 ± 0.29 vs. 0.38 ± 0.09 and 0.26 ± 0.15 ms, P < 0.01).CONCLUSION: Properties of the retrograde SP differ between F/S and S/S of AVNRT. Fast-slow form may utilize the same pathway for the retrograde conduction as the anterograde SP in S/S.
    Europace 08/2013; · 2.77 Impact Factor
  • Akira Fujiki, Masao Sakabe, Ryozo Yoshioka
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    ABSTRACT: Objective Nighttime onset of atrial fibrillation (AF) is sometimes associated with obstructive sleep apnea accompanied by a characteristic heart rate (HR) pattern known as cyclical variation of HR. The aim of this study was to evaluate whether cyclical variation of HR is prevalent in patients with nocturnal AF. Methods The subjects consisted of 34 patients (68±12 years) with paroxysmal AF, including 14 patients with daytime AF and 20 patients with nighttime AF. Holter electrocardiogram (ECGs) were examined for the presence of cyclical variation in HR and to quantify the HR variability within the 40-minute period preceding each AF episode using a fast Fourier transform (FFT) methods. Results Cyclical variation in HR was observed in 12 of 20 (60%) nighttime episodes and in only two of 14 (14%) daytime episodes. The prevalence of cyclical variation in HR was significantly greater in the nighttime AF episodes than in the daytime AF episodes (Chi=5.34, p<0.05). The mean frequency of cyclical variation in HR was 0.015±0.003 Hz. The mean power of the VLF (very low frequency) component (0.008-0.04 Hz) before the onset of AF was significantly greater in the nighttime AF episodes than in the daytime AF episodes. Among the nighttime AF episodes, the power of the HF (high frequency), LF (low frequency) and very low frequency (VLF) components increased significantly just before the onset of AF compared with that observed 40 minutes before onset. Conclusion The high prevalence of cyclical variation in HR observed before nocturnal AF episodes suggests that sleep apnea may play a role in the onset of nighttime AF.
    Internal Medicine 01/2013; 52(19):2169-2172. · 0.97 Impact Factor
  • Masao Sakabe, Ryozo Yoshioka, Akira Fujiki
    Journal of Cardiology Cases 01/2013; 8(6):173–175.
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    ABSTRACT: OBJECTIVES: This study sought to assess the effects of tranilast on atrial remodeling in a canine atrial fibrillation (AF) model. BACKGROUND: Tranilast inhibits transforming growth factor (TGF)-β1 and prevents fibrosis in many pathophysiological settings. However, the effects of tranilast on atrial remodeling remain unclear. METHODS: Beagles were subjected to atrial tachypacing (400 beats/min) for 4 weeks while treated with placebo (control dogs, n = 8) or tranilast (tranilast dogs, n = 10). Sham dogs (n = 6) did not receive atrial tachypacing. Atrioventricular conduction was preserved. Ventricular dysfunction developed in the control and tranilast dogs due to rapid ventricular responses. RESULTS: Atrial fibrillation duration (211 ± 57 s) increased, and AF cycle length and atrial effective refractory period shortened in controls, but these changes were suppressed in tranilast dogs (AF duration, 18 ± 10 s, p < 0.01 vs. control). The L-type calcium channel α1c (Cav1.2) micro ribonucleic acid expression decreased in control dogs (sham 1.38 ± 0.24 vs. control 0.65 ± 0.12, p < 0.01), but not in tranilast dogs (0.97 ± 0.14, p = not significant vs. sham). Prominent atrial fibrosis (fibrous tissue area, sham 0.8 ± 0.1 vs. control 9.3 ± 1.3%, p < 0.01) and increased expression of tissue inhibitor of metalloproteinase protein 1 were observed in control dogs but not in tranilast dogs (fibrous tissue area, 1.4 ± 0.2%, p < 0.01 vs. control). The TGF-β1 (sham 1.00 ± 0.07 vs. control 3.06 ± 0.87, p < 0.05) and Rac1 proteins were overexpressed in control dogs, but their overexpression was inhibited in tranilast dogs (TGF-β1, 1.28 ± 0.20, p < 0.05 vs. control). CONCLUSIONS: Tranilast prevented atrial remodeling and suppressed AF development in a canine model. Its inhibition of TGF-β1 and Rac1 overexpression may contribute to its antiremodeling effects.
    Journal of the American College of Cardiology 12/2012; · 14.09 Impact Factor
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    ABSTRACT: Allopurinol and Atrial Fibrillation. Aims: Oxidative stress could be a possible mechanism and a therapeutic target of atrial fibrillation (AF). Xanthine oxidase (XO) inhibition reduces oxidative stress, but the effects of XO inhibitor on AF have not been evaluated. Hence, we assessed the effects of XO inhibitor, allopurinol, on progression of atrial vulnerability in dogs associated with tachycardia-induced cardiomyopathy. Methods and Results: The dogs were subjected to atrial tachypacing (ATP, 400 bpm) without atrioventricular block for 4 weeks. The dynamics of atrial-tachycardia remodeling were evaluated in allopurinol-treated dogs (ALO, n = 5), placebo-treated controls (CTL, n = 6), and sham-operated dogs (n = 6). In CTL dogs, 4 weeks of ATP significantly increased AF duration (DAF; from 0.2 ± 0.2 seconds to 173 ± 67 seconds, P < 0.05) and decreased atrial effective refractory period (ERP; from 152 ± 9 milliseconds to 80 ± 4 milliseconds at a cycle length of 350 milliseconds, P < 0.01). Allopurinol attenuated the ATP effects on ERP (118 ± 6 milliseconds, P < 0.01) or DAF (0.6 ± 0.3 seconds, P < 0.05). In CTL dogs, ATP-induced rapid ventricular responses decreased left ventricular ejection fraction (LVEF; from 58.6 ± 0.1 to 23.5 ± 2.4%, P < 0.01), and increased left atrial diameter (LAD; from 17 ± 1 mm to 24 ± 1 mm, P < 0.01). ATP increased atrial fibrosis when compared with sham-operated dogs (CTL 10.7 ± 0.8% vs Sham 1.1 ± 0.3%, P < 0.01). Allopurinol suppressed atrial fibrosis (2.3 ± 0.6%, P < 0.01 vs CTL) and eNOS reduction without affecting LVEF (20.6 ± 2.2%, ns) and LAD (23 ± 1 mm, ns). Conclusion: Allopurinol suppresses AF promotion by preventing both electrical and structural remodeling. These results suggest that XO may play an important role in enhancement of atrial vulnerability, and might be a novel target of AF therapy. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1130-1135, October 2012).
    Journal of Cardiovascular Electrophysiology 04/2012; 23(10):1130-5. · 3.48 Impact Factor
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    ABSTRACT: Anticoagulation control quality affects the incidence of thromboembolic events in atrial fibrillation (AF) patients. However, the effects of anticoagulation control quality on the prothrombotic state of AF patients are unclear. Ninety-five AF patients who had been treated with warfarin were prospectively followed-up for 449 ± 92 days. We analyzed whether time in the therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time, percentage of INR values in the range (%INR), and coefficient of variation of INR values (CV-INR) were related to D-dimer levels. The mean values of TTR, %INR, and CV-INR were 62%, 59%, and 0.19, respectively, and their median values were 67%, 63%, and 0.19, respectively. TTR was significantly correlated with %INR (R(2) = 0.917, P<0.01), but not with CV-INR (R(2) = 0.050, P = 0.26). The mean and median D-dimer levels were 0.79 and 0.60 µg/ml, respectively. Low TTR, low %INR, and high CV-INR were found to contribute to high D-dimer levels (P = 0.02, 0.03, and 0.02, respectively). In AF patients treated with warfarin, not only the duration outside the target INR range, but also the fluctuation in INR level may influence the prothrombotic state.
    Circulation Journal 12/2011; 76(2):317-21. · 3.58 Impact Factor
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    ABSTRACT: Idiopathic ventricular fibrillation (IVF) with early repolarization (ER) has recently been reported; however, ER is a common finding in healthy subjects and is also found sporadically in patients with Wolff-Parkinson-White (WPW) syndrome. The present study was designed to evaluate the prevalence and clinical significance of ER in patients with WPW syndrome. One hundred and eleven patients with WPW syndrome were studied retrospectively. Early repolarization was defined as QRS slurring or notching with J-point elevation ≥ 1 mm. The prevalence of ER was determined before and after successful catheter ablation. Before ablation, ER was found in 35 of 75 patients with a left free wall, 6 of 23 with a right free wall, and 7 of 13 with a septal accessory pathway (48 of 111, 43% as a whole). Early repolarization was always observed in leads with positive deflection of the initial part of the delta wave. After successful ablation of accessory pathways, ER was preserved in 28 (25%), disappeared in 20 (18%), and newly developed in 8 (7%) patients. In the remaining 55 (50%) patients, ER was not observed either before or after ablation. In patients with persistent ER, the amplitude and width of ER were significantly decreased 3-7 days after the ablation (1.7 ± 0.7 vs. 1.4 ± 0.6 mm, P < 0.005 and 42 ± 11 vs. 34 ± 9 ms, P < 0.001, respectively). In patients with WPW syndrome, ER could be partly related to early depolarization through the accessory pathway. However, persistent ER and new ER appearing after the ablation were frequently found. Therefore, in these patients, mechanisms other than early depolarization may be involved in the genesis of ER.
    Europace 05/2011; 13(8):1195-200. · 2.77 Impact Factor
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    ABSTRACT: During atrial fibrillation (AF) irregularity of RR intervals may modify QT/RR relation differently from sinus rhythm. The purpose of this study was to compare QT/RR relation based on a single-beat analysis using the first preceding RR interval with the modified RR interval reflecting not only the first preceding but also the second and further preceding RR intervals during AF. QT and RR intervals were measured using an automatic QT analyzing system in 32 patients who had both AF and sinus rhythm on the same 24-h Holter ECG recording. In 12 patients antiarrhythmic drugs (AADs) were administered. To reflect irregularity of the preceding RR intervals during AF, a modified RR (mRR) using a weighted average of five successive RR intervals: (5RR(1)+2RR(2)+RR(3)+RR(4)+RR(5))/10 was adopted. Linear regression analyses between QT and RR intervals were performed using the preceding RR(1) (QT/RR) and the modified RR (QT/mRR) during AF. During AF the slope of QT/RR was lower than that of QT/mRR and was also lower than that of QT/RR during sinus rhythm in patients with and without AAD. Slopes of regression line in QT/RR during sinus rhythm, QT/RR and QT/mRR during AF were steeper in patients with AAD than those in patients without. Slopes of QT/RR during sinus rhythm correlated with those of QT/mRR (r=0.79, p<0.01) better than those of QT/RR (r=0.64, p<0.05) during AF. QT interval at an RR interval of 1.20s or 1.00 s obtained from QT/RR during AF was significantly smaller than that during sinus rhythm in patients with and without AAD. The slope of QT/mRR during AF became closer to that of QT/RR during sinus rhythm compared with that of QT/RR during AF. QT interval during sinus rhythm could be estimated better using QT/mRR than using QT/RR during AF.
    Journal of Cardiology 03/2011; 57(3):269-74. · 2.30 Impact Factor
  • Akira Fujiki, Masao Sakabe
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    ABSTRACT: The aim of this study was to compare QT/RR relation based on a 15-s averaged beat ECG with a single beat ECG during atrial fibrillation (AF) and to determine which was better to estimate the QT interval after sinus restoration. QT and RR intervals were measured using an automatic QT analyzing system in 33 patients who had both AF and sinus rhythm on the same 24-h Holter ECG recording. In 14 patients, antiarrhythmic drugs (AAD) were administered. QT/RR relations were analyzed from ECG waves obtained by the summation of consecutive QRS-T complexes during each 15-s period (QT/RR-average) and a single beat QRS-T (QT/RR-single). During sinus rhythm, the slope of QT/RR-average did not differ from that of QT/RR-single in patients with and without AAD. On the other hand, during AF, the slope of QT/RR-average was significantly greater than that of QT/RR-single (without AAD: 0.12±0.06 vs. 0.06±0.03, P<0.001; with AAD: 0.15±0.05 vs. 0.08±0.04, P<0.001). During AF, the QT interval at an RR interval of 1.2-s (QT-1.2) determined from QT/RR-average was significantly greater than QT-1.2 from QT/RR-single in patients with and without AAD. QT-1.2 in QT/RR-single during AF was significantly smaller than that during sinus rhythm but QT-1.2 in QT/RR-average during AF was not. The QT interval after sinus restoration could be estimated better using QT/RR-average than using QT/RR-single during AF.
    Circulation Journal 02/2011; 75(2):274-9. · 3.58 Impact Factor
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    Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2011; 57(14).
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    ABSTRACT: An 86-year-old woman was admitted to the hospital for syncope and convulsion 4 days after starting antibiotic therapy for pneumonia with oral garenoxacin 400 mg/day. She had a VDD pacemaker for complete atrioventricular (AV) block. Her electrocardiogram showed marked QT prolongation and during pacemaker interrogation pacing failure probably due to battery depletion induced torsades de pointes. After cessation of garenoxacin, QTc returned to normal range subsequently and a new pacemaker was implanted. In patients with risks of QT prolongation, garenoxacin should be used cautiously with QT interval monitoring.
    Journal of Cardiology Cases 01/2011; 3(2).
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    ABSTRACT: Pulmonary vein (PV)-encircling ablation, which is effective in suppressing atrial fibrillation (AF), damages autonomic ganglia near the PV ostia. This study examined the effects of PV isolation (PVI) vs. peri-PV ganglionic plexus ablation (GPA) in two discrete canine AF models: ventricular tachypacing (240 bpm, 2 weeks)-induced congestive heart failure (CHF), and atrial tachypacing (400 bpm, 1 week)-induced atrial tachycardia remodeling (ATR). All PVs were isolated with an epicardial radiofrequency clamp in nine CHF and eight ATR dogs. Peri-PV ganglionic plexi (identified by bradycardic responses to high-frequency stimulation) were ablated in six CHF and five ATR dogs with an epicardial radiofrequency-ablation pen. Electrophysiologic measurements, including 240-electrode AF mapping, were obtained and dominant frequencies (DFs) determined. Atrial growth associated protein-43 (GAP-43) and neurofilament-M (NF-M) expression were determined immunohistologically. In CHF, neither PVI nor GPA affected AF duration, DF or the already low AF vulnerability. In ATR, PVI reduced AF vulnerability (75 ± 6% to 55 ± 11%, P< 0.05) but did not alter AF duration or DF. In contrast, GPA prolonged atrial refractory period and decreased AF vulnerability (75 ± 8 to 30 ± 10%, P< 0.05), AF duration (617 ± 246 to 39 ± 23 s, **P< 0.01), and DF (11.4 ± 0.6 to 8.6 ± 0.3** Hz, left atrium) in ATR dogs. Both GAP-43 and NF-M expression were decreased in CHF (by 63.1** and 60.0%**) and increased in ATR (by 65.5** and 92.1%, P< 0.001) compared with control. PVs play a minor role in experimental AF due to CHF or ATR, but autonomic ganglia are important in AF related to ATR. Differential neural remodelling may contribute to varying effects of GPA in discrete AF substrates.
    Cardiovascular research 10/2010; 89(4):825-33. · 5.81 Impact Factor
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    ABSTRACT: A 54-year-old man with prior inferior myocardial infarction suffered from monomorphic ventricular tachycardia (VT) with narrow QRS complex of 120 ms. During VT, a fragmented prepotential preceding QRS onset by 30 ms at the right ventricular posterior septum and a late diastolic potential preceding QRS onset by 70 ms at the infarcted posterior mitral annulus were recorded. Radiofrequency energy delivered to the late diastolic potential at the posterior mitral annulus eliminated VT. During sinus rhythm, the late diastolic potential shifted to the end of QRS complex and no Purkinje potentials were observed. Synchronized excitation of both ventricles from the posterior infarcted mitral annulus in this patient may make the QRS width during VT narrow, without involvement of the His-Purkinje system.
    Heart and Vessels 03/2010; 25(2):170-3. · 2.13 Impact Factor
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    ABSTRACT: There are many similarities between atrial effects of atrial tachycardia remodeling (ATR) and vagal nerve stimulation (VS): both promote atrial fibrillation (AF), reduce atrial effective refractory period (AERP) and AERP rate accommodation, enhance AERP heterogeneity, and increase inward-rectifier K+ current. This study sought to compare the consequences of ATR and VS at similar levels of AERP abbreviation in dogs. ATR dogs (n = 6) were subjected to 7-day atrial tachypacing at 400 beats/min, with radiofrequency-induced atrioventricular block and ventricular demand pacing (80 beats/min) to control ventricular response. VS was applied in 6 matched dogs with stimulation parameters selected to produce similar mean AERP values to ATR dogs. ATR and VS produced similarly short AERPs (79 +/- 12 and 80 +/- 12 ms, respectively), AERP rate-adaptation loss, and AERP heterogeneity increases. Although both ATR and VS increased AF duration, VS was significantly more effective in AF promotion, with mean AF duration of 992 +/- 134 seconds, versus 440 +/- 240 seconds (P <.05) under ATR. The greater AF-promoting effect of VS was associated with greater mean dominant frequency values during AF (11.7 +/- 1.8 versus 10.0 +/- 1.3 Hz ATR, P <.05). VS greatly enhanced the spatial dominant frequency variability, increasing the coefficient of variation to 15.2 +/- 1.9 Hz, versus 8.9 +/- 1.5 Hz for ATR (P <.05), primarily by increasing the per-dog maximum dominant frequency (15.4 +/- 0.6 Hz versus 12.5 +/- 0.6 for ATR, P <.01). For matched AERP values, VS promotes AF more strongly than ATR. Despite similar AERP changes, VS produces considerably greater increases in dominant frequencies, particularly maximum values, consistent with previous suggestions that inward-rectifier K+ current enhancement is particularly effective at accelerating and stabilizing spiral wave rotors that maintain AF.
    Heart rhythm: the official journal of the Heart Rhythm Society 10/2009; 6(10):1465-72. · 4.56 Impact Factor
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    ABSTRACT: This study evaluated antiarrhythmic effects of d,l-sotalol in a canine atrial fibrillation (AF) model with left ventricular dysfunction. Thirteen beagles (Sotalol group n=7 and Control group n=6) were subjected to atrial tachypacing (ATP) (400 beats/min) with intact atrioventricular conduction for 4 weeks. Oral d,l-sotalol (2 mg/kg) was administered 1 week after starting ATP and continued throughout the experiment. One week after starting ATP, atrial effective refractory periods (AERPs) were shortened in both groups. However, d,l-sotalol treatment gradually prolonged AERP, resulting in a significant prolongation of AERP compared with the Control group at 4 weeks (Control 76 +/-4 and Sotalol 126 +/-5 ms, p<0.01). d,l-Sotalol treatment showed lower AF inducibility and shorter AF duration at 4 weeks. In the control group, expressions of L-type Ca(2+) channel alpha1c and Kv4.3 mRNA were downregulated by 46.2% and 43.0%, respectively, after 4 weeks of ATP; d,l-sotalol treatment did not affect these changes. d,l-Sotalol treatment prolonged AERP, even after atrial electrical remodeling had developed, and prevented AF perpetuation without affecting downregulated expression of L-type Ca(2+) channel alpha1c and Kv4.3 mRNA in an ATP-induced canine AF model.
    Circulation Journal 09/2009; 73(10):1820-8. · 3.58 Impact Factor
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    ABSTRACT: Sinoatrial node (SAN) dysfunction is frequently associated with atrial tachyarrhythmias (ATs). Abnormalities in SAN pacemaker function after termination of ATs can cause syncope and require pacemaker implantation, but underlying mechanisms remain poorly understood. This study examined the hypothesis that ATs impair SAN function by altering ion channel expression. SAN tissues were obtained from 28 control dogs and 31 dogs with 7-day atrial tachypacing (400 bpm). Ionic currents were measured from single SAN cells with whole-cell patch-clamp techniques. Atrial tachypacing increased SAN recovery time in vivo by approximately 70% (P<0.01), a change which reflects impaired SAN function. In dogs that underwent atrial tachypacing, SAN mRNA expression (real-time reverse-transcription polymerase chain reaction) was reduced for hyperpolarization-activated cyclic nucleotide-gated subunits (HCN2 and HCN4) by >50% (P<0.01) and for the beta-subunit minK by approximately 42% (P<0.05). SAN transcript expression for the rapid delayed-rectifier (I(Kr)) alpha-subunit ERG, the slow delayed-rectifier (I(Ks)) alpha-subunit KvLQT1, the beta-subunit MiRP1, the L-type (I(CaL)) and T-type (I(CaT)) Ca2+-current subunits Cav1.2 and Cav3.1, and the gap-junction subunit connexin 43 (were unaffected by atrial tachypacing. Atrial tachypacing reduced densities of the HCN-related funny current (I(f)) and I(Ks) by approximately 48% (P<0.001) and approximately 34% (P<0.01), respectively, with no change in voltage dependence or kinetics. I(Kr), I(CaL), and I(CaT) were unaffected. SAN cells lacked Ba2+-sensitive inward-rectifier currents, irrespective of AT. SAN action potential simulations that incorporated AT-induced alterations in I(f) accounted for slowing of periodicity, with no additional contribution from changes in I(Ks). AT downregulates SAN HCN2/4 and minK subunit expression, along with the corresponding currents I(f) and I(Ks). Tachycardia-induced remodeling of SAN ion channel expression, particularly for the "pacemaker" subunit I(f), may contribute to the clinically significant association between SAN dysfunction and supraventricular tachyarrhythmias.
    Circulation 04/2009; 119(12):1576-85. · 15.20 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is a problem of growing proportions. Recent studies have increased interest in fast-unbinding Na(+) channel blockers like vernakalant (RSD1235) and ranolazine for AF therapy, but the mechanism of efficacy is poorly understood. To study how fast-unbinding I(Na) blockers affect AF, we developed realistic mathematical models of state-dependent Na(+) channel block, using a lidocaine model as a prototype, and studied the effects on simulated cholinergic AF in two- and three-dimensional atrial substrates. We then compared the results with in vivo effects of lidocaine on vagotonic AF in dogs. Lidocaine action was modeled with the Hondeghem-Katzung modulated-receptor theory and maximum affinity for activated Na(+) channels. Lidocaine produced frequency-dependent Na(+) channel blocking and conduction slowing effects and terminated AF in both two- and three-dimensional models with concentration-dependent efficacy (maximum approximately 89% at 60 microM). AF termination was not related to increases in wavelength, which tended to decrease with the drug, but rather to decreased source Na(+) current in the face of large ACh-sensitive K(+) current-related sinks, leading to the destabilization of primary generator rotors and a great reduction in wavebreak, which caused primary rotor annihilations in the absence of secondary rotors to resume generator activity. Lidocaine also reduced the variability and maximum values of the dominant frequency distribution during AF. Qualitatively similar results were obtained in vivo for lidocaine effects on vagal AF in dogs, with an efficacy of 86% at 2 mg/kg iv, as well as with simulations using the guarded-receptor model of lidocaine action. These results provide new insights into the mechanisms by which rapidly unbinding class I antiarrhythmic agents, a class including several novel compounds of considerable promise, terminate AF.
    AJP Heart and Circulatory Physiology 09/2008; 295(4):H1489-504. · 4.01 Impact Factor
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    ABSTRACT: We assessed responses to slow pathway ablation with respect to the appearance of ventriculoatrial (VA) block during junctional rhythm in both typical and atypical types of atrioventricular nodal re-entrant tachycardia (AVNRT). The 31 subjects included 16 patients with slow-fast type of typical AVNRT and 15 patients with atypical AVNRT (9 patients with fast-slow type and 6 patients with slow-slow type). During atypical AVNRT, the HA interval was prolonged (>70 ms) and the earliest atrial activation was located around the coronary sinus (CS) ostium. The difference in atrial activation times at the CS ostium and His-bundle area [A(CS-His)] during AVNRT was measured. Slow pathway ablation was performed using a classical electro-anatomical approach. In typical AVNRT, A(CS-His) was -21.3 +/- 3.4 ms, and the HA interval was 34 +/- 14 ms. During slow pathway ablation, all patients with typical AVNRT had junctional rhythm with retrograde atrial conduction. In contrast, in patients with atypical AVNRT, A(CS-His) was 12 +/- 19.3 ms and the HA interval was 189 +/- 77 ms. In 13 of the 15 patients with atypical AVNRT, slow pathway ablation induced junctional rhythm, which was not associated with retrograde atrial conduction. After ablation, AVNRT became non-inducible and antegrade atrioventricular (AV) conduction was preserved in all patients. In patients with atypical AVNRT, junctional rhythm with VA block during slow pathway ablation is commonly observed and indicates the success of the ablation of retrograde slow pathway conduction, but has no relation to the risk of subsequent AV block. During junctional rhythm, occasional appearance of the sinus beats with intact antegrade AV conduction is essential for safety of ablation.
    Europace 06/2008; 10(8):982-7. · 2.77 Impact Factor
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    ABSTRACT: Heat shock proteins (HSPs) are a set of endogenous cytoprotective factors activated by various pathological conditions. This study addressed the effects of geranylgeranylacetone (GGA), an orally active HSP inducer, on the atrial fibrillation (AF) substrate associated with acute atrial ischaemia (AI). Four groups of mongrel dogs were studied: (1) a group subjected to AI without GGA (AI-CTL, n = 13 dogs); (2) dogs that underwent AI after GGA pretreatment (120 mg/kg/day; AI-GGA, n = 12); (3) dogs receiving GGA pretreatment without AI (n = 5); (4) control dogs for tissue sampling (n = 5). Isolated right AI was produced by occluding a right atrial (RA) coronary-artery branch. AI reduced ischaemic-zone conduction velocity (CV, from 94 +/- 3 to 46 +/- 5 cm/s; P < 0.01) and increased maximum local phase delays (P95, from 1.6 +/- 0.1 to 4.6 +/- 0.6 ms/mm; P < 0.01), conduction heterogeneity index (CHI, from 0.7 +/- 0.1 to 2.9 +/- 0.5; P < 0.01), and the mean duration of burst pacing-induced AF (DAF, from 44 +/- 18 to 890 +/- 323 s; P < 0.01) in AI-CTL dogs. GGA pretreatment attenuated ischaemia-induced conduction abnormalities (CV, 77 +/- 8 cm/s; P95, 2.1 +/- 0.4 ms/mm; CHI, 1.1 +/- 0.2; all P < 0.01 vs. AI-CTL) and DAF (328 +/- 249 s; P < 0.01) in AI-GGA dogs. GGA treatment alone, without ischaemia, did not alter DAF or conduction indices. AI slightly prolonged atrial refractory period, an effect also prevented by GGA. GGA significantly increased HSP70 protein expression in RA tissues of ischaemic hearts. GGA prevents ischaemia-induced atrial conduction abnormalities and suppresses ischaemia-related AF. These results suggest that HSP induction might be a useful new anti-AF intervention for patients with coronary artery disease.
    Cardiovascular Research 05/2008; 78(1):63-70. · 5.81 Impact Factor

Publication Stats

643 Citations
208.70 Total Impact Points

Institutions

  • 2006–2013
    • University of Toyama
      • • Department of Internal Medicine 1
      • • Faculty of Medicine
      Тояма, Toyama, Japan
  • 2011–2012
    • Japan Red Cross Fukuoka Hospital
      Hukuoka, Fukuoka, Japan
  • 2007–2010
    • Montreal Heart Institute
      • Department of Medicine
      Montréal, Quebec, Canada
  • 2002–2005
    • Toyama Medical and Pharmaceutical University
      Тояма, Toyama, Japan