Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model.

Background Recent clinical trials have demonstrated the possible pleiotropic effects of SGLT2 (sodium-glucose cotransporter 2) inhibitors in clinical cardiovascular diseases. Atrial electrical and structural remodeling is important as an atrial fibrillation (AF) substrate. Methods and Results The present study assessed the effect of canagliflozin (CAN), an SGLT2 inhibitor, on atrial remodeling in a canine AF model.

Liraglutide suppresses atrial electrophysiological changes.

We have shown that a dipeptidyl peptidase 4 (DPP-4) inhibitor suppresses atrial remodeling in a canine atrial fibrillation (AF) model. Glucagon-like peptide-1 (GLP-1) is increased by DPP-4 inhibitors. However, it is not clear whether GLP-1 is involved in the suppression of atrial remodeling.

Linagliptin Suppresses Electrical and Structural Remodeling in the Isoproterenol Induced Myocardial Injury Model.

The effect of DPP-4 inhibitor on the electrical and structural remodeling in myocardial injury has not been evaluated. We hypothesized that linagliptin, DPP-4 inhibitor, suppresses myocardial remodeling in the isoproterenol (ISP)-induced myocardial injury model.Sprague-Dawley rats were assigned to 3 groups: 1) sham group, 2) ISP group (subcutaneous ISP injection of 70 mg/kg), and 3) ISP + linagliptin (ISP + Lin) (5 mg/kg/day, p.

Antiremodeling Effect of Xanthine Oxidase Inhibition in a Canine Model of Atrial Fibrillation.

In a canine rapid atrial stimulation model of atrial fibrillation (AF), we have demonstrated an increased production of reactive oxygen species (ROS) along with electrical and structural remodeling. In the present study, we hypothesized that antioxidants can suppress atrial remodeling canines with AF. We therefore evaluated the effect of febuxostat, a xanthine oxidase (XO) inhibitor and a pure antioxidant, on atrial remodeling.

Linagliptin prevents atrial electrical and structural remodeling in a canine model of atrial fibrillation.

Dipeptidyl peptidase 4 (DPP-4) inhibitors have recently been reported to exhibit additional cardioprotective effects; however, their effect in atrial remodeling, such as in atrial fibrillation (AF), remains unclear. In this study, the effect of linagliptin on atrial electrical and structural remodeling was evaluated in a canine AF model. Sixteen beagle dogs with 3-week atrial rapid stimulation were divided into the linagliptin group (9 mg/kg/day, n = 8) and pacing control group (n = 8).

The J-wave as a Predictor of Life-Threatening Arrhythmia in ICD Patients.

The J-wave has been reported to be associated with life-threatening ventricular arrhythmia. However, the clinical implication of the J-wave is still unclear in patients with an implantable cardioverter defibrillator (ICD).The study population consisted of 170 ICD patients (age, 56 ± 16 years, 79.

Discrimination of Paroxysmal and Persistent Atrial Fibrillation in Patients With New-Onset Atrial Fibrillation.

Discrimination between paroxysmal and persistent atrial fibrillation (PAF and persistent AF) is important for determining the therapeutic strategy in patients with new-onset AF. We evaluated various clinical factors and P wave morphology to discriminate PAF and persistent AF patients in patients with new-onset AF.The study population consisted of 79 patients with new-onset AF (70.

Aliskiren suppresses atrial electrical and structural remodeling in a canine model of atrial fibrillation.

Aliskiren, a direct renin inhibitor is expected to achieve sufficient suppression of renin-angiotensin system. We evaluated the effect of aliskiren on the electrical and structural remodeling in a canine atrial fibrillation (AF) model. Twenty-eight dogs were divided into three groups: (1) pacing control group (n = 12), with continuous atrial rapid pacing for 3 or 6 weeks, (2) pacing + aliskiren group (n = 12), with oral aliskiren (30 mg/kg/day), and (3) sham group (n = 4), no pacing nor drug administration.

Polytherapy with sodium channel-blocking antiepileptic drugs is associated with arrhythmogenic ST-T abnormality in patients with epilepsy.

Purpose: Recent reports have documented the appearance of Brugada-type ST elevation in cases of overdose of antiepileptic drugs (AEDs). However, little is known about changes on electrocardiographs (ECGs) during AED use at therapeutic doses. AEDs may cause Brugada-type ST elevation or J-wave-like intraventricular conduction delays through an ion channel-blocking effect.

Efficacy and Limitations of Tachycardia Detection Interval Guided Reprogramming for Reduction of Inappropriate Shock in Implantable Cardioverter-Defibrillator Patients.

The avoidance of inappropriate shock therapy is an important clinical issue in implantable cardioverter-defibrillator (ICD) patients. We retrospectively analyzed therapeutic events in ICD patients, and the effect of tachycardia detection interval (TDI) and tachycardia cycle length (TCL) guided reprograming on the reduction of inappropriate ICD therapy. The clinical determinants of after reprogramming were also evaluated.

Rivaroxaban Inhibits Angiotensin II-Induced Activation in Cultured Mouse Cardiac Fibroblasts Through the Modulation of NF-κB Pathway.

Cell migration, proliferation, and differentiation of cardiac fibroblasts (CFs) play a central role in cardiac fibrosis. Factor Xa (FXa)-dependent protease-activated receptor (PAR)-1 and PAR-2 have been reported as important targets in proinflammatory and fibroproliferative diseases. From this viewpoint, we aimed to investigate whether treatment of rivaroxaban, an approved oral direct FXa inhibitor, attenuates functional changes in angiotensin (Ang) II-induced mouse CFs.

Prediction of new onset atrial fibrillation through P wave analysis in 12 lead ECG.

It is unknown whether 12-lead ECG can predict new-onset AF. In the present study, we identified patients with new onset AF from our digitally stored ECG database, and the P wave morphologies were analyzed in their preceding sinus rhythm recordings as the precursor state for AF. The P wave was analyzed in the most recent ECG recording of sinus rhythm preceding new onset AF within 12 months.

Cardiomyocyte-derived mitochondrial superoxide causes myocardial electrical remodeling by downregulating potassium channels and related molecules.

Background: This study was designed to investigate the role of a primary hyperoxidative stress in myocardial electrical remodeling using heterozygous heart/muscle-specific manganese superoxide dismutase-deficient (H/M-Sod2(+/-)) mice treated with L-buthionine-sulfoximine (BSO).

Methods And Results: Both H/M-Sod2(+/-)and wild-type (WT) mice were treated with intra-peritoneal BSO or saline for 7 days, and divided into 4 groups: H/M-Sod2(+/-)+BSO, WT+BSO, H/M-Sod2(+/-)control, and WT control. The ventricular effective refractory period (ERP) and the monophasic action potential duration (MAPD) were determined.

Effect of carvedilol on atrial remodeling in canine model of atrial fibrillation.

Aims: We evaluated the effect of carvedilol, a beta-blocker with anti-oxidative action, against the atrial fibrillation (AF) inducibility, the development of atrial remodeling and the oxidative stress markers in a canine AF model.

Methods And Results: AF model was produced by performing 6-week rapid atrial stimulation in 15 dogs. The animals were divided into the following three groups: (I) pacing + carvedilol group (n=5); (II) pacing control group (n=5); and (III) non-pacing group (n=5).

Prophylactic statin administration may prevent shortening of the fibrillation cycle length in patients with new-onset atrial fibrillation.

Patients with recently diagnosed atrial fibrillation (AF) tend to exhibit a longer fibrillation cycle length (FCL) than those having a longer clinical history. However, the electrophysiological properties of new-onset AF may vary because of the clinical background of patients. In this study, we evaluated clinical factors to identify the determinants of FCL in new-onset AF.

Prediction of inappropriate implantable cardioverter-defibrillator therapies through parameters obtained in a simple exercise stress test.

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).

Cardioprotective effects of sarcolemmal and mitochondrial K-ATP channel openers in an experimental model of autoimmune myocarditis. Role of the reduction in calcium overload during acute heart failure.

It has been reported that K-ATP channel openers have a cardioprotective effect in acute ischemia as a pharmacological preconditioning effect. In the present study, the chronic effects of clinical K-ATP channel openers, ie, nicorandil (Nic) and mexiletine (Mex), on cardiac function were evaluated in a rat model of experimental autoimmune myocarditis (EAM). Nicorandil (3 or 10 mg/kg/day) or Mex (10 or 25 mg/kg/day) was administered to the EAM rats, and the effects were compared with those in untreated EAM rats (control EAM) and sham rats without EAM on day 21 (acute phase) or day 60 (chronic phase).

Angiotensin II-mediated up-regulation of connective tissue growth factor promotes atrial tissue fibrosis in the canine atrial fibrillation model.

Aims: 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.

Methods And Results: Fifteen canine AF models were produced by rapid atrial stimulation.

Evaluation of the impact of atrial fibrillation on rehospitalization events in heart failure patients in recent years.

Background: 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.

Methods And Results: 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.

Repetitive evaluation of fibrillation cycle length predicts the efficacy of bepridil for interruption of long-lasting persistent atrial fibrillation.

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.

Progression of ventricular remodeling and arrhythmia in the primary hyperoxidative state of glutathione-depleted rats.

Background: 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.

Methods And Results: Sprague-Dawley rats were treated with L-buthionine-sulfoximine (BSO, 30 mmol · L(-1) · day(-1)) for 14 days.

Combined effects of up- and downstream therapies on atrial fibrillation in a canine rapid stimulation model.

Background: Recent reports suggest angiotensin receptor blockers (ARBs) and some antiarrhythmic agents affect atrial remodeling in atrial fibrillation (AF). We evaluated the effect of combination therapy with olmesartan (Olm) and bepridil (Bep) in a canine model of AF.

Methods And Results: An atrial stimulation device was implanted in 10 dogs undergoing 6-week pacing at 400 bpm.

N-acetylcysteine suppresses the progression of ventricular remodeling in acute myocarditis: studies in an experimental autoimmune myocarditis (EAM) model.

Background: Electrical and structural remodeling, characterized by prolonged action potential duration (APD), Kv4.2 downregulation and cellular infiltration were studied in rat experimental autoimmune myocarditis (EAM). Because the reactive oxygen species (ROS) has been speculated to play a role in the promotion of such remodeling, the effect of N-acetylcysteine (NAC) on the progression of ventricular remodeling was evaluated.

Risks and benefits of combined use of bucolome and warfarin in anticoagulation therapy.

Although bucolome has been used empirically to enhance and stabilize warfarin action in some institutes, the clinical risks and benefits of this combination are unclear. In the present study, warfarin monotherapy (WM) and bucolome combination (BC) therapy were compared in anticoagulation therapy.One hundred and ninety-five patients indicated for anticoagulation therapy were randomly assigned to WM (n = 98) or BC (bucolome 300 mg/day, n = 97).