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Background Rikkunshito (RKT), a traditional herbal medicine, has been demonstrated to exert anti-inflammatory, anti-apoptotic, and anti-fibrotic effects in several organs. This study tested the hypothesis that RKT can suppress angiotensin II (AngII)-induced inflammatory atrial fibrosis and ameliorate enhanced vulnerability to atrial fibrillation (AF). Methods Eight-week-old male C57BL/6 mice were subcutaneously infused with either vehicle or AngII (2.0 mg/kg/day) for 2 weeks. Water or RKT at a dose of 1000 mg/kg/day were orally administered once daily for 2 weeks. Morphological, histological, and biochemical analyses were performed. AF was induced either by transesophageal burst pacing in vivo or by burst/extrastimuli in isolated perfused hearts using a Langendorff apparatus. Results RKT at a dose of 1000 mg/kg/day for 2 weeks attenuated atrial interstitial fibrosis and profibrotic and proinflammatory signals induced by continuous infusion of AngII. RKT attenuated AngII-induced enhanced vulnerability to AF in in vivo experiments and in isolated perfused hearts. Atractylodin, an active component of RKT, exhibited antifibrotic activity comparable to that of RKT. RKT reversed AngII-induced suppression of sirtuin 1 (Sirt1) translocation to the nuclei. RKT suppressed AngII-induced phosphorylation of IκB, overexpression of p53, and cellular apoptotic signals and apoptosis. All of the antagonizing effects of RKT against AngII were attenuated by a concomitant treatment with a growth hormone secretagogue receptor (GHSR)-inhibitor. Conclusion Our results demonstrated that RKT prevented atrial fibrosis and attenuated enhanced vulnerability to AF induced by AngII. The results also suggested that potentiating the GHSR-Sirt1 pathway is involved in these processes.

Although J-waves have been known to be associated with vulnerability to ventricular fibrillation, their electrophysiologic mechanism remains to be elucidated. The papillary muscles (PMs) of the left ventricle (LV) have been recognized as the target site of radiofrequency ablation for ventricular arrhythmias. However, the relationship between PM hypertrophy and J-waves has not been investigated.To investigate the electrocardiographic characteristics, including the J-waves, in patients with solitary PM hypertrophy.We studied 101 patients with PM hypertrophy without LV hypertrophy (PMH group) and 159 age- and sex-matched control subjects (control group). The parameters of the 12-lead electrocardiogram and the echocardiogram were compared between the two groups.Compared with the control group, the PMH group had significantly higher incidence (15% vs. 33%, p=0.001) and amplitude (0.17±0.06mV vs. 0.28±0.17mV, p0.01) of J-waves; significantly longer QRS, QTc, and JTc intervals (p=0.0001, p0.0001, and p0.05, respectively); significantly greater Sokolow-Lyon index (p0.001); and significantly greater LV wall thickness and LV mass index (p0.0001 for each). Multivariate logistic regression analysis showed that only the PM hypertrophy was an independent predictor of the presence of J-waves.PM hypertrophy was related to the genesis of J-waves.

Background Coagulation factor Xa (FXa) promotes thrombus formation and exacerbates inflammation via activation of protease-activated receptor (PAR)-2. We tested the hypothesis of whether administration of direct oral anticoagulant, rivaroxaban, would attenuate transverse aortic constriction (TAC)-induced atrial inflammatory fibrosis and vulnerability to atrial fibrillation (AF) in mice. Methods Ten-week-old male CL57/B6 mice were divided into a sham-operation (CNT) group and TAC-surgery group. These two groups were then subdivided into vehicle (VEH) and rivaroxaban (RVX) treatment (30 μg/g/day) groups. We assessed PAR-2 expression in response to TAC-related stimulation using rat cultured cells. Results TAC-induced left atrial thrombus formation was not observed in the TAC-RVX group. Cardiac PAR-2 upregulation was observed in both TAC groups. In the quantitative analysis of mRNA levels, cardiac PAR-2 upregulation was attenuated in the TAC-RVX group compared to TAC-VEH group. In histological evaluation, the TAC-VEH group showed cardiac inhomogeneous interstitial fibrosis and abundant infiltration of macrophages, which were attenuated by RVX administration. Electrophysiological examination revealed that AF duration in the TAC group was shortened by RVX administration. TAC-induced protein overexpression of monocyte chemoattractant protein-1, and mRNA overexpression of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in the left atrium was suppressed by RVX treatment. In cardiac fibroblasts, persistent intermittent stretch upregulated PAR-2, which was suppressed by RVX pre-incubation. Conclusions These observations demonstrate that coagulation FXa inhibitor probably has a cardioprotective effect against pressure-overload-induced atrial remodeling.

Background Spleen reserves monocytes, which deploy to inflammatory sites. Monocytosis is known to be observed in chronic low-grade inflammatory state, including chronic heart failure (CHF). CHF also induces splenomegaly. We tested the hypotheses that the number of peripheral blood monocytes and size of spleen at baseline could be related to the response to cardiac resynchronization therapy (CRT). Methods From 2010, a total of 49 consecutive patients implanted with CRT device were evaluated at baseline and 6–8 months later. The size of spleen was evaluated at baseline by computed tomography. Blood monocyte counts (BMCs) were examined by blood test apparatus. Results Patients were categorized as responders (13 female, mean age 69.0 ± 7.9 years, n = 34) and nonresponders (2 female, mean age 72.0 ± 8.8 years, n = 15) according to echocardiographic findings. In non-responders, spleen index was also greater in non-responders than in responders (4504 ± 1338 mm2 vs. 3240 ± 1115 mm2; mean ± SE, p Conclusions Our results demonstrated that BMC and the size of spleen might be important factors for response to CRT.

SummaryBackgroundA number of experimental and clinical studies have demonstrated a cardioprotective effect of statins; however, the effect of atorvastatin on cardiac function in patients with an acute myocardial infarction (AMI) has not been established.Methods and resultsThirty consecutive patients with an AMI (16 males and 14 females) were enrolled. All the patients underwent successful percutaneous coronary intervention in the early phase after the onset of an AMI. Patients with a total cholesterol level >200mg/dL on admission (n=14) were assigned to the atorvastatin group. They began taking 10mg of atorvastatin daily within 48h after the onset of the AMI, while the other patients (n=16) did not receive atorvastatin and served as the control group. Echocardiography and blood sampling to measure brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) levels were repeated on the 2nd day (2D), 3 weeks (3W), 12 weeks (12W), and 24 weeks (24W) after the onset of the AMI. The percentage of patients with a high BNP level (BNP>20pg/mL) was significantly decreased from 2D to 24W in the atorvastatin group, but not in the control group (100 to 57% in the atorvastatin group, p40pg/mL) (62 to 21% in the atorvastatin group, p