[Show abstract][Hide abstract] ABSTRACT: Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene which encodes dystrophin protein. Dystrophin defect affects cardiac muscle as well as skeletal muscle. Cardiac dysfunction is observed in all patients with DMD over 18 years of age, but there is no curative treatment for DMD cardiomyopathy. To establish novel experimental platforms which reproduce the cardiac phenotype of DMD patients, here we established iPS cell lines from T lymphocytes donated from two DMD patients, with a protocol using Sendai virus vectors. We successfully conducted the differentiation of the DMD patient-specific iPS cells into beating cardiomyocytes. DMD patient-specific iPS cells and iPS cell-derived cardiomyocytes would be a useful in vitro experimental system with which to investigate DMD cardiomyopathy.
Full-text · Article · Dec 2015 · International Heart Journal
[Show abstract][Hide abstract] ABSTRACT: -There are changes in the skeletal muscle of patients with chronic heart failure (CHF), such as volume reduction and fiber type shift toward fatigable type IIb fiber. FoxO signaling plays a critical role in the development of skeletal myopathy in CHF, and functional interaction between FoxO and the Wnt signal mediator β-catenin was previously demonstrated. We have recently reported that serum of CHF model mice activates Wnt signaling more potently than serum of control mice and that complement C1q mediates this activation. We therefore hypothesized that C1q-induced activation of Wnt signaling plays a critical role in skeletal myopathy via the interaction with FoxO.
-Fiber type shift toward fatigable fiber was observed in the skeletal muscle of dilated cardiomyopathy (DCM) model mice, which was associated with activation of both Wnt and FoxO signaling. Wnt3a protein activated FoxO signaling and induced fiber type shift toward fatigable fiber in C2C12 cells. Wnt3a-induced fiber type shift was inhibited by suppression of FoxO1 activity, whereas Wnt3a-independent fiber type shift was observed by overexpression of constitutively active FoxO1. Serum of DCM mice activated both Wnt and FoxO signaling and induced fiber type shift toward fatigable fiber in C2C12 cells. Wnt inhibitor and C1-inhibitor attenuated FoxO activation and fiber type shift both in C2C12 cells and in the skeletal muscle of DCM mice.
-C1q-induced activation of Wnt signaling contributes to fiber type shift toward fatigable fiber in CHF. Wnt signaling may be a novel therapeutic target to prevent skeletal myopathy in CHF.
No preview · Article · Jun 2015 · Circulation Heart Failure
[Show abstract][Hide abstract] ABSTRACT: Background:
We assessed radiographic kidney enhancement following an emergency coronary procedure as a predictor of contrast-induced nephropathy (CIN) and poor long-term outcome.
Methods and results:
We enrolled 126 consecutive patients who underwent an emergency coronary procedure and abdominal X-ray within 24h. We defined kidney enhancement as positive when the density of the kidneys was equal to or higher than that of the lumbar vertebrae. Of the 126 patients, 11 showed kidney enhancement and 115 did not. There were no significant differences in the baseline characteristics of patients with and without kidney enhancement. The incidence of CIN was significantly higher in patients with than in those without kidney enhancement (91% vs. 6%, P<0.01). During a mean follow-up of 21±16 months, 5 of 11 patients with kidney enhancement had poor outcomes, such as renal replacement therapy or death, whereas poor outcomes were observed in only 12 of 115 patients without kidney enhancement. Kaplan-Meier analysis revealed a significant difference in the probability of a poor outcome between patients with and those without kidney enhancement (46% vs. 10%, P<0.01).
Radiographic kidney enhancement following a percutaneous coronary procedure predicts the occurrence of CIN and poor clinical outcome.
No preview · Article · Dec 2012 · Circulation Journal
[Show abstract][Hide abstract] ABSTRACT: A 37-year-old Japanese woman experienced aborted sudden cardiac death from ventricular fibrillation and was diagnosed with Andersen-Tawil syndrome by genetic analysis that revealed 2 mutations in the KCNJ2 gene. Although she received an implantation of implantable cardioverter defibrillator and beta-blocker therapy, the frequency of premature ventricular contraction and bidirectional ventricular tachycardia did not decrease. Her ventricular arrhythmias increased after a full stomach test and a neostigmine provocation test, and reduced after cibenzoline administration, which indicates the relation with vagal tone. Moreover, increasing the pacing rate significantly decreased them. These findings indicate that the arrhythmia was bradycardia-dependent in this case.
No preview · Article · Jun 2012 · The American Journal of the Medical Sciences
[Show abstract][Hide abstract] ABSTRACT: Atrial fibrillation (AF) is observed in patients with Brugada syndrome (BS), especially those showing coved-type electrocardiogram (ECG) pattern. Using P-wave signal-averaged ECG (P-SAE), we investigated whether increased intraatrial conduction abnormality contributed to AF generation in BS patients.
Twenty BS patients and 20 age- and gender-matched healthy controls were enrolled. At the P-SAE recording, 12 of the 20 BS patients showed coved-type (C-BS) and eight showed saddleback-type (S-BS). The total duration (Ad) and root mean square voltage for the terminal 20 ms (LP(20) ) of the filtered P wave were measured. P-wave dispersion (P-disp) was defined as the difference between the maximum and minimum, measured from 16 precordial recording sites.
BS patients had a significantly longer Ad (128.2 ± 7.6 vs 116.3 ± 8.2 ms, P < 0.0001), lower LP(20) (2.6 ± 0.9 vs 3.4 ± 0.8 μV, P < 0.01), and greater P-disp (15.5 ± 7.0 vs 7.4 ± 3.2 ms, P < 0.0001) than the controls. C-BS patients had significantly longer Ad (131.0 ± 7.2 vs 124.1 ± 6.8 ms, P < 0.05) and lower LP(20) (2.2 ± 0.6 vs 3.2 ± 1.0 μV, P < 0.05) than S-BS patients. All C-BS patients and only three S-BS patients had atrial late potential (100% vs 38%, P < 0.01).
Intraatrial conduction delay and its heterogeneity may exist in BS patients, especially those showing coved-type ECG patterns. These atrial electrical abnormalities could be a substrate for atrial reentrant tachycardia such as AF.
No preview · Article · May 2011 · Pacing and Clinical Electrophysiology
[Show abstract][Hide abstract] ABSTRACT: We conducted a prospective study to determine whether a bolus injection of sodium bicarbonate before emergent coronary procedures in patients with chronic kidney disease (CKD) might prevent contrast-induced nephropathy (CIN). We enrolled 59 patients with CKD, defined by a serum creatinine concentration of >1.1 mg/dl or an estimated glomerular filtration rate of <60 ml/min, who were scheduled at admission to undergo an emergent coronary procedure. The patients were randomized to receive a bolus intravenous injection of 154 mEq/L of sodium bicarbonate (n = 30) or sodium chloride (n = 29) at the dose of 0.5 ml/kg, before contrast administration, followed by infusion of 154 mEq/L sodium bicarbonate at 1 ml/kg/hour for 6 hours in both groups. The primary end point was the occurrence of CIN, defined as an increase by > 25% or > 0.5 mg/dl of the serum creatinine level within 2 days after the procedure. In the sodium bicarbonate group, the serum creatinine concentration remained unchanged within 2 days of contrast administration (from 1.32 ± 0.46 to 1.38 ± 0.60 mg/dl, p = 0.33). In contrast, it had increased in the sodium chloride group (1.51 ± 0.59 to 1.91 ± 1.19 mg/dl, p = 0.006). The incidence of CIN was significantly lower in the sodium bicarbonate group than in the sodium chloride group (3.3% vs 27.6%, p = 0.01). In conclusion, rapid alkalization by bolus injection of sodium bicarbonate was effective for the prevention of CIN in patients with CKD undergoing emergent procedures.
No preview · Article · Feb 2011 · The American journal of cardiology
[Show abstract][Hide abstract] ABSTRACT: The Seattle Heart Failure Model (SHFM) is a validated prediction model that estimates the mortality in patients with chronic heart failure (CHF) using commonly obtained information, including clinical data, laboratory test results, medication use, and device implantation. In addition, cardiac iodine-123 meta-iodobenzylguanidine (MIBG) imaging provides prognostic information for patients with CHF. However, the long-term predictive value of combining the SHFM and cardiac MIBG imaging in patients with CHF has not been elucidated. To prospectively investigate whether cardiac iodine-123 MIBG imaging provides additional prognostic value to the SHFM in patients with CHF, we studied 106 outpatients with CHF who had radionuclide left ventricular ejection fraction < 40% (30 ± 8%). The SHFM score was obtained at enrollment, and the cardiac MIBG washout rate (WR) was calculated from anterior chest images obtained at 20 and 200 minutes after isotope injection. During a mean follow-up of 6.8 ± 3.5 years (range 0 to 13), 32 of 106 patients died from cardiac causes. A multivariate Cox analysis revealed that the WR (p = 0.0002) and SHFM score (p = 0.0091) were independent predictors of cardiac death. Kaplan-Meier analysis showed that patients with an abnormal WR (> 27%) had a significantly greater risk of cardiac death than did those with a normal WR for both those with a SHFM score of ≥ 1 (relative risk 3.3, 95% confidence interval 1.2 to 9.7, p = 0.01) and a SHFM score of ≤ 0 (relative risk 3.4, 95% confidence interval 1.2 to 9.6, p = 0.004). In conclusion, the cardiac MIBG WR provided additional prognostic information to the SHFM score for patients with CHF.
Full-text · Article · Feb 2011 · The American journal of cardiology