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Abstract The authors investigated the antihypertensive effect of sacubitril/valsartan (Sac/Val) when switching from other drugs and assessed whether brain natriuretic peptide (BNP) or plasma renin activity (PRA) before drug switching was a predictor of blood pressure lowering after switching to Sac/Val. In 92 patients with treated hypertension, clinic blood pressure, plasma BNP, and PRA were examined before and after switching to Sac/Val. Clinic systolic and diastolic blood pressures significantly decreased after drug switching to Sac/Val (p

Abstract Aims Oxidative stress plays an important role in the development and progression of heart failure (HF). Although exercise and oxidative stress are closely related, the effect of acute exercise on reactive oxygen species production and the fluctuation on prognosis are unclear. Methods and results We enrolled 94 patients who were hospitalized for worsening HF (mean age 68.0 ± 14.5 years old, 63.8% male). The changes in diacron‐reactive oxygen metabolites (d‐ROM) values, a marker of oxidative stress, before and after a cardiopulmonary exercise test were considered as Δd‐ROM. The mean follow‐up period was 24 ± 13 months, during which 15 patients had all‐cause death or left ventricular assist system implantation. Kaplan–Meier analysis demonstrated that all‐cause death or left ventricular assist system implantation was significantly higher in the Δd‐ROM‐positive group than in the Δd‐ROM‐negative group (log‐rank P = 0.047). Elevated Δd‐ROM levels were associated with increased mortality risk. Multivariate analysis adjusted for body mass index and peak oxygen uptake revealed that Δd‐ROM was an independent prognostic factor of adverse events (Tertile 3 vs. 1; hazard ratio: 4.57; 95% confidence interval: 1.21–29.77; P = 0.022). Conclusions Patients with HF who underwent a cardiopulmonary exercise test and had an increased oxidative stress marker level had a poor prognosis. The appropriate exercise intensity could be determined by evaluating the changes in oxidative stress status in response to acute exercise in patients with HF.

Introduction: Silent brain infarction (SBI) is an independent risk factor for subsequent symptomatic stroke in the general population. Although aortic stenosis (AS) is also known to be associated with an increased risk of future symptomatic stroke, little is known regarding the prevalence and risk factors for SBI in patients with AS. Methods: The study population comprised 83 patients with severe AS with no history of stroke or transient ischemic attack and paralysis or sensory impairment (mean age 75 ± 7 years). All patients underwent brain magnetic resonance imaging to screen for SBI and multidetector-row computed tomography to quantify the aortic valve calcification (AVC) volume. Comprehensive transthoracic and transesophageal echocardiography were performed to evaluate left atrial (LA) abnormalities, such as LA enlargement, spontaneous echo contrast, or abnormal LA appendage emptying velocity (

Subcutaneous implantable cardioverter-defibrillator implantation is known to be a safe procedure. However, inappropriate lead insertion can lead to serious complications. We present a case where an inappropriate lead placement resulted in puncturing the lung parenchyma, and successful management of the lead-related pneumothorax through thoracoscopic lead removal and partial lung resection. (Level of Difficulty: Intermediate.)

Background: Although intraplaque hemorrhage (IPH) has been identified as a key feature of rupture-prone plaques, noninvasive imaging-based features for its detection in coronary artery have not been clearly established. The aim of this study was to investigate the relationship of the ratio between the signal intensities of coronary plaque and cardiac muscle (PMR) on non-contrast T1-weighted imaging (T1WI) in magnetic resonance with IPH in the directional coronary atherectomy (DCA) specimens. Methods: Fifteen lesions from 15 patients, who underwent DCA and T1WI, were prospectively enrolled. The snap-frozen samples obtained by DCA were used for immunohistochemical staining against a protein specific to erythrocyte membranes (glycophorin A) and macrophages. The percentage of glycophorin A and macrophages was graded using a scale from 0 to 4, with higher scores indicating higher percentages. Results: PMR showed a strong positive correlation with glycophorin A scores (ρ = 0.772, p

Dipeptidyl peptidase-4 (DPP-4) inhibitors not only improve impaired glucose tolerance in diabetes, but also have pleiotropic extra-pancreatic effects such as preconditioning effect for myocardial ischemia-reperfusion injury. Here, we investigated the anti-remodeling effects of linagliptin, a DPP-4 inhibitor, by use of DPP-4-deficient rats.After the induction of myocardial infarction (MI), Fischer 344 rats with inactivating mutation of DPP-4 were orally administrated with a DPP-4 inhibitor, linagliptin (5 mg kg−1·day−1), or vehicle in drinking water for 4 weeks. Linagliptin did not affect hemodynamic status, body weight, and infarct size. In echocardiography, linagliptin tended to improve left ventricular (LV) systolic function, and significantly improved LV diastolic function, surprisingly. Interstitial fibrosis in marginal region and macrophage infiltration were significantly lower in the linagliptin group than those in the vehicle group. Fibrosis-related gene expressions, such as collagen I and transforming growth factor-β1 (TGF-β1), and inflammation-related expressions, such as macrophage chemotactic protein 1 and matrix metalloproteinase-2 (MMP-2), were significantly suppressed in marginal area of the linagliptin-treated rats compared with the vehicle rats. The TGF-β1 and MMP-2 protein levels were attenuated by linagliptin in DPP-4-deficient cardiac fibroblasts.Linagliptin can attenuate MI-induced cardiac remodeling via a DPP-4-independent pathway. Keywords: Dipeptidyl peptidase-4, Fibrosis, Left ventricular diastolic function, Macrophage, Myocardial infarction

Background: Although silent brain infarction is an independent risk factor for subsequent symptomatic stroke and dementia in patients with nonvalvular atrial fibrillation, little is known regarding differences in risk factors for silent brain infarction between patients with paroxysmal and persistent nonvalvular atrial fibrillation. Methods: This study population consisted of 190 neurologically asymptomatic patients (mean age, 64 ± 11 years) with nonvalvular atrial fibrillation (119 paroxysmal, 71 persistent) who were scheduled for catheter ablation. All patients underwent brain magnetic resonance imaging to screen for silent brain infarction prior to ablation. Transthoracic and transesophageal echocardiography was performed to screen for left atrial abnormalities (left atrial enlargement, spontaneous echo contrast, or left atrial appendage emptying velocity) and complex plaques in the aortic arch. Results: Silent brain infarction was detected in 50 patients (26%) [26 patients (22%) in paroxysmal vs. 24 patients (34%) in persistent, p = 0.09]. Multiple logistic regression analysis indicated that age and diabetes mellitus or chronic kidney disease (estimated glomerular filtration rate

Aims Acute decompensated heart failure (ADHF) can occur early after transcatheter aortic valve implantation (TAVI), but the risk factors or mechanisms associated with it have not been fully determined. This hypothesis-generating study aimed to investigate the clinical indices associated with the development of ADHF within 72 hours after TAVI and to improve procedural approaches for TAVI.Method and results In this single-centre hypothesis generating prospective observational study, we enrolled 156 consecutive patients with severe aortic stenosis who underwent TAVI between January 2016 and February 2018 at our institution. We set the primary endpoint as the new development of ADHF within 72 hours after TAVI, and clinical indices associated with it were evaluated using a multivariable logistic model. The median age of the patients was 83 (quartile range 80–86) years, 48 (30.8%) were men and the median Society of Thoracic Surgery-Predicted Risk of Mortality was 7.1 (range 5.2–10.4). Mitral stenosis (MS), defined as mean transmitral valve pressure gradient ≥5 mm Hg, was present in 15 (9.6%) patients. After TAVI, the invasive mean transaortic valve pressure gradient (mAVPG) decreased from 48 (36–66) to 7 (5–11) mm Hg, and 12 (7.7%) patients developed ADHF within 72 hours after TAVI. Multivariable logistic regression analysis showed that MS (adjusted OR, 14.227; 95% CI 2.654 to 86.698; p=0.002) and greater decreases in mAVPG (1.038; 1.003 to 1.080; p=0.044) were associated with ADHF.Conclusions MS and drastic improvement of mAVPG were associated with new development of ADHF within 72 hours after TAVI.

A-71-year-old woman was diagnosed as chronic thromboembolic pulmonary hypertension (CTEPH) accompanied by essential thrombocythemia (ET) with JAK2 V617F mutation. Blood test showed remarkable increase of platelet counts (132.9 × 10^4/μL) and elevated plasma BNP level (125.1pg/mL). Right heart catheterization (RHC) revealed remarkably high mean pulmonary arterial pressure (mPAP) of 43 mmHg. We gave her riociguat of 7.5mg, oral anticoagulants, oxygen inhalation for CTEPH, and anagrelide for ET. We performed 4 sessions of balloon pulmonary angioplasty (BPA) in 9 months RHC revealed successful hemodynamic improvement (mPAP = 21 mmHg) after final BPA procedure without riociguat. At six month later after final BPA procedure, RHC showed steadily improvement of mPAP (21 mmHg) without riociguat and oxygen inhalation. She lives well without oxygen inhalation and PH targeted therapy. This is the first report of successful treatment for a patient with CTEPH comorbid with ET with JAK2 V617F mutation by BPA.

Background: Tolvaptan is a vasopressin type 2 receptor antagonist used in heart failure (HF) with refractory diuretic resistance. However, since tolvaptan is also ineffective in some HF patients with reduced ejection fraction (HFrEF), the identification of responders is important. Methods: The study population consisted of 51 HFrEF patients who were administered tolvaptan (EF, 28 ± 7%). We defined responders as patients with a ≥50% increase in urine volume during the 24-hours after administration of tolvaptan. All patients underwent comprehensive transthoracic echocardiography before administration of tolvaptan. Patients were followed for 120 days to ascertain secondary events (cardiac death and rehospitalization for HF). Results: Multiple regression analysis indicated that right ventricular (RV) enlargement (defined as basal RV diameter > 41 mm and midlevel RV diameter > 35 mm, according to guidelines) remained a predictor of response after adjustment for age, sex, starting dosage of tolvaptan, and estimated glomerular filtration rate (odds ratio, 4.88; 95%-confidence interval, 1.26–18.9; P

Percutaneous treatment with carbon dioxide (CO2) mist, CO2 gas dissolved in water, contributes to improved cardiac function after myocardial infarction (MI). In this study, we investigated the effects of repeated pretreatment with CO2 mist on cardiac dysfunction after MI. The CO2 mist was generated by a dry mist production unit. The whole body of rats below the axilla was wrapped in a polyethylene bag, which was sealed and filled with the CO2 mist in the draft cabinet for 30 min daily for 7 days. MI was induced by ligation of the coronary artery in untreated (UT), CO2 gas-pretreated (CG), and CO2 mist-pretreated (CM) rats. The infarct size and the increase in oxidative stress due to MI were significantly smaller in the CM rats than in the UT rats. Furthermore, the expression of inflammation-related genes, such as monocyte chemoattractant protein-1, and fibrosis-related genes, such as transforming growth factor-β1, was significantly suppressed in the CM rats. The CM rats had a better left ventricular ejection fraction than the UT rats 7 days after MI. These parameters in the CG rats were the same as in the UT group. Thus, CO2 mist preparative treatment may be potentially useful for the reduction of MI.

BackgroundThe International Liaison Committee on Resuscitation (ILCOR) periodically updates the consensus recommendations for cardiopulmonary resuscitation to improve the outcomes of out‐of‐hospital cardiac arrest (OHCA). However, little is known about the differences in outcomes of witnessed OHCA following the publication of the ILCOR 2010 and the ILCOR 2005 recommendations. Methods and ResultsWe enrolled 241 990 adults who experienced witnessed OHCA between 2007 and 2013 from a prospective, nation‐wide, population‐based cohort database in Japan. We compared neurologically favorable 1‐month survival and 1‐month survival rates post‐OHCA by dividing the study period into 2 categories: the ILCOR 2005 period and ILCOR 2010 period. The associations between guideline periods and outcomes were estimated using multivariable logistic regression analysis and reported as adjusted odds ratio and 95% CI. Among 241 990 patients examined in this study, OHCA was witnessed in 44 706 patients (18%) by emergency medical service personnel and in 197 284 patients (82%) by citizens. Compared with the ILCOR 2005 period, the neurologically favorable 1‐month survival rate improved from 4.6% to 5.2% (adjusted odds ratio, 1.54; 95% CI, 1.42–1.67; P

BackgroundIn this study, we sought to investigate the 2‐year prognostic impact of B‐type natriuretic peptide (BNP) levels at discharge, following transcatheter aortic valve replacement. Methods and ResultsWe enrolled 1094 consecutive patients who underwent transcatheter aortic valve replacement between 2013 and 2016. Study patients were stratified into 2 groups according to survival classification and regression tree analysis (high versus low BNP groups). We evaluated the impact of high BNP on 2‐year mortality compared with that of low BNP using a multivariable Cox model, and assessed whether this stratification would improve predictive accuracy for determining 2‐year mortality by assessing time‐dependent net reclassification improvement and integrated discrimination improvement. The median age of patients was 85 years (quartile 82–88), and 29.2% of the study population were men. The median Society of Thoracic Surgeons score was 6.8 (4.7–9.5), and BNP at discharge was 186 (93–378) pg/mL. All‐cause mortality following discharge was 7.9% (95% CI, 5.8–9.9%) at 1 year and 15.4% (95% CI, 11.6–19.0%) at 2 years. The survival classification and regression tree analysis revealed that the discriminating BNP level to discern 2‐year mortality was 202 pg/mL, and that elevated BNP had a statistically significant impact on outcomes, with an adjusted hazard ratio of 2.28 (1.36–3.82, P=0.002). The time‐dependent net reclassification improvement (P=0.047) and integrated discrimination improvement (P=0.029) analysis revealed that the incorporation of BNP stratification with other clinical variables significantly improved predictive accuracy for 2‐year mortality. ConclusionsElevation of BNP at discharge is associated with 2‐year mortality after transcatheter aortic valve replacement.

Background: Although nifekalant hydrochloride (NIF) has been demonstrated to suppress ventricular tachyarrhythmias, especially electrical storms, the mechanism by which it does so is still unclear. We examined the effects of NIF on the spatial dispersion of repolarization (SDR) after implantable cardioverter-defibrillator (ICD) shock. Methods and Results: In 35 patients with oral amiodarone and β-blocker therapy, and an ICD, we recorded the 87-lead electrocardiogram during sinus rhythm (CONTROL-1 group) under general anesthesia, and just after the termination of induced ventricular fibrillation (VF) by ICD shock, with or without NIF administration. In all recordings, the corrected QT interval (QTc) was measured in each lead. The dispersion of QTc (QTc-D; maximum QTc minus minimum QTc) was also measured. Compared with that in the CONTROL-1 group, the QTc-D exhibited significant deterioration after ICD shock (61±14 and 90±19 ms1/2, respectively; p

Abstract.: Metabolic syndrome (MetS) induces serious complications; therefore, we developed a noninvasive MetS model using an extremely small minipig, the Microminipig. For 8 weeks, Microminipigs were administrated a high-fat and high-cholesterol diet (HFCD) for atherosclerosis and NG-nitro-l-arginine methyl ester (l-NAME) for inhibiting nitric oxide synthase. HFCD significantly increased serum low-density lipoprotein levels, l-NAME increased blood pressure and cardiac hypertrophy, and HFCD-induced aortal arteriosclerosis was accelerated by l-NAME administration. Endothelium-dependent relaxation of the coronary artery was remarkably decreased by l-NAME administration. This model may be useful for elucidating the mechanisms of MetS and developing new therapeutic medicines for its treatment. Keywords:: metabolic syndrome, Microminipig, nitric oxide

Tolvaptan, a non-peptide V2-receptor antagonist, is a newly developed diuretic agent. Recently, we reported that tolvaptan has diuretic as well as anti-inflammatory and anti-fibrotic actions in chronic heart failure. In this study, we investigated whether tolvaptan has a cardioprotective effect in acute heart failure after myocardial infarction (MI). After MI induction, rats were randomized into 6 groups as follows: vehicle group, group treated with 15 mg∙kg−1∙day−1 furosemide, 2 groups treated with 3 or 10 mg∙kg−1∙day−1 tolvaptan, and 2 groups treated with 15 mg∙kg−1∙day−1 furosemide combined with 3 or 10 mg∙kg−1∙day−1 tolvaptan. Each agent was administered for 2 weeks, and blood pressure levels and infarct sizes were similar in all MI groups. Lower left ventricular end-systolic volumes and greater improvement of left ventricular ejection fraction were observed in the tolvaptan-treated groups compared with the vehicle group. In contrast, furosemide alone did not improve them. Sirius red staining revealed that tolvaptan significantly repressed MI-induced interstitial fibrosis in the left ventricle. MI-induced mRNA expressions related to cardiac load, inflammation, and fibrosis were significantly attenuated in the combination group. The combination treatment also repressed MI-induced mineralocorticoid receptor expression. Tolvaptan, or combination of furosemide and tolvaptan, may improve cardiac function in acute MI. Keywords:: arginine vasopressin, acute myocardial infarction, diuretic, tolvaptan, cardiac remodeling

The purpose of this study was to examine the influence of the gravitation of the Moon on the frequency of births in Kyoto, Japan. A retrospective cohort analysis of 1007 consecutive births without the use of the induction agents was conducted on a population of births in a private midwife hospital from January, 1966 to December, 2000. There was a significant increase in the cases of births, when the gravitation of the Moon to the Earth was less than 31.5 N. Results of this study suggest that the gravitation of the Moon has an influence on the frequency of births.

Acute myocardial infarction (AMI) is a social burden. However, being able to predict AMI could lead to prevention. A previous study showed only the relation between the lunar phase and the occurrence of AMI, but the period it takes for the moon to orbit around the earth and the period of the lunar phase differ. This study investigated the effect of the gravitation of the moon on AMI. Data was comprised of 1369 consecutive patients with first AMI at 5 hospitals from October, 1984 to December, 1997. The universal gravitation of the moon was calculated and compared to the earth onset time of AMI. Universal gravitation of the moon was derived by G*m/d2 (G: universal gravitation constant, m: the mass of the moon, d: the distance between the center of the moon and the center of the earth). The relationship between m/d2 and the cases of AMI was determined. There was an increase in cases, when there is a distance of more than 399864 km from the center of the earth to the center of the moon. The gravitation of more than 399864 km was determined to be weaker gravitation. It is confirmed that the number of AMI patients significantly increases at weaker gravitation periods in this multicenter trial. In conclusion, these results suggest that the gravitation of the moon may have an influence on the occurrence of AMI.

Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of coved-type ST segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD) as a result of polymorphic ventricular tachyarrhythmia or ventricular fibrillation (VF). Data from large patient studies and a meta-analysis of previous reports have shown that patients with a history of syncope or SCD and a spontaneous type 1 Brugada ECG are at high risk for SCD. However, risk stratification of asymptomatic patients with Brugada type ECG is still a challenge. In particular, the use of electrophysiological study (EPS) for risk stratification remains controversial. Although some investigators have reported the possibility of use of EPS for distinguishing between high- and low-risk patients with Brugada type ECG, no precise predictor of risk for SCD in asymptomatic patients has yet been determined. The approach to treatment of these patients is thus still unclear. Large clinical prospective studies with uniform diagnostic criteria and protocols for EPS as well as extended follow-up periods of over ten years are required for prediction of SCD.

Long-acting Ca2+-channel blockers have been reported to be effective in treating ischemic heart disease. However, their effects on cardiac remodeling after myocardial infarction (MI) are still unclear. We performed this study to examine the effect of azelnidipine on left ventricular (LV) remodeling, including systolic and diastolic dysfunction, in rats with MI. MI was induced by ligation of the left anterior descending artery. The rats were then separated into 3 groups: a sham-operated group (n = 9), untreated MI group (n = 10), and azelnidipine-treated MI group (n = 10). Four weeks after MI, hemodynamic measurements and Doppler echocardiographic assessment were performed. LV weight and LV end-diastolic dimension were significantly higher in the untreated MI group than in the sham-operated group. Azelnidipine significantly prevented the increases in these parameters. Azelnidipine also improved the ejection fraction (42 ± 3%, P

The circulating endothelial progenitor cells (EPCs) have an important role in angiogenesis, and the smooth muscle progenitor cells (SMPCs) participate in atherosclerosis. However, little is known about the effects of treatment of diabetes mellitus (DM) on EPCs and SMPCs. Therefore, we investigated the relations between the number of circulating vasucular progenitor cells before and after the treatment for DM. Ten previously untreated DM patients were enrolled in this study. Blood samples were collected before and after treatment. The peripheral mononuclear cells were purified and cultured to differentiate them into EPCs and SMPCs. After two weeks, the number of EPCs was determined by Dil-labeled acetylated low density lipoprotein and lectin binding. The number of SMPCs was evaluated by immunocytochemical staining of α-smooth muscle actin. Before treatment, the number of EPCs and SMPCs was significantly related to hemoglobin A1c and blood sugar. Serial examination revealed that improvement of glycemic control significantly increased the number of both EPCs and SMPCs. DM reduces the number of circulating EPCs and SMPCs according to its severity, and treatment of DM significantly increases the number of EPCs and SMPCs, which may be involved in angiogenesis and atherosclerosis in diabetes. Keywords:: diabetes mellitus, endothelial progenitor cell, smooth muscle progenitor cell, glycemic control

In this study, we examined whether an angiotensin II type 1 (AT1)-receptor blocker improves diastolic heart failure (DHF) in Dahl salt-sensitive (DS) rats. DHF was prepared by feeding DS rats on 8% NaCl diet from 7 weeks of age. DHF was estimated with echocardiography by measuring E velocity / A velocity (E/A) of left ventricular inflow. DS rats with established DHF were orally given candesartan (1 mg/kg per day) or vehicle. After 13 days of treatment, candesartan significantly improved DHF, as shown by the reduction of E/A from 4.49 ± 1.04 to 1.98 ± 0.54 (P

Osteopontin has been reported to have an important role in cardiac fibrosis. However, little is known about the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin type 1 receptor blockers (ARB) on osteopontin expression in infarcted myocardium. The purpose of this study was to elucidate the effects of an ACEI (perindpril) and an ARB (candesartan cilexitil) on cardiac function as assessed by Doppler echocardiography and cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted rats. ACEI or ARB was administered after myocardial infarction (MI). At 4 weeks after MI, cardiac function, and mRNAs in non-infarcted myocardium were analyzed. ACEI and ARB equally prevented left ventricular dilatation, reduction of ejection fraction, and the increase in E/A wave velocity ratio and the rate of E wave deceleration by MI. ACEI and ARB significantly suppressed increased mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, osteopontin, and collagen I and III in the non-infarcted ventricle at 4 weeks. Immunohistochemically stained osteopontin was increased in interstitial fibrosis of non-infarcted myocardium. Both ACEI and ARB significantly prevented cardiac fibrosis and osteopontin expression. In conclusion, angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium and prevents cardiac remodeling after MI. Keywords:: osteopontin, renin-angiotensin system, cardiac remodeling, myocardial infarction

Because granulocyte-colony stimulating factor (G-CSF) mobilizes bone marrow cells including endothelial progenitor cells, we examined whether G-CSF augments angiogenesis and collateral vessel formation induced by bone marrow-mononuclear cells transplantation (BMT). Unilateral hindlimb ischemia was surgically induced in Lewis rats. One week after surgery, administration of 100 mg/kg per day G-CSF significantly increased the laser Doppler blood perfusion index (LDBPI), number of angiographically detectable collateral vessels (angiographic score), and capillary density determined by alkaline phosphatase staining. In the BMT group (1 × 107 cells/rat) and the group with combined G-CSF treatment and BMT, LDBPI was significantly increased compared with that in the vehicle-treated group. In the BMT group, neovascularization was significantly increased as evidenced by the angiographic score and capillary density compared with the vehicle-treated group. Furthermore, the combination of G-CSF treatment and BMT augmented neovascularization compared with BMT alone, as evidenced by the angiographic score and capillary density. Moreover, G-CSF significantly increased vascular endothelial growth factor mRNA and fibroblast growth factor-2 mRNA in hindlimb muscle. In conclusion, G-CSF was found to augment neovascularization in rat hindlimb ischemia. Combined use of G-CSF treatment and BMT may be a useful strategy for therapeutic neovascularization in ischemic tissues. Keywords:: granulocyte-colony stimulating factor, bone marrow-mononuclear cell transplantation, angiogenesis, hindlimb ischemia, endothelial progenitor cell

In this study, we investigated whether the Na+/Ca2+ exchanger (NCX) inhibitor SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy]phenoxy-5-ethoxyaniline) might have a protective effect against myocardial ischemia-reperfusion injury in rats. In particular, we focused on cardiac function using Doppler echocardiography and cardiac gene expression. We intravenously administered either SEA0400 and delivery vehicle or only the vehicle (as a control) to Wistar rats 5 min before ischemia was induced. Reperfusion was performed after 30 min of ischemia. At 1 week after ischemia-reperfusion injury, we assessed hemodynamics by inserting a polyethylene-tubing catheter, cardiac function by Doppler echocardiography, and myocardial mRNA expression was determined by Northern blot analysis. Left ventricular (LV) end-diastolic dimensions (LVDd) and LV end-diastolic volume (LVEDV) were significantly increased in the ischemia-reperfusion rat model group compared to the control group. The SEA0400-treated group had a significantly attenuated LVDd (P

Skeletal myoblast transplantation has therapeutic potential for repairing damaged heart. However, the optimal conditions for this transplantation are still unclear. Recently, we demonstrated that satellite cell-derived myoblasts lacking the MyoD gene (MyoD(-/-)), a master transcription factor for skeletal muscle myogenesis, display increased survival and engraftment compared to wild-type controls following transplantation into murine skeletal muscle. In this study, we compare cell survival between wild-type and MyoD(-/-) myoblasts after transplantation into infarcted heart. We demonstrate that MyoD(-/-) myoblasts display greater resistance to hypoxia, engraft with higher efficacy, and show a larger improvement in ejection fraction than wild-type controls. Following transplantation, the majority of MyoD(-/-) and wild-type myoblasts form skeletal muscle fibers while cardiomyocytes do not. Importantly, the transplantation of MyoD(-/-) myoblasts induces a high degree of angiogenesis in the area of injury. DNA microarray data demonstrate that paracrine angiogenic factors, such as stromal cell-derived factor-1 (SDF-1) and placental growth factor (PlGF), are up-regulated in MyoD(-/-) myoblasts. In addition, over-expression and gene knockdown experiments demonstrate that MyoD negatively regulates gene expression of these angiogenic factors. These results indicate that MyoD(-/-) myoblasts impart beneficial effects after transplantation into an infarcted heart, potentially due to the secretion of paracrine angiogenic factors and enhanced angiogenesis in the area of injury. Therefore, our data provide evidence that a genetically engineered myoblast cell type with suppressed MyoD function is useful for therapeutic stem cell transplantation.

The purpose of this study was to examine the influence of the gravitation of the Moon on the frequency of births in Kyoto, Japan. A retrospective cohort analysis of 1007 consecutive births without the use of the induction agents was conducted on a population of births in a private midwife hospital from January, 1966 to December, 2000. There was a significant increase in the cases of births, when the gravitation of the Moon to the Earth was less than 31.5 N. Results of this study suggest that the gravitation of the Moon has an influence on the frequency of births.