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OBJECTIVE: To examine the Cardiac Rehabilitation Gifu Network (CR-GNet) feasibility in managing diseases and assisting patients in attaining physical fitness, and its impact on long-term outcomes after acute coronary syndrome (ACS). METHODS: In this prospective observational study, we enrolled 47 patients with ACS registered in the CR-GNet between February 2016 and September 2019. 37, 29, and 21 patients underwent follow-up assessments for exercise capacity (peak oxygen uptake) at 3 months, 6 months, and 1 year after discharge, respectively. Major adverse cardiac events (MACE) were compared with controls not registered in the CR-GNet. RESULTS: The coronary risk factors, except blood pressure, improved at 3 and 6 months, and 1 year after discharge. These risk factors in each patient significantly reduced from 2.9 at admission to 1.6, 1.4, and 1.9 at 3 months, 6 months, and 1 year after discharge (p<0.05), respectively. Peak oxygen uptake was significantly higher at 3 months (17.5±4.9 ml/kg/min), 6 months (17.9±5.1 ml/kg/min), and 1 year (17.5±5.5 ml/kg/min) after discharge than that at discharge (14.7±3.6 ml/kg/min) (p<0.05). During follow-up, there was no significant difference; MACE did not occur in any patients in the CR-GNet but occurred in controls. CONCLUSION: CR-GNet is a feasible option for the long-term management of ACS patients.
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BACKGROUND: Autophagy is a cellular process that degrades a cell's own cytoplasmic components for energy provision and to maintain a proper intracellular environment. Left ventricular reverse remodeling (LVRR) promises a better prognosis for patients with dilated cardiomyopathy (DCM). OBJECTIVES: The authors tested the hypothesis that autophagy is involved in LVRR and has prognostic value in the human failing heart. METHODS: Using left ventricular endomyocardial biopsy specimens from 42 patients with DCM (21 LVRR-positive and 21 LVRR-negative) and 7 patients with normal cardiac function (control), the authors performed immunohistochemistry and immunofluorescent labeling of LC3 and cathepsin D and electron microscopic observation in addition to general morphometry under light microscopy. RESULTS: The clinical characteristics of LVRR-positive patients were similar to those of the LVRR-negative patients, except for pulmonary artery pressure and left atrial dimension. Morphometry under light microscopy did not differ among specimens from DCM patients, regardless of their LVRR status. Electron microscopy revealed that autophagic vacuoles (autophagosomes and autolysosomes) and lysosomes were abundant within cardiomyocytes from DCM patients. Moreover, cardiomyocytes from LVRR-positive patients contained significantly more autophagic vacuoles with higher autolysosome ratios and cathepsin D expression levels than cardiomyocytes from LVRR-negative patients. Logistic regression analysis adjusted for age showed that increases in autophagic vacuole number and cathepsin D expression were predictive of LVRR. DCM patients who achieved LVRR experienced fewer cardiovascular events during the follow-up period. CONCLUSIONS: The authors show that autophagy is a useful marker predictive of LVRR in DCM patients. This provides novel pathologic insight into a strategy for treating the failing DCM heart.
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Autofagia , Cardiomiopatía Dilatada/patología , Insuficiencia Cardíaca/patología , Remodelación Ventricular , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Background: Kurort is a German term from the words kur (cure) and ort (area), and refers to improvements in patients' health in areas full of nature. We investigated the effect of kurort health walking in the 2 urban-style kurort health walking courses opened in Gifu City on systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, and mood. MethodsâandâResults: The subjects were 454 people (136 males, 318 females; mean [±SD] age 61.7±9.9 years) taking part in kurort health walking for the first time. SBP, DBP, and heart rate were measured before and after kurort health walking. Mood was assessed using a 10-item checklist after kurort health walking. Kurort health walking significantly decreased SBP and DBP and increased heart rate. The decrease in SBP was significantly greater in the SBP ≥140 than <140 mmHg group, indicating that SBP before Kurort health walking was inversely correlated with the change in SBP. Similarly, the decrease in DBP was significantly greater in the DBP ≥90 than <90 mmHg group, indicating that DBP before kurort health walking was also inversely correlated with the change in DBP. All 10 items on the mood assessment were significantly improved after kurort health walking. Conclusions: Kurort health walking preferentially decreases higher blood pressure and improves mood.
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Cardiología/normas , Enfermedades Cardiovasculares/terapia , Síndrome Mucocutáneo Linfonodular/terapia , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Consenso , Medicina Basada en la Evidencia/normas , Humanos , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/epidemiología , PronósticoRESUMEN
BACKGROUND: Because ST-elevation myocardial infarction (STEMI) extensively damages the heart, regenerative therapy with pluripotent stem cells such as multilineage-differentiating stress enduring (Muse) cells is required.MethodsâandâResults:In a first-in-human study, 3 STEMI patients with a left ventricular ejection fraction (LVEF) ≤45% after successful percutaneous coronary intervention received intravenously 1.5×107cells of a human Muse cell-based product, CL2020. The safety and efficacy on LVEF and wall motion score index (WMSI) were evaluated for 12 weeks. No adverse drug reaction was noted. LVEF and WMSI were markedly improved. CONCLUSIONS: The first-in-human intravenous administration of CL2020 was safe and markedly improved LV function in STEMI patients.
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Linaje de la Célula , Miocardio/patología , Células Madre Pluripotentes/trasplante , Regeneración , Infarto del Miocardio con Elevación del ST/cirugía , Volumen Sistólico , Función Ventricular Izquierda , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Células Madre Pluripotentes/metabolismo , Recuperación de la Función , Infarto del Miocardio con Elevación del ST/patología , Infarto del Miocardio con Elevación del ST/fisiopatología , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: This study aimed to investigate the effect of combination of high-salt intake and hypertension on renal functional and histological damage, associated with renal (pro)renin receptor [(P)RR] and AT1 receptor in rats. METHODS: Wistar Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) received regular rat chow (normal-salt diet 0.9%) or high-salt rat chow (high-salt diet 8.9%) for 6 weeks from 6 to 12 weeks of age. Systolic blood pressure, serum creatinine and blood urea nitrogen (BUN) were measured. Histological analysis of the kidney was performed. Western blot analysis was performed on the expressions of (P)RR, angiotensinogen and AT1 receptor in the kidney. RESULTS: High-salt intake significantly increased systolic blood pressure in WKYs and especially in SHRs. High-salt intake significantly increased serum creatinine and BUN, and accelerated renal tubulointerstitial fibrosis and glomerular sclerosis in SHRs. High-salt intake significantly enhanced the renal tissue expressions of (P)RR, angiotensinogen and AT1 receptor in SHRs. CONCLUSION: High-salt intake accelerates functional and histological renal damage associated with renal tissue overexpression of (P)RR and AT1 receptors in SHRs.
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Riñón/metabolismo , Riñón/patología , Receptor de Angiotensina Tipo 1/metabolismo , Receptores de Superficie Celular/metabolismo , Cloruro de Sodio Dietético/efectos adversos , Angiotensinógeno/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Nitrógeno de la Urea Sanguínea , Peso Corporal/efectos de los fármacos , Creatinina/sangre , Fibrosis , Glomeruloesclerosis Focal y Segmentaria/etiología , Glomeruloesclerosis Focal y Segmentaria/patología , Hipertensión/complicaciones , Masculino , Fosforilación , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Transducción de Señal/efectos de los fármacos , Cloruro de Sodio Dietético/administración & dosificación , Sístole , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Receptor de ProreninaAsunto(s)
Rehabilitación Cardiaca/normas , Terapia por Ejercicio/normas , Insuficiencia Cardíaca/rehabilitación , Rehabilitación Cardiaca/efectos adversos , Consenso , Terapia por Ejercicio/efectos adversos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Recuperación de la Función , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
We describe a 41-year-old man with a prior history of myocardial infarction, whose surface 12-lead electrocardiogram did not show typical left bundle-branch block pattern or wide QRS complex. However, electrophysiological study showed distinct left ventricular electrical conduction delays. The surface 12-lead electrocardiogram modified to the paper at 50â¯mm/s and double standard (20â¯mm equals 1â¯mV) revealed obvious notches of the terminal forces of the QRS in leads II, III, aVL, aVF, V3, V4, V5, and V6, these might be partially consistent with left ventricular electrical conduction delay in the scar lesion of the infero-posterior of the ventricle.
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Electrocardiografía , Infarto del Miocardio , Adulto , Bloqueo de Rama/diagnóstico , Sistema de Conducción Cardíaco , Ventrículos Cardíacos , Humanos , Masculino , Infarto del Miocardio/diagnósticoRESUMEN
BACKGROUND: Changes in the plasma adenosine concentration and the effects on left ventricular (LV) function and remodeling in patients with acute myocardial infarction (AMI) remain unclear. MethodsâandâResults: In 58 patients with AMI and 14 subjects without cardiac disease (controls), we measured the plasma adenosine concentration by LC-MS/MS. Blood samples were taken from the antecubital vein on days 0, 1, 7, and 14 after AMI, and from the controls on admission. Cardiac echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI. There were no significant differences in the plasma adenosine concentrations among days 0 (211.5±150.2 nmol/L), 1 (192.7±141.3 nmol/L), 7 (218.8±154.1 nmol/L), and the controls (136.0±50.9 nmol/L). The plasma adenosine concentration increased significantly on day 14 (321.1±195.4 nmol/L) after AMI as compared with days 0, 1 and 7. AMI patients with a greater increase in the plasma adenosine concentration in the subacute phase showed an attenuation of LV dilation in the chronic phase. The plasma adenosine concentration in the acute phase did not affect the LV ejection fraction in the chronic phase. CONCLUSIONS: The plasma adenosine concentration significantly increased 14 days after AMI, which may contribute to attenuation of LV dilation in the chronic phase.
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Adenosina/sangre , Dilatación , Infarto del Miocardio/fisiopatología , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Volumen Sistólico , Factores de TiempoRESUMEN
BACKGROUND: The (pro)renin receptor [(P)RR)] is involved in the activation of local renin-angiotensin system and subsequent development of cardiovascular disease. We investigated the therapeutic effect of a (P)RR blocker, handle-region peptide (HRP), on chronic kidney disease (CKD)-associated heart failure. METHODS AND RESULTS: CKD was induced in C57BL/6J mice by means of five-sixths nephrectomy. Eight weeks later, cardiac dysfunction and cardiac dilatation with hypertension developed. Mice were then assigned to 1 of the 3 following groups: vehicle, low-dose (0.01 mg·kg-1·d-1) HRP, or high-dose (0.3 mg·kg-1·d-1) HRP for 4 weeks. High-dose HRP treatment reversed left ventricular dilation and significantly improved cardiac dysfunction with ameliorated hypertension compared with the vehicle. The hearts with high-dose HRP treatment showed significant attenuation of cardiac fibrosis, cardiomyocyte hypertrophy, macrophage infiltration, and oxidative DNA damage. This treatment decreased the myocardial expressions of angiotensin (Ang) II, Ang II type 1 receptor, transforming growth factor ß1, extracellular matrix-related proteins, and lipid peroxidation. Autophagy was activated in the cardiomyocyte from nephrectomized mice, but HRP treatment had no effect on cardiomyocyte autophagy. CONCLUSIONS: This study indicates that (P)PR blockade is a beneficial strategy by suppressing cardiac fibrosis and hypertrophy to ameliorate heart failure caused by CKD.
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Insuficiencia Cardíaca/prevención & control , Oligopéptidos/administración & dosificación , Receptores de Superficie Celular/antagonistas & inhibidores , Insuficiencia Renal Crónica/complicaciones , Animales , Western Blotting , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Electrónica , Miocardio/ultraestructura , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/metabolismo , Receptor de ProreninaRESUMEN
P-wave signal-averaged electrocardiography (P-SAECG) can detect imperceptible conduction abnormalities, and volume analysis using two-dimensional speckle-tracking echocardiography (2-DSTE) allows us to easily measure the phasic function of the left atrium (LA). Both conduction abnormalities and functional deformation of the LA may be linked to the clinical outcome; however, the exact relationship is unclear. The aim of this study was to investigate the relationship between the phasic function of the LA and electrical conduction using P-SAECG and 2-DSTE. The subjects were 112 male volunteers (age 46.9 ± 13.2 years) with normal cardiac function who underwent P-SAECG and 2-DSTE. The filtered p-wave duration (FPD) and the root-mean-square voltage for the last 20 ms (RMS20) on P-SAECG wave were measured in ms and µV, respectively. Total emptying function (EF) (reservoir function), passive EF (conduit function), and active EF (booster pump function) of the LA were calculated as percentages to evaluate phasic LA function using 2DSTE. The mean FPD was 134.3 ± 11.7 ms and the mean RMS20 was 4.59 ± 2.39 µV. The mean total EF was 60.5 ± 13.1%, mean passive EF was 39.4 ± 13.9%, and mean active EF was 35.1 ± 13.9%. FPD had a negative correlation with passive EF (r = - 0.20, p = 0.039). FPD showed no significant relationship with total EF (r = - 0.03, p = 0.78) or active EF (r = 0.13, p = 0.18). There was a significant association between RMS20 and passive EF (r = 0.19, p = 0.048); however, no there was no correlation between RMS20 and total EF (r = 0.12, p = 0.23), or between RMS20 and passive EF (r = - 0.02, p = 0.86). In multivariate regression analysis, passive EF was an independent factor that influenced FPD duration. This study indicated that FPD was associated with conduit function, which includes phasic LA function. Therefore, electrical conduction of the LA and left ventricular diastolic function are closely related. In the clinical setting, when conduction abnormalities are detected, lifestyle measures or interventions can be applied to reduce cardiovascular risk.
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Ecocardiografía , Electrocardiografía , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Adulto , Diagnóstico por Imagen de Elasticidad , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Análisis de Regresión , Estudios RetrospectivosRESUMEN
We investigated whether combination therapy of G-CSF and erythropoietin (EPO)-liposome with Siaryl Lewis X (SLX) is more cardioprotective than G-CSF or EPO-liposome with SLX alone. For the purpose of generating myocardial infarction (MI), rabbits underwent 30 minutes of coronary occlusion and 14 days of reperfusion. We administered saline (control group, i.v.,), G-CSF (G group, 10 µg/kg/day × 5 days, i.c., starting at 24 hours after reperfusion), EPO-liposome with SLX (LE group, i.v., 2500 IU/kg EPO containing liposome with SLX, immediately after reperfusion), and G-CSF + EPO-liposome with SLX (LE + G group) to the rabbits. The MI size was the smallest in the LE+G group (14.7 ± 0.8%), and smaller in the G group (22.4 ± 1.5%) and LE group (18.5 ± 1.1%) than in the control group (27.8 ± 1.5%). Compared with the control group, the cardiac function and remodeling of the G, LE, and LE + G groups were improved, and LE + G group tended to show the best improvement. The number of CD31-positive microvessels was the greatest in the LE + G group, greater in the G and LE groups than in the control group. Higher expressions of phosphorylated (p)-Akt and p-ERK were observed in the ischemic area of the LE and LE + G groups. The number of CD34+/CXCR4+ cells was significantly higher in the G and LE + G groups. The cardiac SDF-1 was more expressed in the G and LE + G groups. In conclusion, Post-MI combination therapy with G-CSF and EPO-liposome with SLX is more cardioprotective than G-CSF or EPO-liposome with SLX alone through EPCs mobilization, neovascularization, and activation of prosurvival signals.
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Células Progenitoras Endoteliales/fisiología , Eritropoyetina/farmacología , Factor Estimulante de Colonias de Granulocitos/farmacología , Infarto del Miocardio/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Animales , Vasos Coronarios/citología , Vasos Coronarios/efectos de los fármacos , Modelos Animales de Enfermedad , Composición de Medicamentos/métodos , Quimioterapia Combinada/métodos , Ecocardiografía , Células Progenitoras Endoteliales/efectos de los fármacos , Eritropoyetina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Corazón/efectos de los fármacos , Liposomas , Masculino , Microvasos/citología , Microvasos/efectos de los fármacos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/etiología , Neovascularización Fisiológica/efectos de los fármacos , Oligosacáridos/química , Conejos , Regeneración/efectos de los fármacos , Antígeno Sialil Lewis X , Resultado del TratamientoRESUMEN
AIMS: Glucagon-like peptide-1 (GLP-1) is a neuroendocrine hormone secreted by the intestine. Its receptor (GLP-1R) is expressed in various organs, including the heart. However, the dynamics and function of the GLP-1 signal in heart failure remains unclear. We investigated the impact of the cardio-intestinal association on hypertensive heart failure using miglitol, an α-glucosidase inhibitor known to stimulate intestinal GLP-1 production. METHODS AND RESULTS: Dahl salt-sensitive (DS) rats fed a high-salt diet were assigned to miglitol, exendin (9-39) (GLP-1R blocker) and untreated control groups and treated for 11 weeks. Control DS rats showed marked hypertension and cardiac dysfunction with left ventricular dilatation accompanied by elevated plasma GLP-1 levels and increased cardiac GLP-1R expression as compared with age-matched Dahl salt-resistant (DR) rats. Miglitol further increased plasma GLP-1 levels, suppressed adverse cardiac remodelling, and mitigated cardiac dysfunction. In cardiomyocytes from miglitol-treated DS hearts, mitochondrial size was significantly larger with denser cristae than in cardiomyocytes from control DS hearts. The change in mitochondrial morphology reflected enhanced mitochondrial fusion mediated by protein kinase A activation leading to phosphorylation of dynamin-related protein 1, expression of mitofusin-1 and OPA-1, and increased myocardial adenosine triphosphate (ATP) content. GLP-1R blockade with exendin (9-39) exacerbated cardiac dysfunction and led to fragmented mitochondria with disarrayed cristae in cardiomyocytes and reduction of myocardial ATP content. In cultured cardiomyocytes, GLP-1 increased expression of mitochondrial fusion-related proteins and ATP content. When GLP-1 and exendin (9-39) were administered together, their effects cancelled out. CONCLUSIONS: Increased intestinal GLP-1 secretion is an adaptive response to heart failure that is enhanced by miglitol. This could be an effective strategy for treating heart failure through regulation of mitochondrial dynamics.
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Células Enteroendocrinas/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Insuficiencia Cardíaca/metabolismo , Íleon/metabolismo , Mitocondrias Cardíacas/metabolismo , Dinámicas Mitocondriales , Miocitos Cardíacos/metabolismo , 1-Desoxinojirimicina/análogos & derivados , 1-Desoxinojirimicina/farmacología , Animales , Células Cultivadas , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Dinaminas/metabolismo , GTP Fosfohidrolasas/metabolismo , Receptor del Péptido 1 Similar al Glucagón/antagonistas & inhibidores , Inhibidores de Glicósido Hidrolasas/farmacología , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Incretinas/farmacología , Masculino , Proteínas de la Membrana/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/patología , Dinámicas Mitocondriales/efectos de los fármacos , Proteínas Mitocondriales/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Comunicación Paracrina , Fragmentos de Péptidos/farmacología , Ratas Endogámicas Dahl , Ratas Sprague-Dawley , Transducción de Señal , Cloruro de Sodio Dietético , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
We examined whether the stimulation of the angiotensin II AT1 receptor increases the expression of the cardiac (pro)renin receptor ((P)RR) and its downstream signals and whether the blockade of the angiotensin II AT1 receptor by azilsartan decreases the expression of the cardiac (P)RR and its signaling in spontaneously hypertensive rats (SHRs) with a high-salt intake. Rats received normal-salt (0.9%) chow, high-salt (8.9%) chow, normal-salt chow with 1 mg/day of azilsartan, and high-salt chow with 1 mg/day of azilsartan from 6 to 12 weeks of age. Rats with normal-salt chow were administered 100 ng/kg/min of angiotensin II by osmotic minipump from 6 to 12 weeks of age. A high-salt diet and angiotensin II significantly increased the systolic blood pressure; overexpressed cardiac (P)RR, phosphorylated (p)-ERK1/2, p-p38MAPK, p-HSP27, and TGF-ß1; enhanced cardiac interstitial and perivascular fibrosis, cardiomyocyte size, interventricular septum (IVS) thickness, and left ventricular (LV) end-diastolic dimension; and decreased LV fractional shortening. Azilsartan decreased systolic blood pressure, cardiac expressions of (P)RR, p-ERK1/2, p-p38MAPK, p-HSP27, and TGF-ß1, cardiac interstitial and perivascular fibrosis, cardiomyocyte size, and LV diastolic dimension, and improved LV fractional shortening. In conclusion, azilsartan attenuates cardiac damage caused by high salt intake through the downregulation of the cardiac (pro)renin receptor and its downstream signals in SHRs.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bencimidazoles/farmacología , Presión Sanguínea/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Oxadiazoles/farmacología , Receptores de Superficie Celular/metabolismo , Cloruro de Sodio Dietético/efectos adversos , Angiotensina II , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Animales , Bencimidazoles/uso terapéutico , Corazón/efectos de los fármacos , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Miocardio/metabolismo , Oxadiazoles/uso terapéutico , Fosforilación/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Receptores de Superficie Celular/genética , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Receptor de ProreninaRESUMEN
BACKGROUND: The role of endogenous adenosine in cardiac patients is still unclear, so we investigated the relationship between the plasma adenosine concentration and left ventricular (LV) function, LV dilation and LV wall thinning in cardiac patients.MethodsâandâResults:In 97 cardiac patients, with angina pectoris, old myocardial infarction, dilated or hypertrophic cardiomyopathy, and valvular heart disease, plasma adenosine concentrations were measured using the LC-MS/MS system, and the LV function, LV end-diastolic dimension (LVDd), LV posterior wall thickness (LVPWth), and interventricular septum thickness (IVSth) were assessed by echocardiography. The plasma adenosine concentration was significantly higher in patients with a LV ejection fraction (EF), an indicator of the LV systolic function, <47% compared with those with LVEF ≥47% (P=0.027). There was no difference between the plasma adenosine concentration and E/e', an indicator of LV diastolic function. The plasma adenosine concentration was significantly higher in patients with LVDd ≥50 mm than in those with LVDd <50 mm (P=0.030). The plasma adenosine concentration was inversely correlated with IVSth (P=0.003) and LVPWth (P=0.0007). The plasma adenosine concentration was significantly higher in patients with IVSth <8 mm than in those with IVSth ≥8 mm (P=0.015), and was significantly higher in patients with LVPWth <8 mm than in those with LVPWth ≥8 mm (P=0.020). CONCLUSIONS: Endogenous adenosine may be related to LV dysfunction, dilation, and wall thinning in cardiac patients.
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Adenosina/sangre , Cardiomiopatía Dilatada/sangre , Miocardio/metabolismo , Disfunción Ventricular Izquierda/sangre , Anciano , Anciano de 80 o más Años , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miocardio/patología , Disfunción Ventricular Izquierda/patología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
RATIONALE: Multilineage-differentiating stress enduring (Muse) cells, pluripotent marker stage-specific embryonic antigen-3+ cells, are nontumorigenic endogenous pluripotent-like stem cells obtainable from various tissues including the bone marrow. Their therapeutic efficiency has not been validated in acute myocardial infarction. OBJECTIVE: The main objective of this study is to clarify the efficiency of intravenously infused rabbit autograft, allograft, and xenograft (human) bone marrow-Muse cells in a rabbit acute myocardial infarction model and their mechanisms of tissue repair. METHODS AND RESULTS: In vivo dynamics of Nano-lantern-labeled Muse cells showed preferential homing of the cells to the postinfarct heart at 3 days and 2 weeks, with ≈14.5% of injected GFP (green fluorescent protein)-Muse cells estimated to be engrafted into the heart at 3 days. The migration and homing of the Muse cells was confirmed pharmacologically (S1PR2 [sphingosine monophosphate receptor 2]-specific antagonist JTE-013 coinjection) and genetically (S1PR2-siRNA [small interfering ribonucleic acid]-introduced Muse cells) to be mediated through the S1P (sphingosine monophosphate)-S1PR2 axis. They spontaneously differentiated into cells positive for cardiac markers, such as cardiac troponin-I, sarcomeric α-actinin, and connexin-43, and vascular markers. GCaMP3 (GFP-based Ca calmodulin probe)-labeled Muse cells that engrafted into the ischemic region exhibited increased GCaMP3 fluorescence during systole and decreased fluorescence during diastole. Infarct size was reduced by ≈52%, and the ejection fraction was increased by ≈38% compared with vehicle injection at 2 months, ≈2.5 and ≈2.1 times higher, respectively, than that induced by mesenchymal stem cells. These effects were partially attenuated by the administration of GATA4-gene-silenced Muse cells. Muse cell allografts and xenografts efficiently engrafted and recovered functions, and allografts remained in the tissue and sustained functional recovery for up to 6 months without immunosuppression. CONCLUSIONS: Muse cells may provide reparative effects and robust functional recovery and may, thus, provide a novel strategy for the treatment of acute myocardial infarction.
Asunto(s)
Lisofosfolípidos/fisiología , Infarto del Miocardio/cirugía , Células Madre Pluripotentes/trasplante , Receptores de Lisoesfingolípidos/fisiología , Esfingosina/análogos & derivados , Aloinjertos , Animales , Autoinjertos , Diferenciación Celular , Movimiento Celular/fisiología , Factor de Transcripción GATA4/antagonistas & inhibidores , Factor de Transcripción GATA4/genética , Factor de Transcripción GATA4/fisiología , Supervivencia de Injerto , Proteínas Fluorescentes Verdes/análisis , Xenoinjertos , Humanos , Luciferasas/análisis , Proteínas Luminiscentes/análisis , Masculino , Infarto del Miocardio/patología , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , Pirazoles/farmacología , Piridinas/farmacología , Interferencia de ARN , ARN Interferente Pequeño/farmacología , Conejos , Receptores de Lisoesfingolípidos/antagonistas & inhibidores , Receptores de Lisoesfingolípidos/genética , Proteínas Recombinantes de Fusión/análisis , Especificidad de la Especie , Esfingosina/fisiología , Receptores de Esfingosina-1-FosfatoRESUMEN
PURPOSE: The purposes of this study were to investigate pulmonary vein cross-sectional orifice area (PV-CSOA) using intracardiac echocardiography (ICE) and to determine its association with atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). METHODS: We studied 77 patients undergoing initial RFCA for AF (55 paroxysmal and 22 persistent AF patients, mean age 61 ± 12 years, 59 men). The PV-CSOA was measured in each patient and expressed as an index divided by the body surface area-left superior (LSPV-CSOA), left inferior (LIPV-CSOA), right superior (RSPV-CSOA), and right inferior (RIPV-CSOA). RESULTS: After a mean follow-up of 21 ± 14 months, 61 patients maintained sinus rhythm (non-recurrence group) and AF recurred in 16 patients (recurrence group). The LSPV-CSOA index was significantly greater in the recurrence group compared with the non-recurrence group (146 ± 41 vs. 126 ± 30 mm2/m2, p = 0.04). A Cox regression multivariate analysis revealed that the LSPV-CSOA was the independent predictor of AF recurrence (HR 1.02, 95% CI 1.01-1.04, p = 0.01). The LSPV-CSOA cutoff value of 154 mm2/m2 predicts AF recurrence with 50% positive predictive value and 89% negative predictive value. CONCLUSIONS: The present study suggests that ICE can be used as an alternative imaging tools for assessing the PV-CSOA during RFCA and that the LSPV-CSOA index was a useful independent predictor of AF recurrence after RFCA.
Asunto(s)
Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Ecocardiografía/métodos , Técnicas Electrofisiológicas Cardíacas/métodos , Monitoreo Intraoperatorio/métodos , Venas Pulmonares/cirugía , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Ablación por Catéter/mortalidad , Estudios de Cohortes , Estudios Transversales , Femenino , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/cirugía , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Recurrencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: In patients with the long QT syndrome (LQTS), a sudden increase in heart rate can cause T-wave alternans (TWA) with beat-to-beat alternating polarity of T wave. We hypothesized that LQTS patients at high risk for torsades de pointes (TdP) may exhibit momentary atrial or sinoatrial premature beat-induced T-wave inversion (APB-TWI). OBJECTIVE: The purpose of this study was to assess the association of APB-TWI with TdP history and with microvolt TWA. METHODS: Twenty-four-hour continuous 12-lead electrocardiograms (ECGs) were recorded in 18 healthy subjects and 39 consecutive patients with LQTS types 1 (n = 21), 2 (n = 4), 3 (n = 4), and unidentified (n = 10). Peak TWA was determined by the modified moving average method. RESULTS: The 39 LQTS patients were divided into 2 groups: 10 LQTS patients with TdP history (TdP group) and 29 without (non-TdP group). None of the healthy subjects showed APB-TWI, whereas 38.5% of the LQTS patients (15/39) exhibited APB-TWI. The incidences of APB-TWI and TWA ≥42 µV were significantly higher in the TdP group than in the non-TdP group (APB-TWI: 80% vs 24.1%, P = .006; TWA ≥42 µV: 100% vs 65.5%, P = .04). APB-TWI was inferior in sensitivity for an association with TdP history to TWA ≥42 µV (80% vs 100%) but superior in specificity (75.9% vs 51.7%). Patients with APB-TWI exhibited significantly higher TWA values than those without [median (interquartile range) 73 (55-106.5) vs 48 (37.5-71.8) µV, P = .02]. CONCLUSION: APB-TWI is an easily measurable ECG pattern and is strongly associated with TdP history as well as TWA ≥42 µV in LQTS patients. APB-TWI and TWA may share pathophysiological mechanisms.
Asunto(s)
Complejos Atriales Prematuros/fisiopatología , Electrocardiografía , Frecuencia Cardíaca/fisiología , Síndrome de QT Prolongado/complicaciones , Adolescente , Adulto , Complejos Atriales Prematuros/epidemiología , Complejos Atriales Prematuros/etiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Japón/epidemiología , Síndrome de QT Prolongado/fisiopatología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenAsunto(s)
Fibrilación Atrial/fisiopatología , Aleteo Atrial/fisiopatología , Frecuencia Cardíaca , Venas Pulmonares/fisiopatología , Taquicardia Supraventricular/fisiopatología , Vena Cava Superior/fisiopatología , Potenciales de Acción , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Aleteo Atrial/diagnóstico , Aleteo Atrial/cirugía , Ablación por Catéter , Técnicas Electrofisiológicas Cardíacas , Femenino , Humanos , Venas Pulmonares/cirugía , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/cirugía , Vena Cava Superior/cirugíaRESUMEN
We present the case of a 62-year-old woman with levofloxacin-induced Torsade de Pointes, in whom microvolt T-wave alternans was measured during acute hospitalization and when QT interval was dynamically changing, illustrating a means for monitoring proarrhythmia.