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BACKGROUND: Atrial fibrillation (AF), which contributes to an increased risk of stroke, frequently remains undetected, suggesting an unmet need for easier and more reliable AF screening. The reports on screening AF using an Omron blood pressure (BP) monitor with an irregular heartbeat (IHB) detector show inconsistent results, so the aim of this study was to develop a novel algorithm to accurately diagnose AF with 3 BP measurements using an Omron automated BP monitor with IHB detector.MethodsâandâResults:In total, 303 general cardiac patients were included. Real-time single-lead ECG revealed AF in 44 patients. BP measurement was performed 3 times per patient using the Omron BP monitor HEM-907, and the number of IHBs detected was recorded. Based on these data, we developed the following algorithm: ≥1 IHB is detected during at least 2 of 3 BP measurements and the maximum number of IHBs detected is ≥2. Using this algorithm, we achieved a sensitivity of 95.5% and specificity of 96.5%, for diagnosing AF. CONCLUSIONS: The novel algorithm with 3 BP measurements using the Omron automated BP monitor with IHB detector showed high sensitivity and specificity for diagnosing AF in general cardiac patients.
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Algoritmos , Fibrilación Atrial/diagnóstico , Determinación de la Presión Sanguínea/instrumentación , Presión Sanguínea , Electrocardiografía/instrumentación , Frecuencia Cardíaca , Procesamiento de Señales Asistido por Computador , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/fisiopatología , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: The lipid component of coronary plaques is associated with their vulnerability. The aim of this study was to investigate which coronary risk factors were relevant in predicting serial changes in the lipid component of coronary plaques as evaluated by integrated backscatter intravascular ultrasound (IB-IVUS).MethodsâandâResults:We enrolled 104 patients who underwent IB-IVUS-guided percutaneous coronary intervention (PCI) and were followed up with repeat IB-IVUS 6 months later. We investigated the serial changes in the plasma lipoprotein levels and the percentage of the lipid component of coronary plaques on IB-IVUS. In the multivariate linear regression analysis, the low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol (L/H) ratio independently had a significant fixed effect with the percentage of the lipid component of coronary plaques at the time of PCI. In addition, the change in the L/H ratio at the 6-month follow-up was significantly associated with that in the lipid component of coronary plaques (regression coefficient, 9.645; 95% CI: 5.814-13.475; P<0.0001); furthermore, this change was also observed in patients with an LDL-C <100 mg/dL. CONCLUSIONS: The L/H ratio was the most relevant parameter in predicting the lipid component of coronary plaques. Furthermore, strict management of the L/H ratio may reduce this lipid component, even in patients with an LDL-C <100 mg/dL.
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HDL-Colesterol/sangre , LDL-Colesterol/sangre , Lípidos , Placa Aterosclerótica/química , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea , Análisis de RegresiónRESUMEN
Little is known about the outcome of catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) and a severely reduced left ventricular ejection fraction (LVEF). We aimed to clarify the effectiveness of catheter ablation of AF in patients with a severely low LVEF. This retrospective study included 18 consecutive patients with HF and an LVEF of ≤ 35 % who underwent catheter ablation of AF. We investigated the clinical parameters, echocardiographic parameters and the incidence of hospitalizations for HF. During a median follow-up of 21 months (IQR, 13-40) after the final procedure (9 with repeat procedures), 11 patients (61 %) maintained sinus rhythm (SR) (6 with amiodarone). The LVEF and NYHA class significantly improved at 6 months after the CA in 12 patients (67 %) who were in SR or had recurrent paroxysmal AF (from 25.8 ± 6.3 to 37.0 ± 11.7 %, P = 0.02, and from 2.3 ± 0.5 to 1.5 ± 0.7, P < 0.01, respectively) but not in patients who experienced recurrent persistent AF. The patients with SR or recurrent paroxysmal AF had significantly fewer hospitalizations for HF than those with recurrent persistent AF after the AF ablation (log-rank test; P < 0.01). Catheter ablation of AF improved the clinical status in patients with an LVEF of ≤ 35 %. A repeat ablation procedure and amiodarone were often necessary to obtain a favorable outcome.
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Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Sistema de Conducción Cardíaco/cirugía , Ventrículos Cardíacos/diagnóstico por imagen , Disfunción Ventricular Izquierda/complicaciones , Función Ventricular Izquierda/fisiología , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Ecocardiografía , Ecocardiografía Transesofágica , Electrocardiografía , Femenino , Estudios de Seguimiento , Sistema de Conducción Cardíaco/fisiopatología , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Sístole , Resultado del Tratamiento , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
Regulatory T cells (Tregs) play a crucial role in the negative regulation of immune responses. Recent studies suggest that Tregs are involved in the pathogenesis of atherosclerosis and myocarditis. Here, we investigated the involvement of Tregs on worsening heart failure (HF) in patients with reduced ejection fraction (HF-REF). The study population consisted of 32 HF-REF patients who were hospitalized for worsening HF, and 18 control subjects. Cardiac function was evaluated by echocardiography. A single venous blood sample was collected before discharge. Circulating T cells were evaluated by flow cytometry. Tregs were defined as CD4(+)CD25(+)Foxp3(+)T cells, and the correlations between the frequency of Tregs and CRP, IL-6 and several echoparameters were analysed. Furthermore, all HF-REF patients were followed up to 12 months from discharge to examine the predictors of recurrent hospitalization.In HF-REF patients, Tregs were significantly decreased (5.9 ± 1.4 versus 8.0 ± 2.2%, P < 0.01), while CD4(+)HLADR(+)T cells were increased (10.1 ± 5.4 versus 7.3 ± 3.1%, P < 0.05), compared with controls. Tregs were negatively correlated with left ventricular end-diastolic dimension, and levels of CRP and IL-6. Eleven of 32 HF-REF patients were rehospitalized for worsening HF within 12 months. Multivariate Cox regression analysis showed that CD4/CD8 and frequency of Tregs were independent predictors for recurrent hospitalization. Furthermore, HF-REF patients expressing under 6% Treg/CD4(+)T cells showed a significantly higher incidence of recurrent hospitalization for worsening HF within 12 months.Our data suggest that Tregs might be involved in the pathogenesis of decompensated HF, and may be a novel predictor of poor prognosis in HF-REF patients.
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Insuficiencia Cardíaca/inmunología , Ventrículos Cardíacos/fisiopatología , Inmunidad Celular , Volumen Sistólico/fisiología , Linfocitos T Reguladores/inmunología , Función Ventricular Izquierda , Anciano , Ecocardiografía , Estudios de Seguimiento , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , PronósticoRESUMEN
Background: Early detection of atrial fibrillation (AF) remains an unsolved challenge and because the greatest risk factor for AF is hypertension, blood pressure (BP) monitors with AF detectors have been developed. We evaluated the clinical performance of an irregular heartbeat (IHB) algorithm built into an A&D automated BP monitor for AF diagnosis. MethodsâandâResults: Each of the 239 enrolled patients underwent BP measurement 3 times using the A&D UM-212 with the IHB algorithm. Real-time 3-lead ECG was recorded using automated ECG analysis software. Independent of the ECG analysis software results, 2 cardiologists interpreted the ECG and made the final diagnosis. Of the 239 patients, 135 were in sinus rhythm, 31 had AF, and 73 had non-AF arrhythmias. The respective sensitivity, specificity, and accuracy of the IHB algorithm for AF diagnosis were 98.9%, 91.2%, and 92.2% for the per-measurement evaluation, and 96.8%, 95.7%, and 95.8% for the per-patient evaluation (3/3 positive measurements). The respective sensitivity, specificity, and accuracy of the ECG analysis software for AF diagnosis were 91.4%, 97.9%, and 97.1% for the per-measurement evaluation, and 77.4%, 99.5%, and 96.7% for the per-patient evaluation (3/3 positive measurements). Conclusions: The IHB algorithm built into an A&D automated BP monitor had high diagnostic performance for AF in general cardiology patients, especially when multiple measurements were obtained.
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Twelve-lead electrocardiography provides us the clue about the differential diagnosis between atrioventricular nodal reentrant tachycardia and atrioventricular reentrant tachycardia.
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Objective Home care is important in patients with heart failure (HF) in order to maintain their quality of life. A biomarker that can be measured noninvasively is needed to optimize the home care of patients with HF. Urinary angiotensinogen (uAGT) is an indicator of the intrarenal renin-angiotensin system activity, which may be augmented in HF. We hypothesized that uAGT might be a urinary biomarker in HF. Methods We measured uAGT by an enzyme-linked immunosorbent assay and uAGT normalized by urinary creatinine (uCr)-designated uAGT/uCr-at admission and discharge in 45 patients hospitalized for HF. Results We found that both uAGT/uCr [median (interquartile range): 65.5 (17.1-127.7) µg/g Cr at admission; 12.1 (6.0-37.0) µg/g Cr at discharge; p<0.01] and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels [5,422 (2,280-9,907) pg/mL at admission; 903 (510-1,729) pg/mL at discharge; p<0.01] significantly decreased between admission and discharge along with an improvement in patient's clinical status [New York Heart Association scores: 3 (3-4) at admission; 1 (1-1) at discharge; p<0.01]. The generalized least squares model revealed that the time course changes in uAGT/uCr also correlated with those in NT-proBNP levels between admission and readmission in five patients readmitted for HF. Conclusion The results indicated that the time course changes in uAGT/uCr correlated with those in the NT-proBNP levels in patients with HF who showed a clinical improvement. Further investigation and development of a kit for the rapid measurement of uAGT are needed to evaluate the clinical utility of uAGT as a biomarker in HF.
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Angiotensinógeno/orina , Biomarcadores/orina , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/orina , Monitoreo Fisiológico/métodos , Péptido Natriurético Encefálico/orina , Fragmentos de Péptidos/orina , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Sistema Renina-Angiotensina , Factores de TiempoRESUMEN
BACKGROUND: Both contact force monitoring (CFM) and unipolar signal modification (USM) are guides for ablation, which improve the efficacy of pulmonary vein isolation of atrial fibrillation. We sought to compare the outcomes of atrial fibrillation ablation guided by CFM or USM. METHODS: A total of 136 patients with paroxysmal atrial fibrillation underwent a circumferential pulmonary vein isolation using CF sensing ablation catheters and were randomly assigned to undergo catheter ablation guided by either CFM (CFM-guided group: n=70) or USM (USM-guided group: n=66). In the USM-guided group, each radiofrequency application lasted until the development of completely positive unipolar electrograms. In the CFM-guided group, a CF of 20 g (range, 10-30 g) and minimum force-time integral of 400 g were the targets for each radiofrequency application. The primary end point was freedom from any atrial tachyarrhythmia recurrence without antiarrhythmic drugs at 12-months of follow-up. RESULTS: The cumulative freedom from recurrences at 12-months was 85% in the USM-guided group and 70% in the CFM-guided group (P=0.031). The incidence of time-dependent and ATP-provoked early electrical reconnections between the left atrium and PVs, procedural time, fluoroscopic time, and average force-time integral, did not significantly differ between the 2 groups. The radiofrequency time for the pulmonary vein isolation was shorter in the USM-guided group than CFM-guided group but was not statistically significant (P=0.077). CONCLUSIONS: USM was superior to CFM as an end point for radiofrequency energy deliveries during the pulmonary vein isolation in patients with paroxysmal atrial fibrillation in terms of the 12-month recurrence-free rate. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000021127.
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Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Técnicas Electrofisiológicas Cardíacas/métodos , Atrios Cardíacos/fisiopatología , Sistema de Conducción Cardíaco/fisiopatología , Monitoreo Intraoperatorio/métodos , Cirugía Asistida por Computador/métodos , Fibrilación Atrial/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Venas Pulmonares/cirugía , Resultado del TratamientoRESUMEN
Ultrasonic destruction of microbubbles (US/MB) in the microcirculation causes local inflammatory cell infiltration, which has been shown to induce angiogenesis. Granulocyte colony-stimulating factor (G-CSF), which mobilizes myelomonocytic cells from the bone marrow and enhances vascular endothelial growth factor (VEGF) release from these cells, has also been applied to therapeutic angiogenesis induction. In the present study, we sought to examine the potential of G-CSF pretreatment to enhance the angiogenic effect of US/MB. Ischemic hindlimbs in mice were treated with either a predetermined minimal effective dose (300 mug/kg) of G-CSF, US/MB alone or G-CSF pretreatment followed by US/MB at seven days after removal of the femoral artery. Ultrasonic destruction of microbubbles was performed as intermittent pulsed local insonation using a diagnostic ultrasound scanner at a peak negative pressure of 1.4 MPa after intravenous injection of perfluorocarbon microbubbles. At 21 days after the treatment, we quantified the surface vascularity using a grid method and the capillary density using an alkaline phosphatase stain. Relative to the capillary density in normal muscle, the capillary density in the treated limbs was restored to 74 +/- 13% by G-CSF alone and 90 +/- 20% by US/MB alone (p < 0.05 vs. both untreated and G-CSF alone), and further increased to 101 +/- 21% by G-CSF pretreatment. The collateral growth induced by the combination of G-CSF pretreatment and US/MB was 2.8- and 1.4-fold greater than the growth induced by G-CSF alone and US/MB alone, respectively (p < 0.05 for both). Thus, pretreatment with a single minimal effective dose of G-CSF can augment the angiogenic effect of US/MB.
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Inductores de la Angiogénesis/farmacología , Factor Estimulante de Colonias de Granulocitos/farmacología , Isquemia/terapia , Neovascularización Fisiológica/efectos de los fármacos , Terapia por Ultrasonido/métodos , Inductores de la Angiogénesis/uso terapéutico , Animales , Capilares/patología , Terapia Combinada , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Miembro Posterior/irrigación sanguínea , Isquemia/tratamiento farmacológico , Isquemia/patología , Isquemia/fisiopatología , Ratones , Ratones Endogámicos C57BL , Microburbujas , Proteínas RecombinantesRESUMEN
BACKGROUND: Cardiac rupture is an important cause of death in the acute phase after myocardial infarction (MI). Macrophages play a pivotal role in cardiac remodeling after MI. Apoptosis inhibitor of macrophage (AIM) is secreted specifically by macrophages and contributes to macrophage accumulation in inflamed tissue by maintaining survival and recruiting macrophages. In this study, we evaluated the role of AIM in macrophage accumulation in the infarcted myocardium and cardiac rupture after MI. METHODS AND RESULTS: Wild-type (WT) and AIMâ/â mice underwent permanent left coronary artery ligation and were followed-up for 7 days. Macrophage accumulation and phenotypes (M1 pro-inflammatory macrophage or M2 anti-inflammatory macrophage) were evaluated by immunohistological analysis and RT-PCR. Matrix metalloproteinase (MMP) activity levels were measured by gelatin zymography. The survival rate was significantly higher (81.1% vs. 48.2%, P<0.05), and the cardiac rupture rate was significantly lower in AIMâ/â mice than in WT mice (10.8% vs. 31.5%, P<0.05). The number of M1 macrophages and the expression levels of M1 markers (iNOS and IL-6) in the infarcted myocardium were significantly lower in AIMâ/â mice than in WT mice. In contrast, there was no difference in the number of M2 macrophages and the expression of M2 markers (Arg-1, CD206 and TGF-ß1) between the two groups. The ratio of apoptotic macrophages in the total macrophages was significantly higher in AIMâ/â mice than in WT mice, although MCP-1 expression did not differ between the two groups. MMP-2 and 9 activity levels in the infarcted myocardium were significantly lower in AIMâ/â mice than in WT mice. CONCLUSIONS: These findings suggest that AIM depletion decreases the levels of M1 macrophages, which are a potent source of MMP-2 and 9, in the infarcted myocardium in the acute phase after MI by promoting macrophage apoptosis, and leads to a decrease in the incidence of cardiac rupture and improvements in survival rates.
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Proteínas Reguladoras de la Apoptosis/deficiencia , Rotura Cardíaca Posinfarto/epidemiología , Macrófagos/metabolismo , Infarto del Miocardio/metabolismo , Receptores Inmunológicos/deficiencia , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/genética , Modelos Animales de Enfermedad , Femenino , Rotura Cardíaca Posinfarto/genética , Rotura Cardíaca Posinfarto/metabolismo , Incidencia , Interleucina-6/genética , Interleucina-6/metabolismo , Macrófagos/inmunología , Masculino , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Infarto del Miocardio/genética , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Receptores Inmunológicos/genética , Receptores Depuradores , Tasa de SupervivenciaRESUMEN
OBJECTIVE: We investigated the contribution of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species (ROS) generation to the pathogenesis of diastolic heart failure (DHF) in Dahl salt-sensitive (DS) hypertensive rats, with the aim of testing our hypothesis that the cardioprotective effects of angiotensin II (Ang II) blockade are provided by the suppression of this pathway. METHODS: DS rats were maintained on high (H: 8.0% NaCl) or low (L: 0.3% NaCl) salt diets from age 7 to 17 weeks. DS/H rats were also treated with candesartan cilexetil (10 mg/kg per day, orally) or a superoxide dismutase mimetic, tempol (3 mmol/l in drinking water) from age 7 to 17 weeks. RESULTS: DS/H rats represented hypertension, left ventricular (LV) relaxation abnormality and myocardial stiffening with preserved systolic heart function. As compared with DS/L rats, DS/H rats showed higher levels of transforming growth factor-beta (TGF-beta), connective tissue growth factor (CTGF), p22phox and gp91phox mRNA expression, NADPH oxidase activity and thiobarbituric acid-reactive substance (TBARS) contents in LV tissues. Gene expression of uncoupling protein-2 (UCP-2), an inner mitochondrial membrane proton transporter, was also 2.8 +/- 0.5-fold higher. In DS/H rats, treatment with candesartan did not alter blood pressure, but resulted in a marked improvement of the hemodynamic deterioration; these therapeutic effects were accompanied by decreases in myocardial NADPH oxidase activity, TBARS contents and the expression of TGF-beta, CTGF, p22phox, gp91phox and UCP-2. Similar therapeutic effects were provided by treatment with tempol in DS/H rats. CONCLUSIONS: Our data suggest that NADPH oxidase-mediated ROS production contributes to the pathogenesis of DHF in DS hypertensive rats, and that the cardioprotective effects of AngII blockade are, at least partially, mediated through the suppression of this pathway.
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Angiotensina II/fisiología , Insuficiencia Cardíaca/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Disfunción Ventricular Izquierda/metabolismo , Animales , Presión Sanguínea/fisiología , Colágeno/metabolismo , Factor de Crecimiento del Tejido Conjuntivo , Diástole/fisiología , Expresión Génica , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Hipertensión/fisiopatología , Proteínas Inmediatas-Precoces/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Canales Iónicos , Pulmón/patología , Masculino , Proteínas de Transporte de Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Miocardio/metabolismo , NADPH Oxidasas/metabolismo , Péptido Natriurético Encefálico/metabolismo , Tamaño de los Órganos/fisiología , Ratas , Ratas Endogámicas Dahl , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Proteína Desacopladora 2 , Disfunción Ventricular Izquierda/patología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
Excessive beta-adrenergic stimulation causes cardiac toxicity, which also contributes to cardiac oxidative stress. Although uncoupling protein 2 (UCP2), a member of the mitochondrial inner membrane carrier family, can regulate energy efficiency and oxidative stress in mitochondria, little data exist regarding interactions between UCP2 expression and beta-adrenergic stimulation induced cardiac oxidative damage. We investigated whether chronic beta-adrenergic stimulation induces myocardial energy metabolism abnormality via oxidative stress, including any role of UCP2. We also examined whether 3-methyl-1-phenyl-2-pyrazolin-5-one (MIC-186; edaravone), a potent free radical scavenger, has cardioprotective effects against beta-adrenergic stimulation. Male Sprague-Dawley rats received isoproterenol (1.2 mg/kg/day) subcutaneously or/and edaravone (30 mg/kg/day) orally. Isoproterenol increased the heart/body weight ratio, accompanied by an increase in the level of myocardial thiobarbituric acid reactive substances (TBARS) and a decreased phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. Isoproterenol also markedly increased expressions of UCP2 mRNA (1.74 fold vs. non-isoproterenol) and protein (1.93 fold vs. non-isoproterenol). Edaravone had no apparent effect in hypertrophic responses, but significantly prevented both increases in TBARS and decreases in the PCr/ATP ratio. Edaravone also prevented increases in UCP2 mRNA (0.76 fold vs. isoproterenol) and protein (0.62 fold vs. isoproterenol) expressions against isoproterenol administration. Our results suggest that chronic beta-adrenergic stimulation induces myocardial energy inefficiency via excessive oxidative stress. The antioxidant effect of edaravone has potential to improve energy metabolism abnormalities against beta-adrenergic stimulation. Adequate regulation of UCP2 expression through artificial reduction of oxidative stress may play an important role in protection of the myocardial energy metabolism.
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Agonistas Adrenérgicos beta/efectos adversos , Antioxidantes/farmacología , Antipirina/análogos & derivados , Cardiotónicos/farmacología , Proteínas de Transporte de Membrana/biosíntesis , Proteínas Mitocondriales/biosíntesis , Miocardio/metabolismo , Animales , Antipirina/farmacología , Edaravona , Metabolismo Energético/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Canales Iónicos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Proteína Desacopladora 2RESUMEN
Left ventricular (LV) dilatation following myocardial infarction (MI) is a major determinant of the patient's prognosis, and myocardial energy metabolism may play a key role in LV remodeling. We aimed to investigate the relative timing of LV dilatation to LV function, myocardial energy regulation by uncoupling protein (UCP)-2, and cellular damage in the noninfarct zone. Myocardial infarction was produced in Sprague-Dawley rats by ligation of the coronary artery. The LV end-diastolic dimension (mm) increased (8.9+/-0.3 vs 6.8+/-0.8 in sham-operated rats, P<0.01) in association with elevation of the LV end-diastolic pressure (mmHg) (18+/-5 vs 6+/-2 in sham-operated rats) at 1 week following the ligation. At 4 weeks, the UCP-2 expression (180% of that in sham-operated rats) and LV end-diastolic dimension increased further (11.1+/-0.5, P<0.01) but there was no change in the LV end-diastolic pressure. The mechanisms for LV dilatation were quite different between the early and late stages after MI. In the late stage, augmentation of UCP-2 expression in the noninfarct zone may be related to the LV dilatation. Further examinations regarding the possibility of the protective role of UCP-2 are needed.
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Canales Iónicos/metabolismo , Proteínas Mitocondriales/metabolismo , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Disfunción Ventricular Izquierda/metabolismo , Remodelación Ventricular , Animales , Northern Blotting , Modelos Animales de Enfermedad , Ecocardiografía , Hemodinámica , Canales Iónicos/genética , Masculino , Mitocondrias Cardíacas/metabolismo , Proteínas Mitocondriales/genética , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Miocardio/patología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Proteína Desacopladora 2 , Regulación hacia Arriba , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
BACKGROUND: The impact of nicorandil as adjunctive therapy for percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) is controversial. We performed 15O-labeled water positron emission tomography (PET) to quantify regional myocardial perfusion in patients with STEMI who received nicorandil or no adjunctive therapy during PCI. METHODS: PCI was performed within 8 h after STEMI onset in 33 patients. 14 patients received intracoronary nicorandil 2 mg immediately after recanalization of the culprit lesion (Nico group). After 3-4 weeks, PET was performed in which myocardial blood flow (MBF) was measured at baseline and during adenosine triphosphate (ATP)-induced hyperemia. Myocardial vascular resistance (MVR) was calculated for all segments. Data were obtained from the reperfused (Rep) and normal segments (Cont) in each patient. RESULTS: In patients not given nicorandil (No-Nico group), the MBF was significantly lower in Rep than that in Cont at baseline and during hyperemia (Cont vs. Rep: 0.82 ± 0.14 vs. 0.68 ± 0.11, P = 0.001, ATP-Cont vs. ATP-Rep: 2.00 ± 0.72 vs. 1.52 ± 0.61, P = 0.017), which was restored in the Nico group (Cont vs. Rep: 0.79 ± 0.17 vs. 0.78 ± 0.20; ATP-Cont vs. ATP-Rep: 2.02 ± 0.84 vs. 1.84 ± 0.62). MVR was elevated in Rep at baseline and during hyperemia in the No-Nico group. MVR elevation in Rep was prevented in the Nico group. CONCLUSIONS: 15O-labeled water PET was feasible for segmental analysis of MBF during the subacute phase of STEMI. It revealed that intracoronary administration of nicorandil to STEMI patients who underwent PCI prevented MVR elevation and thus restored MBF in the reperfused segments to a level similar to that in the normal segments.
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OBJECTIVES: The aim of this study was to evaluate the impact of olmesartan on progression of coronary atherosclerosis. BACKGROUND: Prior intravascular ultrasound (IVUS) trial results suggest slowing of coronary atheroma progression with some medicines but have not shown convincing evidence of regression with angiotension-II receptor blocking agents. METHODS: A prospective, randomized, multicenter trial-OLIVUS (Impact of OLmesartan on progression of coronary atherosclerosis: evaluation by IntraVascular UltraSound)-was performed in 247 stable angina pectoris patients with native coronary artery disease. When these patients underwent percutaneous coronary intervention for culprit lesions, IVUS was performed in their nonculprit vessels (without angiographically documented coronary stenosis [<50%]). Patients were randomly assigned to receive 10 to 40 mg of olmesartan or control and treated with a combination of beta-blockers, calcium channel blockers, diuretics, nitrates, glycemic control agents, and/or statins per physician's guidance. Serial IVUS examinations (baseline and 14-month follow-up) were performed to assess coronary atheroma volume. Volumetric IVUS analyses included lumen, plaque, vessel volume, percent atheroma volume (PAV), percent change in total atheroma volume (TAV) and PAV. RESULTS: Patient characteristics and blood pressure control were identical between the 2 groups. However, follow-up IVUS showed significantly decreased TAV and percent change in PAV in the olmesartan group (5.4% vs. 0.6 % for TAV and 3.1% vs. -0.7% for percent change in PAV, control vs. olmesartan, p < 0.05 for all). CONCLUSIONS: These observations suggest a positive role in a potentially lower rate of coronary atheroma progression through the administration of olmesartan, an angiotension-II receptor blocking agent, for patients with stable angina pectoris.