RESUMEN
Doxorubicin (DOX) is widely used as an anti-cancer agent although it causes irreversible cardiomyopathy by increasing oxidative stress and deregulating nitric oxide production. Beraprost (BPS), a stable prostacyclin (PGI2) analog, is a potent vasodilator that has beneficial effects on myocardial ischemia. The objectives of the present study were to delineate the uncertain effects of prostcyclin therapy on DOX induced cardiomyopathy and to explore the mechanisms underlying PGI2 and DOX interaction. For this reason, we stimulated endogenous PGI2 production using bicistronic COX-1/PGIS gene transfer and BPS supplementation, and investigated the effects on DOX-induced cardiomyopathy. Caspase-dependent protein content, lactate dehydrogenase (LDH), DNA fragmentation, and TUNEL positive cells were elevated in DOX-treated cardiomyocytes. These indicators were further elevated by adenovirus-COX- 1/PGIS transfection or BPS supplementation. In addition, PGI2 overexpression further increased iNOS expression and superoxide accumulation in cardiomyocytes compared with DOX alone, which may be the reason for aggravated cytotoxicity. Moreover, BPS can induce cAMP response elements (CRE) binding to the iNOS promoter and phospho- cAMP response element binding protein (CREB) expression in a cyclic AMP-dependent manner. Our in vivo studies show that MnTBAP and aminoguanidine treatment of DOX and BPS co-administered in mice can attenuate caspase-3 and PARP-1 protein expression, and improve mouse survival, as observed in the iNOS gene-deleted mice. In conclusion, we demonstrated that BPS or adv-COX-1/PGIS increases PGI2 levels through iNOS expression and peroxynitrite production, via CREB protein phosphorylation; thereby aggravating DOX-mediated cardiotoxicity.
Asunto(s)
Apoptosis/efectos de los fármacos , Doxorrubicina/farmacología , Epoprostenol/análogos & derivados , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Prostaglandinas/agonistas , Animales , Proteína de Unión a CREB/metabolismo , Cardiomiopatías/metabolismo , Ciclooxigenasa 1/metabolismo , Epoprostenol/metabolismo , Epoprostenol/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Isquemia Miocárdica/metabolismo , Ácido Peroxinitroso/metabolismo , Fosforilación/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
BACKGROUND: No single precise qualitative method is recommended for evaluating the severity of aortic regurgitation (AR). Quantitative methods for AR assessment are, typically, cumbersome and time-consuming. The purpose of this study was to develop a more comprehensive method for predicting the severity of AR. METHODS: In all, 79 patients with normal left ventricular systolic function and at least mild AR were included in this prospective study. The standard references for evaluating AR severity were quantitative methods. The AR index consisted of 5 echocardiographic parameters: jet width ratio, vena contracta width, pressure half-time, jet density, and diastolic flow reversal in the descending aorta. Each parameter was scored on a 3-point scale from 1 to 3. The AR index was calculated as the sum of each score divided by the number of parameters. Thus, an increasing AR index score from 1 to 3 was indicative of increasing regurgitation. RESULT: The study demonstrated that the numeric value of AR index increased proportionately to the quantitative grading of AR severity, and proved to be an accurate predictor for AR severity. A 1.8 threshold for the AR index offered a high level of sensitivity and negative predictive value for severe AR. The possibility of missing severe AR was low with AR index less than 1.8. A 2.6 threshold for the AR index provided high specificity and positive predictive value for severe AR. The possibility of diagnosing severe AR was extremely high with AR index of 2.6 or more. CONCLUSION: AR index provided a more comprehensive method for predicting the degree of AR severity in this study. We suggest that the AR index should be considered for any evaluation of the severity of AR.
Asunto(s)
Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Disfunción Ventricular Izquierda/diagnóstico por imagen , Anciano , Insuficiencia de la Válvula Aórtica/clasificación , Insuficiencia de la Válvula Aórtica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia de la Válvula Mitral/clasificación , Insuficiencia de la Válvula Mitral/complicaciones , Pronóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Ultrasonografía , Disfunción Ventricular Izquierda/clasificación , Disfunción Ventricular Izquierda/etiologíaRESUMEN
Correlations derived for the relations between parasternal long-axis vena contracta width and effective regurgitant orifice area, regurgitant volume, and regurgitant fraction were highly significant. A vena contracta width of <3.0 or >5.0 mm provided excellent specificity for nonsevere and severe aortic regurgitation, respectively.
Asunto(s)
Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Ecocardiografía Doppler en Color , Anciano , Femenino , Humanos , Modelos Lineales , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
Percutaneous transluminal coronary angioplasty and stenting are established therapeutic modalities for coronary artery disease (CAD). Percutaneous transluminal septal myocardial ablation has become increasingly important for the treatment of symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). We report a case of HOCM combined with CAD involving the left anterior descending coronary artery. Coronary stent graft implantation was performed with uneventful recovery. Coronary stent graft implantation may be beneficial in selected cases of symptomatic HOCM combined with CAD.