RESUMEN
In this paper a straightforward synthesis of a novel pyrazole derivative is reported. Prominent feature of this synthetic process is a 1,3-Dipolar Cycloaddition of a suitable nitrile imine with an activated α,ß-unsaturated lactam to afford directly and regioselectively the corresponding ring-fused pyrazole. Having obtained the central core of the synthetic target, a double stepwise functionalization with a "side chain" characterized by a terminal cyclic aliphatic amine was carried out. This molecular structure was designed to interact strongly with typical biological residues, and indeed it showed potent anticancer capability: in vitro cytotoxicity test on five different cancer cell lines showed interesting IC50 values in the range of 15-60 µM for exposure time of 24-72 h, thus resulting comparable with commercially available and nowadays therapeutically exploited anticancer compounds, such as 5-FU and NVP-BEZ235.
Asunto(s)
Antineoplásicos/síntesis química , Pirazoles/síntesis química , Aminoácidos Cíclicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Reacción de Cicloadición , Diseño de Fármacos , Humanos , Iminas/química , Lactamas/química , Nitrilos/química , Pirazoles/farmacologíaRESUMEN
A novel highly biocompatible nanosystem containing Mg nanoparticles is reported, characterized and tested as a suitable and non-toxic tool for photothermal therapy.
Asunto(s)
Materiales Biocompatibles/química , Hipertermia Inducida , Magnesio/química , Nanopartículas/química , Polímeros/química , Materiales Biocompatibles/uso terapéutico , Humanos , Rayos Láser , Magnesio/uso terapéutico , Micelas , Nanopartículas/uso terapéutico , Propiedades de SuperficieRESUMEN
Non-small cell lung cancer (NSCLC) accounts for â¼80% of all lung cancers. Although some advances in lung cancer therapy have been made, patient survival is still quite poor. Two microRNAs, miR-221 and miR-222, upregulated by the MET proto-oncogene, have been already described to enhance cell survival and to induce TNF-related apoptosis-inducing ligand (TRAIL) resistance in NSCLC cell lines, through the downregulation of p27(kip1), PTEN and TIMP3. Here, we further investigated this pathway and showed that miR-130a, expressed at low level in lung cancer cell lines, by targeting MET was able to reduce TRAIL resistance in NSCLC cells through the c-Jun-mediated downregulation of miR-221 and miR-222. Moreover, we found that miR-130a reduced migratory capacity of NSCLC. A better understanding of MET-miR-221 and 222 axis regulation in drug resistance is the key in developing new strategies in NSCLC therapy.
Asunto(s)
MicroARNs/genética , Proteínas Proto-Oncogénicas c-met/genética , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Regiones no Traducidas 3'/genética , Apoptosis/efectos de los fármacos , Apoptosis/genética , Sitios de Unión/genética , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Inhibidores de Cisteína Proteinasa/farmacología , Regulación hacia Abajo , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Mutación , Oligopéptidos/farmacología , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-met/metabolismo , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
AIMS: To report the implementation of cardiovascular secondary prevention guidelines following a cardiovascular event in Italy. METHODS AND RESULTS: Data were collected from 878 consecutive patients, who had suffered a cardiovascular event requiring hospitalisation in the preceding 12-24 months and who presented at 49 outpatient clinics across Italy. Cardiovascular risk markers were assessed through clinical examination, interview and reviewing of patients' charts; in addition, we collected information on changes in prevalence of selected risk factors that occurred since the time of index event. At the time of evaluation, increased body mass index (BMI) was observed in 35% of patients, with 20% being obese; 26% had diabetes and 21% uncontrolled hypertension. Although 91% of patients were on statins, no measurement of low-density lipoprotein (LDL)-cholesterol was available in the previous 6 months in 27% of patients and 16% had no knowledge of any lipid parameter in the same period. In the remaining patients, LDL was <100 mg dl(-1) in 57% and <70 mg dl(-1) in 20% of them. From the time of index event to interview, prevalence of uncontrolled hypertension remained stable, from 24% to 21% of patients; according to the patients' self-reporting, smoking had declined from 32% to 13% of patients and physical inactivity from 43% to 33% of patients. CONCLUSIONS: This survey shows, in a large national cohort, a suboptimal implementation of lifestyle changes and inadequate lipid control in patients at high cardiovascular risk after a cardiovascular event. Reinforcement of patients and physicians, implementation and adherence to guidelines is needed to reduce the burden of cardiovascular disease.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Guías como Asunto/normas , Prevención Secundaria/métodos , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Enfermedades Cardiovasculares/tratamiento farmacológico , LDL-Colesterol/sangre , Estudios Transversales , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Entrevistas como Asunto , Italia , Estilo de Vida , Masculino , Persona de Mediana Edad , Encuestas Nutricionales/métodos , Prevalencia , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
AIM: The aim of this study was to determine whether or not cardiac resynchronization therapy (CRT) has a favourable effect on the incidence of new-onset atrial fibrillation (AF) in a homogeneous population of patients with non-ischaemic idiopathic-dilated cardiomyopathy and severe heart failure. METHODS: We designed a single-centre prospective study and enrolled 58 patients AF naïve when received CRT. After 1 year of follow-up our population was subdivided into responders (72.4%) and non-responders (27.6%), so as to compare the incidence of AF after 1, 2 and 3 years of follow-up in these two groups. RESULTS: Already after 1 year, there was a significant (p < 0.05) difference in new-onset AF in non-responder patients with respect to responders (18.2% vs. 3.3%). These data were confirmed at 2 years (33.3% vs. 12.2%) and 3 years (50.0% vs. 15.0%) follow-up. In particular, 3 years after device implantation non-responders had an increased risk to develop new-onset AF (OR = 5.67). CONCLUSIONS: This is the first study analysing long-term effects of CRT in a homogeneous population of patients with non-ischaemic dilated cardiomyopathy, indicating the favourable role of this non-pharmacological therapy on the prevention of AF.
Asunto(s)
Fibrilación Atrial/prevención & control , Terapia de Resincronización Cardíaca , Cardiomiopatía Dilatada/complicaciones , Desfibriladores Implantables , Insuficiencia Cardíaca/terapia , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoAsunto(s)
Angioplastia Coronaria con Balón/métodos , Hemofilia A/complicaciones , Infarto del Miocardio/complicaciones , Infarto del Miocardio/cirugía , Enfermedad Aguda , Adulto , Factor VIII/administración & dosificación , Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Humanos , Masculino , Inhibidores de Agregación Plaquetaria/administración & dosificación , Resultado del TratamientoRESUMEN
Coronary flow reserve is a useful physiologic parameter providing information on coronary stenoses severity. To date, the gold standard to evaluate coronary flow reserve consists of fractional flow reserve (FFR) measurement, assessed with a pressure-wire. The FFR has a high lesion specificity, due to insensitivity to patient hemodynamic status and to coronary microvascular resistance; it shows low inter- and intraindividual variability and a well-defined, bound cut-off range values (0.75-0.80). Several reports confirmed that FFR has high reproducibility and feasibility in patients with either single- or multi-vessel coronary artery disease, or with both stable and instable coronary artery disease and that is significantly associated with patient outcome. More recently, the FFR has been used as a sensitive marker of successful percutaneous coronary intervention, since postprocedural FFR value strongly predicts patients event-free survival rate after angioplasty. Moreover, it has been demonstrated that abnormal FFR ratios can be also associated with diffused atherosclerotic coronary artery disease in the absence of unique angiographically detectable stenoses requiring revascularization. There are strong evidences supporting that the FFR provides crucial functional information that could be related with morphological endovascular ultrasound findings, with the possibility to achieve same information in a cheaper, easier and more available manner. This review will focus on the current available literature regarding coronary flow reserve quantification and its clinical validation, suggesting and highlighting its current and future clinical applications.
Asunto(s)
Enfermedad de la Arteria Coronaria/fisiopatología , Estenosis Coronaria/fisiopatología , Reserva del Flujo Fraccional Miocárdico , Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/terapia , Circulación Coronaria , Estenosis Coronaria/diagnóstico , Estenosis Coronaria/terapia , Estudios de Factibilidad , Humanos , Cómputos Matemáticos , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
The authors report, for the first time, immediate and mid-term outcome of early antiplatelet therapy discontinuation followed by uneventful non-cardiac surgery and endovascular aortic repair, few days after successful deployment of an endothelial progenitor cell capturing coronary stent, in three consecutive patients.
Asunto(s)
Vasos Coronarios , Células Endoteliales , Cuidados Preoperatorios , Células Madre , Stents , Anciano , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Factores de TiempoRESUMEN
BACKGROUND AND AIMS: Metabolic syndrome (MetS) was reported to be associated with increased cardiovascular risk in various settings, however its prognostic impact in peripheral arterial disease (PAD) is scanty. METHODS AND RESULTS: We prospectively studied 173 patients with intermittent claudication and ankle/brachial index (ABI)<0.90, in whom MetS was defined using the criteria of both the revised version of the Adults Treatment Panel III (rATP III) and the International Diabetes Federation (IDF). Of these patients, 52.6% met the rATP III and 54.9% the IDF criteria for MetS. During a median follow-up of 31 months, 54 cardiovascular events occurred. Kaplan-Meier curves showed a greater incidence of ischemic events in patients with MetS than in those without. However, adjusted Cox analyses revealed that only IDF-MetS was independently associated with increased cardiovascular risk (HR=1.91, 95% CI 1.03-3.51, p=0.038). Kaplan-Meier curves for the four groups of patients delineated according to the bootstrapped ABI cut-off value (0.73) and the presence or absence of IDF-MetS revealed that the syndrome improved the predictive power of ABI alone. Actually, among patients with an ABI≤0.73, those with IDF-MetS had a higher cardiovascular risk than those without the syndrome (HR=2.55, 95% CI 1.22-5.12, p=0.012). This was confirmed by c-statistic, which was 0.56 for ABI alone and increased to 0.65 (p=0.046) when IDF-Mets was added to the pressure index. CONCLUSION: In PAD, IDF-MetS, but not rATP III-MetS, is associated with an increased risk of cardiovascular events. Furthermore, IDF-MetS adds to the prognostic value of ABI, currently the most powerful prognostic indicator in PAD.
Asunto(s)
Índice Tobillo Braquial , Enfermedades Cardiovasculares/epidemiología , Claudicación Intermitente/complicaciones , Síndrome Metabólico/complicaciones , Anciano , Índice de Masa Corporal , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Circunferencia de la CinturaRESUMEN
OBJECTIVE: Obesity is an independent cardiovascular risk factor, but its prognostic role in patients with peripheral arterial disease (PAD) is not well defined. Accordingly, we assessed the impact of body mass index (BMI) and waist circumference (WC) on cardiovascular risk in a homogeneous cohort of PAD patients. METHODS: BMI and WC were measured in 190 consecutive PAD patients with ABI <0.90, referred to our university hospital for intermittent claudication. The occurrence of cardiac, cerebrovascular and peripheral events was prospectively assessed. The ability to classify risk was determined by calculating the hazard ratios (HRs) and c-statistics. RESULTS: During a median follow-up of 31.5 months, 63 patients (33.2%) had a cardiovascular event. Considered as continuous variables, both adiposity indices were significantly associated with increased cardiovascular risk, even after adjustment for possible confounding factors (HR=1.08, 95% CI 1.01-1.15, P=0.045 for BMI and HR=1.04, 95% CI 1.01-1.07, P=0.004 for WC). When BMI and WC were included together in a fully adjusted Cox model, the significant association between BMI and cardiovascular risk disappeared (HR=0.98, 95% CI 0.88-1.10, P=0.772), whereas WC remained significantly associated with a worse outcome (HR=1.04, 95% CI 1.01-1.08, P=0.033). The better discriminative ability of WC vs BMI was confirmed by the c-statistic, which was significantly higher for WC (0.63, 95% CI 0.56-0.70) than for BMI (0.56, 95% CI 0.51-0.63, P=0.038). CONCLUSIONS: Abdominal obesity and, to a lesser degree, general obesity worsen the prognosis of PAD patients independently of possible confounding factors. Weight reduction should be integrated in the active management of these patients.
Asunto(s)
Índice de Masa Corporal , Obesidad/complicaciones , Enfermedades Vasculares Periféricas/etiología , Circunferencia de la Cintura , Enfermedades Cardiovasculares/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad Abdominal/complicaciones , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de RiesgoRESUMEN
AIM: Insulin-like growth factor-1 (IGF-1) plays an important role in exercise physiology. We aimed the present study at assessing whether IGF-1 system and its changes with exercise are related to walking capacity in intermittent claudication (IC). METHODS: In 45 IC patients, blood samples for the measurement of IGF-1, IGF binding protein-3 (IGFBP-3), and acid labile subunit (ALS) were taken at rest and immediately after a treadmill exercise performed until initial claudication distance (ICD), i.e. until the occurrence of claudication pain in the affected limb. Control group consisted of 45 age- and sex-matched subjects without previous myocardial infarction or stroke. RESULTS: When IC patients were divided into two groups according to ICD value, ANOVA showed significant group differences for IGFBP-3 and ALS. Indeed, resting levels of IGFBP-3 were 3537+/-109 microg/L in controls, moderately lower (3399+/-204 microg/L) in IC patients with ICD >or= median, and markedly lower (2580+/-196 microg/L) in those with ICDAsunto(s)
Tolerancia al Ejercicio
, Factor I del Crecimiento Similar a la Insulina/metabolismo
, Claudicación Intermitente/sangre
, Claudicación Intermitente/fisiopatología
, Índice Tobillo Braquial
, Biomarcadores/sangre
, Proteínas Portadoras/sangre
, Estudios de Casos y Controles
, Distribución de Chi-Cuadrado
, Prueba de Esfuerzo
, Femenino
, Glicoproteínas/sangre
, Humanos
, Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina
, Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre
, Italia
, Modelos Logísticos
, Masculino
, Persona de Mediana Edad
, Caminata
RESUMEN
BACKGROUND: A comprehensive evaluation of comorbidity is important in predicting outcome of patients affected by a chronic disease because of the role of competing risk. AIM: To assess the prognostic impact of the Cumulative Illness Rating Scale (CIRS) on the cardiovascular risk of subjects participating in the Peripheral Arteriopathy and Cardiovascular Events (PACE) study. DESIGN: Prospective study. METHODS: The study included 60 patients with peripheral arterial disease (PAD) and 163 no-PAD subjects. CIRS-illness severity (IS) score and CIRS-comorbidity index (CI) were calculated. RESULTS: After a 42-month follow-up, 18/223 participants had a myocardial infarction or stroke. These subjects had a higher CIRS-IS score (1.99 +/- 0.52 vs. 1.71 +/- 0.37, P = 0.003) and a higher CIRS-CI (4.00 +/- 2.81 vs. 2.65 +/- 1.85, P = 0.005) vs. the 205 subjects without event. However, the significant association of CIRS scores with the outcome disappeared when conditions considered to be 'concordant' with the endpoint were excluded from the calculation of the scores. Importantly, among the 163 no-PAD subjects CIRS scores did not differ between those with and without an event. Conversely, in the 60 PAD patients, the CIRS-IS score calculated excluding the 'concordant' conditions was associated with an increased cardiovascular risk (RR = 4.03, 95% confidence interval (CI) 1.05-15.37, P = 0.042) after adjustment for potential confounders. The corresponding RR for the CIRS-CI was 1.43 (95% CI 1.03-1.98, P = 0.032). Furthermore, both CIRS scores improved the predictive value of ankle/brachial index, which is the most powerful prognostic indicator in PAD. CONCLUSION: Our findings indicate that overall comorbidity, and not only cardiovascular comorbidity, must be considered for prediction of myocardial infarction and stroke in PAD.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades Vasculares Periféricas/epidemiología , Anciano , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Infarto del Miocardio/epidemiología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUND: Human urotensin II is an 11-aminoacid peptide with a controversial role in the human cardiovascular system. Indeed, urotensin effects on vascular reactivity and in heart failure are well documented, while its potential role in the pathophysiology of athero-thrombosis is still unknown. This study investigates the effects of urotensin on tissue factor (TF) and VCAM-1/ICAM-1 expression in human coronary endothelial cells (HCAECs). METHODS AND RESULTS: Urotensin induced TF-mRNA transcription as demonstrated by real time PCR and expression of TF that was functionally active as demonstrated by procoagulant activity assay. In addition, urotensin induced expression of VCAM-1 and ICAM-1 as demonstrated by FACS analysis. VCAM-1 and ICAM-1 were functionally active because they increased leukocyte adhesivity to HCAECs. Urotensin-induced expression of TF and of VCAM-1/ICAM-1 was mediated through the Rho A-activation of the transcription factor, NF-kappaB, as demonstrated by EMSA. Indeed, lovastatin, an HMG-CoA reductase inhibitor, by modulating the Rho activation, and NF-kappaB inhibitors, suppressed the urotensin effects on TF and CAMs. CONCLUSIONS: Data of the present study, although in vitro, describe the close relationship existing between urotensin II and athero-thrombosis, providing for the first time support for the view that this peptide might have not only vasoactive functions but it might be an effector molecule able to induce a pro-atherothrombotic phenotype in cells of the coronary circulation. Although future studies are required to clarify whether these mechanisms are also important in the clinical setting, this report supports an emerging new role for urotensin II in the pathogenesis and progression of cardiovascular disease.
Asunto(s)
Moléculas de Adhesión Celular/genética , Vasos Coronarios/citología , Células Endoteliales/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Tromboplastina/genética , Urotensinas/farmacología , Enfermedades Cardiovasculares/etiología , Adhesión Celular , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Humanos , Molécula 1 de Adhesión Intercelular/genética , Leucocitos/citología , ARN Mensajero/biosíntesis , Molécula 1 de Adhesión Celular Vascular/genéticaRESUMEN
BACKGROUND: Inflammation plays a pivotal role in atherothrombosis. Recent data indicate that serum levels of neopterin, a marker of inflammation and immune modulator secreted by monocytes/macrophages, are elevated in patients with acute coronary syndromes and seem to be a prognostic marker for major cardiovascular events. The aim of the present study was to determine whether neopterin might affect the thrombotic and atherosclerotic characteristics of human coronary artery endothelial cells (HCAECs). METHODS AND RESULTS: In HCAECs, neopterin induced TF-mRNA transcription as demonstrated by real time polymerase chain reaction and expression of functionally active tissue factor (TF) as demonstrated by procoagulant activity assay, and of cellular adhesion molecules (CAMs) as demonstrated by FACS analysis, in a dose-dependent fashion. These neopterin effects were prevented by lovastatin, a HMG-CoA reductase inhibitor. Neopterin-induced TF and CAMs expression was mediated by oxygen free radicals through the activation of the transcription factor, nuclear factor-kappa B (NF-kappaB), as demonstrated by electrophoretic mobility shift assay and by suppression of CAMs and TF expression by superoxide dismutase and by NF-kappaB inhibitor, pyrrolidine-dithio-carbamate ammonium. CONCLUSIONS: These data indicate that neopterin exerts direct effects on HCAECs by promoting CAMs and TF expression and support the hypothesis that neopterin, besides representing a marker of inflammation, might be an effector molecule able to induce a pro-atherothrombotic phenotype in cells of the coronary circulation.
Asunto(s)
Vasos Coronarios/patología , Células Endoteliales/citología , Endotelio Vascular/patología , Neopterin/farmacología , Trombosis/patología , Adhesión Celular , Vasos Coronarios/citología , Relación Dosis-Respuesta a Droga , Humanos , Inflamación , Péptidos y Proteínas de Señalización Intercelular/metabolismo , FN-kappa B/metabolismo , Fenotipo , ARN Mensajero/metabolismo , Transcripción GenéticaRESUMEN
How beneficial is the adjunctive use of thrombectomy devices in STEMI patients undergoing primary angioplasty?
Asunto(s)
Infarto del Miocardio/terapia , Trombectomía/métodos , Angioplastia Coronaria con Balón/métodos , Cateterismo Cardíaco , Humanos , Revascularización Miocárdica/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Succión/métodos , Remodelación VentricularRESUMEN
BACKGROUND AND OBJECTIVES: Cigarette smoking is associated with an increased risk to develop myocardial infarction and ischemic stroke. However, the mechanisms responsible for these effects are still poorly understood. AIM: To investigate whether nicotine, the major component of cigarette smoking, and its main metabolite, cotinine, might induce a pro-thrombotic state via stimulation of tissue factor (TF) expression in two cell population widely represented in the arterial wall such as endothelial cells (ECs), and smooth muscle cells (SMCs). METHODS AND RESULTS: Incubation of ECs and SMCs with nicotine and cotinine induced TF expression in both cell types in a dose-dependent fashion, exerting its effect at the transcriptional level, as demonstrated by semiquantitative and by real-time PCR. Nicotine- and cotinine-induced TF expression was mediated by the activation of the transcription factor, nuclear factor-kappa B (NF-kappaB), as demonstrated by electrophoretic mobility shift assay and by the suppression of TF expression by the NF-kappaB inhibitor, pyrrolidine dithio carbamate ammonium. CONCLUSIONS: These data indicate that nicotine and cotinine exert direct effects on ECs and SMCs, shifting them toward a pro-thrombotic state via induction of TF expression. These effects on cells of the vessel wall might explain, at least in part, the deleterious cardiovascular consequences of cigarette smoking.
Asunto(s)
Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Nicotina/farmacología , Tromboplastina/genética , Animales , Secuencia de Bases , Células Cultivadas , Cotinina/farmacología , ADN Complementario/genética , Expresión Génica/efectos de los fármacos , Humanos , Infarto del Miocardio/etiología , FN-kappa B/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Conejos , Factores de Riesgo , Fumar/efectos adversos , Accidente Cerebrovascular/etiología , Trombosis/etiología , Transcripción Genética/efectos de los fármacosRESUMEN
Advances in anti-platelet therapy and improvement of stent deployment techniques have improved the safety and efficacy of stenting in the setting of ST-segment-elevation myocardial infarction (STEMI). However, in randomized trials, routine coronary stenting does not reduce mortality and re-infarction, compared to balloon angioplasty. Further, the benefits in target vessel revascularization seem to be reduced when applied to unselected patients with STEMI. Direct stenting represents an attractive strategy with potential benefits in terms of myocardial perfusion. Future large randomized trials are needed to evaluate whether this strategy has a significant impact on outcome, and to provide a cost-benefit analysis of the unrestricted use of drug-eluting stents in this high-risk subset of patients. The additional use of abciximab reduces mortality in primary angioplasty. Since the feasibility of long-distance transportation has been shown in several randomized trials, early pharmacological pre-treatment may confer further advantages by early recanalization and shorter ischaemic time, particularly in high-risk patients. Further randomized trials are needed to clarify the potential benefits from early abciximab administration and the potential role of small molecules in primary angioplasty for STEMI.
Asunto(s)
Angioplastia Coronaria con Balón/métodos , Anticuerpos Monoclonales/uso terapéutico , Anticoagulantes/uso terapéutico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Infarto del Miocardio/terapia , Inhibidores de Agregación Plaquetaria/uso terapéutico , Stents , Abciximab , Humanos , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/cirugía , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To assess effects on left ventricular (LV) function and on long term clinical outcome of late percutaneous transluminal coronary angioplasty (PTCA) of a chronically occluded infarct related artery. METHODS: 65 patients who underwent PTCA a mean (SD) of 6.0 (1.2) months after a previous myocardial infarction were divided in two groups according to dilated artery patency status after PTCA: group 1 (35 patients with TIMI (thrombolysis in myocardial infarction) grade 3 flow) and group 2 (30 patients with TIMI grade 0-2 flow). Echocardiography was performed at admission and at six months' follow up. A three year follow up was conducted with major adverse cardiac events (MACE) as end points. RESULTS: At follow up, group 1 had improved global LV ejection fraction (48.7% v 43.6%, p < 0.001) and LV indexed end diastolic and end systolic volumes (75 v 86 ml/m(2) and 40 v 53 ml/m(2), respectively, p = 0.011) compared with group 2. Kaplan-Meier analysis showed a higher incidence of cardiac death (p = 0.02) and MACE (p < 0.0001) in group 2. TIMI 3 after PTCA was an independent predictor of event-free survival at follow up. CONCLUSION: Late PTCA of a chronically occluded infarct related artery improves LV function, reduces cardiac death, and improves long term clinical outcome.
Asunto(s)
Estenosis Coronaria/terapia , Infarto del Miocardio/terapia , Disfunción Ventricular Izquierda/prevención & control , Angioplastia Coronaria con Balón/métodos , Angioplastia Coronaria con Balón/mortalidad , Angiografía Coronaria/métodos , Reestenosis Coronaria/prevención & control , Estenosis Coronaria/diagnóstico por imagen , Muerte Súbita Cardíaca/etiología , Supervivencia sin Enfermedad , Ecocardiografía/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Reperfusión Miocárdica/métodos , Reperfusión Miocárdica/mortalidad , Resultado del Tratamiento , Disfunción Ventricular Izquierda/diagnóstico por imagenRESUMEN
AIM: The aim of the present study was to evaluate [123I] MIBG uptake and clearance in patients with hypertrophic cardiomyopathy (HCM) and to assess their relationships with left ventricular function (systolic and diastolic) and perfusion. METHODS: Eleven consecutive patients with HCM (8 men and 3 women; mean age 38+/-12 years, none in the dilated phase) underwent (in separate days, in random order) [123I]-MIBG scintigraphy, [(99m)Tc]-MIBI SPET at rest, and echocardiography. All patients were studied in fasting condition, and all medications were discontinued. [(99m)Tc]-MIBI SPET study was performed 1 hour after tracer injection. [123I]-MIBG study was acquired 5 minutes (planar) and 4 hours (planar and SPET) after the i.v. injection of [123I]-MIBG. Heart to mediastinum ratio (H/M) was computed at 4 hours. Wash out rate (WOR) was computed as: (H early - H delayed)/(H early), after decay correction. Both [123I]-MIBG and [(99m)Tc]-MIBI SPET were analyzed on 3 short axis views (apical, middle, and basal). Left ventricular outflow tract gradient (LVOTG), ejection fraction, volumes, septum thickness, and left atrial fractional shortening (LAFS) were evaluated on echocardiography. RESULTS: [123I]-MIBG WOR showed a positive relationship with LVOTG (r=0.84, p<0.001) and septum thickness (r=0.76, p<0.01), while a negative one was found with LAFS (r= -0.66, p<0.05). The study group was divided into: Group A (n=5) with higher, and Group B (n=6) with lower WOR than the median value (i.e. 11%). Group A patients had significantly lower LAFS (17.6+/-4.8 vs 26.8+/-7.2%, p<0.05), higher LVOTG (49+/-35 vs 3+/-3 mmHg), and thicker septum (21+/-2 vs 17+/-2 mm) than Group B patients. Inferior and septal wall [123I]-MIBG uptake on 4 hour SPET was significantly lower in Group A than in Group B. On the other hand, no differences were found in (99m)T-MIBI SPET rest regional uptake between the 2 subgroups of patients. CONCLUSION: These results suggest that cardiac sympathetic activity correlates to cardiac anatomy (i.e. degree of hypertrophy) and diastolic function in patients with HCM.