RESUMEN
Achilles tendinopathy is a common overuse condition affecting the adult population. The incidence is on the rise because of greater participation of people in recreational or competitive sporting activities. There are several treatment options available both non-operative and operative. Ultrasound-guided dry needling and high-volume image-guided injection is relatively a new procedure. The aim of this study was to find out the effectiveness of dry needling and HVIGI in the management of mid-portion chronic Achilles tendinopathy by performing a literature review. Search strategy was devised to find the suitable articles for critical appraisal using the electronic databases. Four articles were selected for critical appraisal, and these papers showed good short- to long-term results of image-guided high-volume injection in the management of Achilles tendinopathy. We conclude that high-volume image-guided injection is effective in the management of Achilles tendinopathy. It provides good short- and medium-term relief of symptoms. It should be considered as one of the many options available for this condition.
Asunto(s)
Tendón Calcáneo , Terapia por Acupuntura/métodos , Anestésicos Locales/administración & dosificación , Trastornos de Traumas Acumulados/complicaciones , Tendinopatía/terapia , Adulto , Enfermedad Crónica , Trastornos de Traumas Acumulados/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intralesiones , Masculino , Dimensión del Dolor , Recuperación de la Función , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tendinopatía/diagnóstico por imagen , Tendinopatía/etiología , Resultado del Tratamiento , Ultrasonografía Intervencional/métodosRESUMEN
Vesicular glutamate transporters (VGLUT1-3) carry glutamate into synaptic vesicles. VGLUT3 has been reported to be localized in nonglutamatergic neuronal populations in the brain. However, detailed subcellular localization of VGLUT3 has not been shown. In particular, the identity of synaptic vesicles expressing VGLUT3 remains to be revealed. Here we present novel electron microscopic postembedding immunogold data from mouse and rat brains showing that small, clear, and round synaptic vesicles in γ-aminobutyric acid (GABA)-ergic nerve terminals contain labeling for both VGLUT3 and the vesicular GABA transporter (VGAT). Immunoisolation of synaptic vesicles confirmed the immunogold data and showed vesicular colocalization of VGLUT3 and VGAT. Moreover, we show that gold particles signaling VGLUT3 are present in synaptic vesicles in acetylcholinergic nerve terminals in the striatum. Quantitative immunogold analyses reveal that the density of VGLUT3 gold particles is similar in GABAergic terminals in the hippocampus and the neocortex to that in cholinergic terminals in the striatum. In contrast to in the hippocampus and the neocortex, VGLUT3 was absent from VGAT-positive terminals in the striatum. The labeling pattern produced by the VGLUT3 antibodies was found to be specific; there was no labeling in VGLUT3 knockout tissue, and the observed labeling throughout the rat brain corresponds to the known light-microscopic distribution of VGLUT3. From the present results, we infer that glutamate is released with GABA from inhibitory terminals and acetylcholine from cholinergic terminals.
Asunto(s)
Sistemas de Transporte de Aminoácidos Acídicos/metabolismo , Encéfalo/metabolismo , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/metabolismo , Sistemas de Transporte de Aminoácidos Acídicos/deficiencia , Sistemas de Transporte de Aminoácidos Acídicos/ultraestructura , Animales , Encéfalo/citología , Colina O-Acetiltransferasa/metabolismo , Regulación de la Expresión Génica/genética , Proteínas Fluorescentes Verdes/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Inmunoelectrónica , Ratas , Ratas Wistar , Vesículas Sinápticas/metabolismo , Vesículas Sinápticas/ultraestructura , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/ultraestructuraRESUMEN
Glutamine plays multiple roles in the CNS, including metabolic functions and production of the neurotransmitters glutamate and GABA. It has been proposed to be taken up into neurons via a variety of membrane transport systems, including system A, which is a sodium-dependent electrogenic amino acid transporter system. In this study, we investigate glutamine transport by application of amino acids to individual principal neurons of the medial nucleus of the trapezoid body (MNTB) in acutely isolated rat brain slices. A glutamine transport current was studied in patch-clamped neurons, which had the electrical and pharmacological properties of system A: it was sodium-dependent, had a non-reversing current-voltage relationship, was activated by proline, occluded by N-(methylamino)isobutyric acid (MeAIB), and was unaffected by 2-aminobicyclo-[2.2.1]-heptane-2-carboxylic acid (BCH). Additionally, we examined the expression of different system A transporter isoforms using immunocytochemical staining with antibodies raised against system A transporter 1 and 2 (SAT1 and SAT2). Our results indicate that both isoforms are expressed in MNTB principal neurons, and demonstrate that functional system A transporters are present in the plasma membrane of neurons. Since system A transport is highly regulated by a number of cellular signaling mechanisms and glutamine then goes on to activate other pathways, the study of these transporters in situ gives an indication of the mechanisms of neuronal glutamine supply as well as points of regulation of neurotransmitter production, cellular signaling and metabolism in the native neuronal environment.
Asunto(s)
Sistema de Transporte de Aminoácidos A/metabolismo , Vías Auditivas/metabolismo , Glutamina/metabolismo , Neuronas/metabolismo , Rombencéfalo/metabolismo , Animales , Vías Auditivas/citología , Membrana Celular/metabolismo , Membrana Celular/ultraestructura , Inmunohistoquímica , Neuronas/efectos de los fármacos , Técnicas de Cultivo de Órganos , Técnicas de Placa-Clamp , Prolina/metabolismo , Prolina/farmacología , Isoformas de Proteínas/metabolismo , Ratas , Ratas Wistar , Rombencéfalo/citología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Bloqueadores de los Canales de Sodio/farmacología , beta-Alanina/análogos & derivados , beta-Alanina/farmacologíaRESUMEN
The utilization of stress echocardiography has undergone considerable expansion and evolution over the past three decades. Although stress echocardiography was first conceived as a noninvasive diagnostic tool for determining the presence or absence of coronary artery disease (CAD), its prognostic value is now well established. Thus, identification of patients at risk for future cardiac events has become a primary objective in the noninvasive evaluation of patients with chest pain syndromes and among patients with known CAD. In particular, the ability of stress echocardiography to identify patients at low (<1%), intermediate (1-5%) or high (>5%) risk for future cardiac events is essential to patient management decisions. Moreover, previous studies have conclusively demonstrated the incremental prognostic value of stress echocardiography over clinical and treadmill exercise data, in predicting future cardiac events. This review addresses the current role and summarizes current literature with respect to the use of stress echocardiography in determining patient risk for cardiac events and the cost-effective integration of such information into patient management decisions.
Asunto(s)
Dolor en el Pecho/diagnóstico por imagen , Dolor en el Pecho/economía , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/economía , Ecocardiografía de Estrés/economía , Dolor en el Pecho/diagnóstico , Enfermedad de la Arteria Coronaria/diagnóstico , Análisis Costo-Beneficio , Humanos , Ciudad de Nueva York , Evaluación de Resultado en la Atención de Salud , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Insulin and glucagon secretion from the islets of Langerhans is highly regulated. Although an increased plasma glucose level is the major stimulus for insulin exocytosis, roles for glutamine and glutamate have been suggested. Interestingly, the islet cells display elements associated with synaptic transmission. In the central nervous system (CNS), glutamine transport by SN1 and SAT2 sustain the generation of neurotransmitter glutamate. We hypothesized that the same transporters are essential for glutamine transport into the islet cells and for subsequent formation of glutamate acting as an intracellular signaling molecule. We demonstrate that islet cells express several transporters which can mediate glutamine transport. In particular, we show pronounced expression of SN1 and SAT2 in B-cells and A-cells, respectively. The cell-specific expression of these transporters together with their functional characteristics suggest an important role for glutamine in the regulation of insulin secretion.
Asunto(s)
Acetiltransferasas/biosíntesis , Sistemas de Transporte de Aminoácidos Neutros/biosíntesis , Células Secretoras de Glucagón/metabolismo , Glutamina/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Acetiltransferasas/genética , Sistemas de Transporte de Aminoácidos Neutros/genética , Animales , Transporte Biológico , Secreción de Insulina , Ratones , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To determine the seasonal variation of the commonly isolated bacterial pathogens in stool samples. MATERIAL AND METHODS: A retrospective descriptive study was undertaken of all the stool samples submitted from within Karachi to the Aga Khan University Hospital Laboratory over a period of five years (January 1997- December 2001) in order to determine the commonly isolated bacterial pathogens and to predict their seasonal variation. RESULTS: A total of 16379 stool samples were included in this review. Bacterial isolates were found in 6670 stool samples (culture detection rate=40.7%). The mean age at the time of culture of each sub-group was < or = 1 year group (6.58 +/- 3.1 months), 1-5 years (2.13 +/- 0.94 years), 5-14 years (8.3 +/- 2.6 yrs) and adults (43.2 +/- 18.5 years). Male: Female ratio was 1.2:1. Vibrio cholera 01 Ogawa (32.8%), Campylobacter jejuni (17.3%), Enteropathogenic Escherichia coli (9.9%), Salmonella paratyphi b (6.6%) and Shigella flexneri (6.2%) were the most common organisms isolated. These organisms show a distinct seasonal variation with summer predilection. CONCLUSION: In contrast to the previous studies from South Asia, which have identified E. coil, followed by Vibrio cholerae as the most common enteric isolates, we found Vibrio cholera 01 Ogawa followed by Campylobacter jejuni as the most common enteric pathogens isolated in an urban setting. It is important to consider seasonal variation when empirically treating diarrheal diseases in our region.
Asunto(s)
Bacterias/aislamiento & purificación , Heces/microbiología , Estaciones del Año , Adolescente , Adulto , Niño , Preescolar , Diarrea/microbiología , Femenino , Gastroenteritis/microbiología , Humanos , Lactante , Masculino , Pakistán , Estudios RetrospectivosRESUMEN
UNLABELLED: Human studies have suggested that Doppler transesophageal echocardiography (TEE) can determine normal physiologic coronary blood flow (CBF) and alterations in CBF due to proximal flow-limiting stenoses. However, assessment of CBF by Doppler TEE has not been validated. To determine if true estimation of CBF could be obtained with Doppler TEE, seven mongrel dogs (weight range 28 kg-36 kg) were evaluated. Simultaneous CBF determinations by Doppler TEE and epicardial electromagnetic flow (EMF) and/or epicardial Doppler flow (EDF) probes were compared. Measurements were obtained at baseline and following varying degrees of proximal coronary occlusion, which produced reactive hyperemia. RESULTS: Consistent Doppler flow waveforms were obtainable by Doppler TEE in 34 different measurements during perturbations: Mean for TEE Flow (ml/min) = 85, EMF or EDF Flow (ml/min) = 53; Standard Deviation for TEE Flow (ml/min) = 45, EMF or EDF Flow (ml/min) = 38; Minimum for TEE Flow (ml/min) = 42, EMF or EDF Flow (ml/min) = 11; and Maximum for TEE Flow (ml/min) = 174, EMF or EDF Flow (ml/min) = 130. TEE Flow (ml/min) = 1.1 EMF/EDF flow + 26.3. There was a general trend towards overestimation of CBF by Doppler TEE. This study demonstrates that Doppler TEE is a promising method for obtaining measurements of CBF over the physiologic range.
Asunto(s)
Circulación Coronaria/fisiología , Vasos Coronarios/diagnóstico por imagen , Ecocardiografía Transesofágica/métodos , Animales , Velocidad del Flujo Sanguíneo , Intervalos de Confianza , Perros , Modelos Lineales , Modelos Animales , Probabilidad , Valores de Referencia , Sensibilidad y Especificidad , Ultrasonografía Doppler/métodosRESUMEN
The system N transporter SN1 has been proposed to mediate the efflux of glutamine from cells required to sustain the urea cycle and the glutamine-glutamate cycle that regenerates glutamate and gamma-aminobutyric acid (GABA) for synaptic release. We now show that SN1 also mediates an ionic conductance activated by glutamine, and this conductance is selective for H(+). Although SN1 couples amino acid uptake to H(+) exchange, the glutamine-gated H(+) conductance is not stoichiometrically coupled to transport. Protons thus permeate SN1 both coupled to and uncoupled from amino acid flux, providing novel mechanisms to regulate the transfer of glutamine between cells.
Asunto(s)
Sistemas de Transporte de Aminoácidos/metabolismo , Animales , Astrocitos/metabolismo , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Activación del Canal Iónico , Protones , Xenopus , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Left ventricular function is one of the most important determinates of long-term prognosis in patients with coronary artery disease. In recent years, it has become apparent that left ventricular dysfunction in patients with coronary artery disease is not always an irreversible process stemming from myocardial necrosis and fibrosis. Myocardial tissue can undergo both a state of potential reversible dysfunction because of prolonged sustained ischemia (hibernating myocardium) or episodes of acute ischemia (stunned myocardium). Revascularization of this tissue may improve regional and global left ventricular function and therefore prognosis. Numerous studies have now firmly established dobutamine echocardiography as a safe, reliable, and accurate imaging modality in the assessment of reversible left ventricular dysfunction. Furthermore, dobutamine echocardiography has been shown to have good sensitivity, specificity, and, more importantly, positive predictive accuracy in identifying both acute and chronic reversible left ventricular dysfunction for risk satisfaction and prognosis.
Asunto(s)
Aturdimiento Miocárdico/diagnóstico por imagen , Disfunción Ventricular Izquierda/diagnóstico por imagen , Cardiotónicos , Dipiridamol , Dobutamina , Ecocardiografía/métodos , Prueba de Esfuerzo , Humanos , Nitroglicerina , Pronóstico , Medición de Riesgo , Vasodilatadores , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
OBJECTIVES: We evaluated a novel protocol of dual-isotope, gated single-photon emission computed tomographic (SPECT) imaging combined with low and high dose dobutamine as a single test for the characterization of various types of altered myocardial dysfunction. BACKGROUND: Myocardial perfusion tomography and echocardiography have been used separately for the assessment of myocardial viability. However, it is possible to assess perfusion, function and contractile reserve using gated SPECT imaging. METHODS: We studied 54 patients with ischemic cardiomyopathy using rest and 4 h redistribution thallium-201 imaging and dobutamine technetium-99m sestamibi SPECT imaging. The sestamibi images were acquired 1 h after infusion of the maximal tolerated dose of dobutamine and again during infusion of dobutamine at a low dose to estimate contractile reserve. Myocardial segments were defined as hibernating, stunned, remodeled or scarred. RESULTS: Severe regional dysfunction was present in 584 (54%) of 1,080 segments. Based on the combination of function and perfusion characteristics in these 584 segments, 24% (n = 140) were labeled as hibernating; 23% (n = 136) as stunned; 30% (n = 177) as remodeled; and 22% (n = 131) as scarred. Contractile reserve, represented by improvement in wall motion/thickening by low dose dobutamine, was observed in 83% of stunned, 59% of hibernating, 35% of remodeled and 13% of scarred myocardial segments (p<0.05). CONCLUSIONS: It is possible with this new imaging technique to characterize dysfunctional myocardium as stunned, hibernating, remodeled and nonviable. These subtypes often coexist in the same patient.
Asunto(s)
Isquemia Miocárdica/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , Anciano , Cardiotónicos/administración & dosificación , Dobutamina/administración & dosificación , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aturdimiento Miocárdico/diagnóstico por imagenRESUMEN
The extent and degree of myocardial viability is an important parameter in the risk stratification of patients with significant left ventricular dysfunction due to coronary artery disease (CAD). Although several imaging modalities can identify viable myocardium, dobutamine stress echocardiography has gained considerable importance as an accurate, safe, and reliable method. In patients with significant left ventricular dysfunction secondary to CAD, identifying the presence and extent of contractile reserve and, therefore, viable myocardium, during low dose dobutamine infusion can predict recovery of left ventricular function postrevascularization, survival, and future cardiac events.
Asunto(s)
Ecocardiografía/métodos , Contracción Miocárdica/fisiología , Isquemia Miocárdica/diagnóstico por imagen , Cardiotónicos/administración & dosificación , Dobutamina/administración & dosificación , Prueba de Esfuerzo , Humanos , Infusiones Intravenosas , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/fisiopatología , Pronóstico , Reproducibilidad de los Resultados , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
The diagnostic accuracy of dobutamine stress echocardiography is limited in patients with poor transthoracic acoustic windows. Transesophageal echocardiography (TEE) overcomes these limitations and thus may increase the clinical usefulness of dobutamine stress echocardiography. The present study was designed to compare the diagnostic accuracies of transesophageal and transthoracic dobutamine stress echocardiography for the identification of coronary artery disease (CAD) in a cohort of patients with a higher incidence of poor acoustic windows. Forty-two male patients (mean age, 66 +/- 9 years) underwent dobutamine stress echocardiography with simultaneous transesophageal and transthoracic imaging. Coronary arteriography was performed in 28 patients (67%). Transesophageal imaging adequately visualized 99.6% of left ventricular segments compared with 76.2% visualized by transthoracic imaging (P < 0.0001). There was substantial agreement between the two techniques for segmental wall motion analysis at baseline (kappa 0.76; 95% CI, 0.70-0.82); however, at peak dobutamine dose, agreement was significantly reduced (kappa 0.62; 95% CI, 0.55-0.69). The sensitivity (88% vs 75%), specificity (100% vs 75%), and positive predictive value (100% vs 80%) for the identification of CAD were all superior for transesophageal imaging. Transesophageal imaging correctly identified 11 of the 12 patients (92%) with multivessel disease compared with 5 patients (42%) identified by transthoracic imaging (P < 0.03). There were no major complications. Transesophageal dobutamine stress echocardiography is a safe, feasible, and accurate technique for the identification and risk stratification of patients with CAD. Transesophageal imaging appears to be superior to transthoracic imaging for identifying both the presence and extent of CAD, specifically in patients with poor acoustic windows.
Asunto(s)
Dobutamina , Ecocardiografía Transesofágica , Ecocardiografía , Isquemia Miocárdica/diagnóstico por imagen , Simpatomiméticos , Anciano , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Humanos , Masculino , Valor Predictivo de las Pruebas , Medición de Riesgo , Sensibilidad y EspecificidadRESUMEN
The extent and degree of myocardial viability are important parameters in the risk stratification of patients with significant left ventricular dysfunction secondary to coronary artery disease. Although several imaging modalities can identify viable myocardium, dobutamine stress echocardiography has gained considerable importance as an accurate, safe, and reliable method. In patients with significant left ventricular dysfunction secondary to coronary artery disease, identification of the presence and extent of contractile reserve and, therefore, viable myocardium during low-dose dobutamine infusion can predict the recovery of left ventricular function after revascularization, survival rate, and future cardiac events.
Asunto(s)
Ecocardiografía , Disfunción Ventricular Izquierda/diagnóstico por imagen , Medios de Contraste , Dipiridamol , Dobutamina , Humanos , Nitroglicerina , PronósticoRESUMEN
Exercise and pharmacological stress echocardiography are well-accepted techniques of evaluating coronary artery disease in adults. In children, however, experience with stress echocardiography is limited and continues to evolve. The objective of this focused review was to describe the experience with exercise and dobutamine stress echocardiography in the pediatric population, with an emphasis on technique, current indications, and future directions. Experience is reported in children with prior Kawasaki disease or heart transplant recipients, as well as patients with congenital coronary abnormalities. In addition, stress echocardiography has been used in patients who have undergone coronary artery bypass graft surgery to evaluate short- and long-term graft patterning. Stress echocardiography appears to be a feasible, safe, and useful modality for the noninvasive assessment of flow-limiting stenosis in the pediatric population and can be used serially in the routine follow-up and risk stratification in children at risk for coronary events.
Asunto(s)
Dobutamina , Ecocardiografía , Prueba de Esfuerzo , Niño , Anomalías de los Vasos Coronarios/diagnóstico por imagen , Cardiopatías Congénitas/diagnóstico por imagen , Trasplante de Corazón , Humanos , Síndrome Mucocutáneo Linfonodular/diagnóstico por imagenRESUMEN
The objective of this article was to determine whether the presence of left ventricular apical thrombus is a marker of nonviable myocardium. Reduced coronary blood flow secondary to atherosclerosis may result in chronic reversible left ventricular wall-motion abnormalities. Severe regional abnormalities also predispose to formation of left ventricular thrombus. The relationship between left ventricular apical thrombus and myocardial viability has not been previously described. Eighty patients with coronary artery disease and chronic left ventricular dysfunction were studied by dobutamine stress echocardiography. Left ventricular apical thrombus was identified using echocardiographic criteria. Wall-motion analysis was performed using a standard 16-segment model and ejection fraction was calculated. As a result, 48 patients (60%) had definite or highly suspicious findings for left ventricular thrombus (group 1), and 32 patients (40%) had no thrombus (group 2). Group 1 had significantly higher composite (54.0 +/- 5.8 vs 43.3 +/- 6.4) and apical (6.0 +/- 2.7 vs 12.4 +/- 3.4) wall-motion scores compared to those in group 2 (P = 0.01). Thirty-two patients (67%) in group 1 demonstrated no contractile reserve in the apical segments, consistent with lack of viability, versus eight patients (25%) in group 2 (P = 0.0003). The number of viable apical segments per patient was significantly less in group 1 (0.7 +/- 1.2) versus group 2 (1.8 +/- 1.3) (P = 0.01). Left ventricular apical thrombus is more likely to be present when there is absence of myocardial viability in the corresponding segments.
Asunto(s)
Ecocardiografía , Cardiopatías/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Disfunción Ventricular Izquierda/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Enfermedad Coronaria/complicaciones , Dobutamina , Prueba de Esfuerzo , Femenino , Cardiopatías/etiología , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Contracción Miocárdica , Probabilidad , Medición de Riesgo , Volumen Sistólico , Trombosis/etiología , Disfunción Ventricular Izquierda/etiologíaRESUMEN
Classical amino acid transport System A accounts for most of the Na(+)-dependent neutral amino acid uptake by mammalian cells. System A has also provided a paradigm for short- and long-term regulation by physiological stimuli. We now report the isolation of a cDNA encoding System A that shows close similarity to the recently identified System N transporter (SN1). The System A transporter (SA1) and SN1 share many functional characteristics, including a marked sensitivity to low pH, but, unlike SN1, SA1 does not mediate proton exchange. Transport mediated by SA1 is also electrogenic. Amino acid transport Systems A and N thus appear closely related in function as well as structure, but exhibit important differences in ionic coupling.
Asunto(s)
Sistemas de Transporte de Aminoácidos Neutros , Aminoácidos/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de Transporte de Membrana , Secuencia de Aminoácidos , Sistemas de Transporte de Aminoácidos , Animales , Transporte Biológico , Proteínas Portadoras/química , Electrofisiología , Biblioteca de Genes , Humanos , Hibridación in Situ , Potenciales de la Membrana , Modelos Moleculares , Datos de Secuencia Molecular , Protones , Ratas , Proteínas Recombinantes/metabolismo , Análisis de Secuencia de ADN , Sodio/metabolismo , Distribución Tisular , beta-Alanina/análogos & derivados , beta-Alanina/metabolismoRESUMEN
Protein phosphatase inhibitor-1 (I-1) has been proposed as a regulatory element in the signal transduction cascade that couples postsynaptic calcium influx to long-term changes in synaptic strength. We have evaluated this model using mice lacking I-1. Recordings made in slices prepared from mutant animals and also in anesthetized mutant animals indicated that long-term potentiation (LTP) is deficient at perforant path-dentate granule cell synapses. In vitro, this deficit was restricted to synapses of the lateral perforant path. LTP at Schaffer collateral-CA1 pyramidal cell synapses remained normal. Thus, protein phosphatase-1-mediated regulation of NMDA receptor-dependent synaptic plasticity involves heterogeneous molecular mechanisms, in both different dendritic subregions and different neuronal subtypes. Examination of the performance of I-1 mutants in spatial learning tests indicated that intact LTP at lateral perforant path-granule cell synapses is either redundant or is not involved in this form of learning.
Asunto(s)
Proteínas Portadoras , Péptidos y Proteínas de Señalización Intracelular , Potenciación a Largo Plazo/genética , Plasticidad Neuronal/genética , Fosfoproteínas Fosfatasas/metabolismo , Proteínas de Unión al ARN/genética , Animales , Giro Dentado/citología , Giro Dentado/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Femenino , Expresión Génica/fisiología , Masculino , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Vía Perforante/citología , Fosfoproteínas/metabolismo , Proteína Fosfatasa 1 , Células Piramidales/química , Células Piramidales/enzimología , Proteínas de Unión al ARN/análisis , Proteínas de Unión al ARN/metabolismo , Percepción Espacial/fisiología , Sinapsis/química , Sinapsis/enzimología , AguaRESUMEN
OBJECTIVES: This study was performed to assess the prognostic implications of myocardial contractile reserve (MCR) in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. BACKGROUND: MCR during dobutamine stress echocardiography (DSE) identifies viable myocardium that may improve in function after revascularization. Whether revascularization influences prognosis of patients with MCR has not been determined. METHODS: We performed DSE in 80 patients with CAD and LV dysfunction (ejection fraction < or =40%). Viable myocardium was defined in dysfunctional myocardial segments as enhanced thickening and contraction during low-dose dobutamine (5 to 10 mcg/kg/min). Serial prospective follow-up was obtained in all patients (mean follow-up 2.2 +/- 1.1 years). RESULTS: Among 52 patients treated medically, there were 20 cardiac deaths. By multivariate analysis, the number of dysfunctional segments demonstrating MCR was the strongest predictor of survival (p < 0.03). Patients with MCR had better initial survival during medical therapy than did those without MCR, but this survival advantage was not maintained beyond three years. In contrast, survival was excellent in patients with MCR who underwent myocardial revascularization. Among 58 patients with MCR in > or =5 myocardial segments, survival at three years was 93 +/- 6% in the 24 patients who were revascularized but only 49 +/- 15% in the 34 treated medically (p < 0.02). CONCLUSIONS: Myocardial contractile reserve is a significant predictor of survival in patients with CAD and LV dysfunction undergoing medical therapy. Although patients with MCR have an initial survival advantage, this advantage is lost over the course of three years. In contrast, survival in patients with significant MCR is enhanced by revascularization.
Asunto(s)
Enfermedad Coronaria/fisiopatología , Contracción Miocárdica/fisiología , Disfunción Ventricular Izquierda/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Cardiotónicos/administración & dosificación , Enfermedad Crónica , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/terapia , Dobutamina/administración & dosificación , Ecocardiografía/métodos , Ecocardiografía/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/terapiaRESUMEN
Both dobutamine stress echocardiography (DSE) and myocardial perfusion scintigraphy are used to assess myocardial viability. Few studies have compared the data on myocardial viability and ischemia by low and peak dose DSE and myocardial perfusion imaging in the same patients. Fifty-four patients (45 men and 9 women aged 65 +/- 9 years) with ischemic cardiomyopathy (mean ejection fraction 24 +/- 9%) underwent rest 4-hour redistribution thallium-201 single-photon emission computed tomography (SPECT), low and peak dose DSE, and dobutamine sestamibi SPECT. A total of 864 segments were analyzed (16 segments/patient). Wall motion abnormality was present in 796 segments (92%), and contractile reserve during dobutamine infusion was seen in 400 of these segments (50%). Contractile reserve was seen in 331 of 509 hypokinetic segments (65%) and 69 of 287 akinetic/dyskinetic segments (24%) (p <0.001). Contractile reserve was more frequent in segments with normal thallium uptake (64%), reversible thallium defects (42%), or mild to moderate fixed thallium defects (48%) than severely fixed defects (22%) (p <0.05 each). Concordant information about viability by thallium imaging and DSE was obtained in 62% of segments. Dobutamine sestamibi ischemia was seen in 518 of 796 segments (65%) compared with 265 segments (33%) by DSE (p <0.001). Scintigraphic ischemia was noted in 126 of 195 segments (65%) demonstrating biphasic response, 129 of 205 segments (63%) showing sustained improvement, 42 of 70 segments (60%) deteriorating during dobutamine infusion, and 221 of 326 (68%) demonstrating no change (p = NS). Thus, in patients with ischemic cardiomyopathy, contractile reserve is more frequent in hypokinetic segments than akinetic/dyskinetic segments. The number of segments with normal or near-normal thallium uptake or with scintigraphic ischemia is significantly greater than the number of those capable of increasing contractile function or demonstrating an ischemic response during dobutamine echocardiography.