RESUMEN
PURPOSE: Patients undergoing mitral valve surgery are at risk for right ventricular (RV) dysfunction resulting from increased left atrial pressure and increased pulmonary artery impedance. Measures of longitudinal measures of RV function, such as displacement, are commonly performed but have been shown to be depressed after cardiac surgery despite good patient recovery. The aim of this observational study was to assess the early perioperative time course of longitudinal transthoracic echocardiographic (TTE) markers of RV function in a patient population undergoing mitral valve surgery. METHODS: Twenty patients undergoing mitral valve surgery were enrolled in this observational study. Right ventricular longitudinal measurements (tricuspid annular plane systolic excursion [TAPSE], strain, annular velocity [S'], and isovolumic acceleration [IVA]) were performed using TTE and colour Doppler imaging preoperatively (day 1) and postoperatively (days 2 and 6). Comparisons were made between the preoperative and postoperative measurements. RESULTS: Adequate echocardiographic imaging was obtained for all 20 patients. The TAPSE, strain, and S' measures remained depressed for up to one week (i.e., day 6) after surgery compared to preoperative values. The IVA was depressed on the first postoperative day (P > 0.001), but by day 6 it was no different from the preoperative value (P = 0.37). The median [interquartile range] time to discharge from hospital was 7 [6-9] days. CONCLUSION: Persistent, significant depression of longitudinal markers of RV function despite functional improvement (discharge from hospital) make it difficult to assess recovery during the early perioperative period. Isovolumic acceleration, a load-independent measure of contractility, might be a more reliable measure of early recovery in RV function in this patient population.
Asunto(s)
Válvula Mitral/cirugía , Función Ventricular Derecha/fisiología , Procedimientos Quirúrgicos Cardíacos , Ecocardiografía , Ecocardiografía Doppler , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Factores de Tiempo , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/fisiologíaRESUMEN
Pulmonary hypertension and associated vascular changes may frequently accompany left-sided heart disease in the adult cardiac surgical population. Perioperative assessment of right ventricular function using echocardiography is well established. In general, understanding the constraints upon which the right ventricle must work is mostly limited to invasive monitoring consisting of pulmonary artery pressures, cardiac output, and pulmonary vascular resistance. The latter 2 measurements assume constant (mean) flows and pressures. The systolic and diastolic pressures offer a limited understanding of the pulsatile constraints, which may become significant in disease. In normal physiology, pressure and flow waves display near-similar contours. When left atrial pressure and pulmonary vascular resistance are increased, changes in pulmonary arterial compliance will result in elevated impedance to right ventricular ejection. Pressure reflections, the result of strong reflectors, return more quickly in a noncompliant system. They augment pulmonary artery pressure causing a premature reduction in flow. As a result, pressure and flow waves will now be dissimilar. The impact of vascular changes on right ventricular ejection can be assessed using pulmonary artery Doppler spectral imaging. The normal flow velocity profile is rounded at its peak. Earlier peaks and premature reductions in flow will make it appear more triangular. In some cases, the flow pattern may appear notched. The measurement of acceleration time, the time from onset to peak flow velocity is an indicator of constraint to ejection; shortened times have been associated with increased pulmonary vascular resistance and pressure. Understanding the changes in the pulmonary arterial system in disease and the physics of the hemodynamic alterations are essential in interpreting pulmonary artery Doppler data. Analyzing pulmonary artery Doppler flow signals may assist in the evaluation of right ventricular function in patients with pulmonary vascular disease.
Asunto(s)
Hipertensión Pulmonar/diagnóstico por imagen , Atención Perioperativa/métodos , Circulación Pulmonar , Resistencia Vascular , Velocidad del Flujo Sanguíneo/fisiología , Ecocardiografía Doppler/métodos , Impedancia Eléctrica , Humanos , Hipertensión Pulmonar/fisiopatología , Circulación Pulmonar/fisiología , Resistencia Vascular/fisiologíaRESUMEN
OBJECTIVES: To examine the potential for using pulmonary Doppler to assess the hydraulic forces opposing right ventricular ejection in a perioperative setting. DESIGN: A prospective, observational study. SETTING: A university hospital tertiary-care center. PARTICIPANTS: Participants included 74 patients: 62 undergoing coronary artery bypass grafting and 12 undergoing mitral valve surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After induction of anesthesia, a pulmonary artery catheter was used to assess pulmonary artery pressures, cardiac output, and pulmonary vascular resistance. Transesophageal echocardiography was performed to measure pulsed-wave Doppler-derived acceleration time (AT) in 3 locations: the right ventricular outflow tract, the main pulmonary artery, and the right pulmonary artery. Flow reversal was observed in the main pulmonary artery in 96% of patients and possibly was responsible for the shorter ATs seen in this location. The best correlations between AT and pulmonary hemodynamic parameters were found in the right pulmonary artery. The relationships were strengthened in a subgroup of patients with elevated pulmonary capillary wedge pressure (PCWP). An acceleration time of 90 ms was associated with elevated pulmonary artery pressure and pulmonary vascular resistance. CONCLUSIONS: Flow reversal occurred frequently in the main pulmonary artery. AT in the right pulmonary artery yielded the best correlation with invasive hemodynamic parameters that were strengthened in patients with elevated PCWP. The addition of a PCWP measurement improved the reliability of AT in this patient population.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos/métodos , Cateterismo de Swan-Ganz/métodos , Ecocardiografía Doppler de Pulso/métodos , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiología , Presión Esfenoidal Pulmonar/fisiología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de TiempoRESUMEN
We previously reported that chick anterolateral endoderm (AL endoderm) induces cardiomyogenesis in mouse embryoid bodies. However, the requirement to micro-dissect AL endoderm from gastrulation-stage embryos precludes its use to identify novel cardiomyogenic factors, or to scale up cardiomyocyte numbers for therapeutic experiments. To circumvent this problem we have addressed whether human definitive endoderm (hDE) cells, which can be efficiently generated in large numbers from human embryonic stem cells (hESCs), can mimic the ability of AL endoderm to induce cardiac myogenesis. Results demonstrate that both hDE cells and medium conditioned by them induce cardiac myogenesis in pluripotent hESCs, as indicated by rhythmic beating and immunohistochemical/quantitative polymerase chain reaction monitoring of marker gene expression. The cardiomyogenic effect of hDE is enhanced when pluripotent hESCs are preinduced to the mes-endoderm state. Because this approach is tractable and scalable, it may facilitate identification of novel hDE-secreted factors for inclusion in defined cardiomyogenic cocktails.
Asunto(s)
Células Madre Embrionarias/citología , Endodermo/citología , Corazón/embriología , Miocardio/citología , Medicina Regenerativa/métodos , Perfilación de la Expresión Génica , Corazón/crecimiento & desarrollo , Humanos , Contracción Miocárdica , Células Madre PluripotentesRESUMEN
The formation of adenosine dampens inflammation by inhibiting most cells of the immune system. Among its actions on neutrophils, adenosine suppresses superoxide generation and regulates chemotactic activity. To date, most evidence implicates the G(s) protein-coupled A(2A) adenosine receptor (AR) as the primary AR subtype responsible for mediating the actions of adenosine on neutrophils by stimulating cAMP production. Given that the A(2B)AR is now known to be expressed in neutrophils and that it is a G(s) protein-coupled receptor, we examined in this study whether it signals to suppress neutrophil activities by using 2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide (BAY 60-6583), a new agonist for the human A(2B)AR that was confirmed in preliminary studies to be a potent and highly selective agonist for the murine A(2B)AR. We found that treating mouse neutrophils with low concentrations (10(-9) and 10(-8) M) of BAY 60-6583 inhibited formylated-methionine-leucine-phenylalanine (fMLP)-stimulated superoxide production by either naive neutrophils, tumor necrosis factor-α-primed neutrophils, or neutrophils isolated from mice treated systemically with lipopolysaccharide. This inhibitory action of BAY 60-6583 was confirmed to involve the A(2B)AR in experiments using neutrophils obtained from A(2B)AR gene knockout mice. It is noteworthy that BAY 60-6583 increased fMLP-stimulated superoxide production at higher concentrations (>1 µM), which was attributed to an AR-independent effect. In a standard Boyden chamber migration assay, BAY 60-6583 alone did not stimulate neutrophil chemotaxis or influence chemotaxis in response to fMLP. These results indicate that the A(2B)AR signals to suppress oxidase activity by murine neutrophils, supporting the idea that this low-affinity receptor for adenosine participates along with the A(2A)AR in regulating the proinflammatory actions of neutrophils.
Asunto(s)
Neutrófilos/metabolismo , Receptor de Adenosina A2B/metabolismo , Superóxidos/metabolismo , Agonistas del Receptor de Adenosina A2/farmacología , Antagonistas del Receptor de Adenosina A2/farmacología , Animales , Células de la Médula Ósea/metabolismo , Movimiento Celular/efectos de los fármacos , Quimiotaxis de Leucocito/efectos de los fármacos , AMP Cíclico/metabolismo , Células HEK293 , Humanos , Cinética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , N-Formilmetionina Leucil-Fenilalanina/antagonistas & inhibidores , N-Formilmetionina Leucil-Fenilalanina/farmacología , Neutrófilos/efectos de los fármacos , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Ensayo de Unión Radioligante , Receptor de Adenosina A2B/efectos de los fármacos , Receptor de Adenosina A2B/genéticaRESUMEN
Several recent studies have demonstrated that the transplantation of pluripotent murine embryonic stem cells (mESCs) can improve or restore the function of infarcted myocardium. Although the extent of remuscularization and its contribution to the restoration of function are unclear, these outcomes are likely strongly influenced by factors in the infarcted and/or ischemic environment. As an initial step toward understanding how the ischemic environment of host myocardium affects transplanted pluripotent cells, we have taken a reductionist approach wherein mESCs are cultured in medium containing ischemic myocardial interstitial fluid (iMIF). iMIF is generated in canine myocardium during eight hourly episodes of transient ischemia and collected on a daily basis, over a 24-day collection period. iMIF strongly reduced the numbers of pluripotent mESCs after 11 days in culture. This inhibitory effect, which was most pronounced for iMIF pools from early time points of the 24-day collection period, resulted from an inhibition of cell proliferation. iMIF also inhibited the differentiation of pluripotent mESCs into cardiomyocytes. By contrast, the expression of vascular smooth muscle and endothelial cell markers was relatively unaffected, consistent with previous findings that iMIF promotes angiogenesis. Taken together, these results suggest that whereas the ischemic/infarcted environment is favorable to stem cell-mediated angiogenesis, it is hostile to cardiac myogenesis. These findings also imply that observations of mESC-mediated improvement of cardiac function after transplantation of pluripotent cells do not reflect remuscularization.
Asunto(s)
Diferenciación Celular , Proliferación Celular , Células Madre Embrionarias/metabolismo , Líquido Extracelular/metabolismo , Células Madre Mesenquimatosas/metabolismo , Isquemia Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Células Madre Pluripotentes/metabolismo , Animales , Biomarcadores/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Perros , Regulación hacia Abajo , Células Madre Embrionarias/patología , Células Endoteliales/metabolismo , Células Madre Mesenquimatosas/patología , Ratones , Músculo Liso Vascular/metabolismo , Isquemia Miocárdica/patología , Miocitos Cardíacos/patología , Células Madre Pluripotentes/patología , Suero/metabolismo , Factores de TiempoRESUMEN
Because pluripotent embryonic stem cells (ESCs) are able to differentiate into any tissue, they are attractive agents for tissue regeneration. Although improvement of cardiac function has been observed after transplantation of pluripotent ESCs, the extent to which these effects reflect ESC-mediated remuscularization, revascularization, or paracrine mechanisms is unknown. Moreover, because ESCs may generate teratomas, the ability to predict the outcome of cellular differentiation, especially when transplanting pluripotent ESCs, is essential; conversely, a requirement to use predifferentiated ESCs would limit their application to highly characterized subsets that are available in limited numbers. In the experiments reported here, we transplanted low numbers of two murine ESC lines, respectively engineered to express a beta-galactosidase gene from either a constitutive (elongation factor) or a cardiac-specific (alpha-myosin heavy chain) promoter, into infarcted mouse myocardium. Although ESC-derived tumors formed within the pericardial space in 21% of injected hearts, lacZ histochemistry revealed that engraftment of ESC was restricted to the ischemic myocardium. Echocardiographic monitoring of ESC-injected hearts that did not form tumors revealed functional improvements by 4 weeks postinfarction, including significant increases in ejection fraction, circumferential fiber shortening velocity, and peak mitral blood flow velocity. These experiments indicate that the infarcted myocardial environment can support engraftment and cardiomyogenic differentiation of pluripotent ESCs, concomitant with partial functional recovery.
Asunto(s)
Células Madre Embrionarias/trasplante , Infarto del Miocardio/terapia , Células Madre Pluripotentes/trasplante , Regeneración , Animales , Miosinas Cardíacas/genética , Diferenciación Celular , Línea Celular , Proliferación Celular , Supervivencia Celular , Circulación Coronaria , Modelos Animales de Enfermedad , Ecocardiografía Doppler , Células Madre Embrionarias/metabolismo , Genes Reporteros , Neoplasias Cardíacas/etiología , Neoplasias Cardíacas/patología , Operón Lac , Masculino , Ratones , Ratones Endogámicos C57BL , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Miocardio/patología , Cadenas Pesadas de Miosina/genética , Células Madre Pluripotentes/metabolismo , Regiones Promotoras Genéticas/genética , Coloración y Etiquetado/métodos , Trasplante de Células Madre/efectos adversos , Función Ventricular Izquierda , beta-Galactosidasa/genética , beta-Galactosidasa/metabolismoRESUMEN
This paper presents and proves an algorithm to calculate the isotopic composition of individual (nominal) isotopic peaks. From this information one can calculate the accurate masses of isotopic peaks. This opens the way to use accurate mass measurements to determine chemical compositions of compounds using non-mono-isotopic peaks. The algorithm is computationally efficient and rigorously correct in the absence of roundoff error. Highly effective error correction strategies are described to detect and correct computational errors arising in practical calculations. Results from theoretical calculations of isotopic masses for a krypton inclusion complex agreed well with experimental measurements.