Summary of the II Brazilian Guideline Update on Acute Heart Failure 2009/2011

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

Automatic algorithm for monitoring systolic pressure variation and difference in pulse pressure

BACKGROUND: Difference in pulse pressure (dPP) reliably predicts fluid responsiveness in patients. We have developed a respiratory variation (RV) monitoring device (RV monitor), which continuously records both airway pressure and arterial blood pressure (ABP). We compared the RV monitor measurements with manual dPP measurements. METHODS: ABP and airway pressure (PAW) from 24 patients were recorded. Data were fed to the RV monitor to calculate dPP and systolic pressure variation in two different ways: (a) considering both ABP and PAW (RV algorithm) and (b) ABP only (RV(slim) algorithm). Additionally, ABP and PAW were recorded intraoperatively in 10-min intervals for later calculation of dPP by manual assessment. Interobserver variability was determined. Manual dPP assessments were used for comparison with automated measurements. To estimate the importance of the PAW signal, RV(slim) measurements were compared with RV measurements. RESULTS: For the 24 patients, 174 measurements (6-10 per patient) were recorded. Six observers assessed dPP manually in the first 8 patients (10-min interval, 53 measurements); no interobserver variability occurred using a computer-assisted method. Bland-Altman analysis showed acceptable bias and limits of agreement of the 2 automated methods compared with the manual method (RV: -0.33% +/- 8.72% and RV(slim): -1.74% +/- 7.97%). The difference between RV measurements and RV(slim) measurements is small (bias -1.05%, limits of agreement 5.67%). CONCLUSIONS: Measurements of the automated device are comparable with measurements obtained by human observers, who use a computer-assisted method. The importance of the PAW signal is questionable.

Impact of epinephrine and norepinephrine on two dynamic indices in a porcine hemorrhagic shock model

Abstract BACKGROUND: Pulse pressure variations (PPVs) and stroke volume variations (SVVs) are dynamic indices for predicting fluid responsiveness in intensive care unit patients. These hemodynamic markers underscore Frank-Starling law by which volume expansion increases cardiac output (CO). The aim of the present study was to evaluate the impact of the administration of catecholamines on PPV, SVV, and inferior vena cava flow (IVCF). METHODS: In this prospective, physiologic, animal study, hemodynamic parameters were measured in deeply sedated and mechanically ventilated pigs. Systemic hemodynamic and pressure-volume loops obtained by inferior vena cava occlusion were recorded. Measurements were collected during two conditions, that is, normovolemia and hypovolemia, generated by blood removal to obtain a mean arterial pressure value lower than 60 mm Hg. At each condition, CO, IVCF, SVV, and PPV were assessed by catheters and flow meters. Data were compared between the conditions normovolemia and hypovolemia before and after intravenous administrations of norepinephrine and epinephrine using a nonparametric Wilcoxon test. RESULTS: Eight pigs were anesthetized, mechanically ventilated, and equipped. Both norepinephrine and epinephrine significantly increased IVCF and decreased PPV and SVV, regardless of volemic conditions (p < 0.05). However, epinephrine was also able to significantly increase CO regardless of volemic conditions. CONCLUSION: The present study demonstrates that intravenous administrations of norepinephrine and epinephrine increase IVCF, whatever the volemic conditions are. The concomitant decreases in PPV and SVV corroborate the fact that catecholamine administration recruits unstressed blood volume. In this regard, understanding a decrease in PPV and SVV values, after catecholamine administration, as an obvious indication of a restored volemia could be an outright misinterpretation.

Traitement de la maladie du greffon contre l’hôte chronique par la photophérèse extra corporelle au TH9402 : m écanisme de régulation de la maladie du greffon contre l’hôte chronique par les cellules T régulatrices

La maladie du greffon contre l’hôte (GVHD) est la principale cause de mortalité et de morbidité suite aux greffes de cellules souches hématopoïétiques. Plusieurs patients demeurent réfractaires aux traitements actuels ce qui rend nécessaire le développement de nouvelles stratégies afin de combattre cette maladie. Dans l’étude qui suit, nous avons utilisé un nouvel agent thérapeutique, le TH9402, une molécule photosensible et démontré qu’elle permet, lorsqu’exposée à la lumière visible (514 nm), d’éliminer sélectivement les cellules T activées in vivo tout en préservant les cellules T au repos et les cellules T régulatrices (Tregs). Les Tregs ainsi préservés peuvent abroger la réponse alloréactive par la sécrétion d’IL-10 ou par contact cellule-cellule via un mécanisme impliquant le CTLA-4. Nous avons découvert que la signalisation du CTLA-4 était associée à une hausse de la population Treg in vitro. Cette hausse est due à la conversion de cellules T CD4+CD25- en Tregs et non à une prolifération sélective des Tregs. Dans la deuxième partie de cette étude, nous avons démontré que la signalisation de CTLA-4 était associée à une augmentation de l’expression de la protéine Indoleamine 2,3 dioxygenase (IDO). Ces effets nécessitent la déplétion du tryptophane ainsi que de la protéine de phase aigue GCN2. Finalement, nous avons observé que l’infusion de cellules traitées au TH9402 chez des patients souffrant de GVHD chronique est associée à une augmentation de la population Treg chez ces patients sans causer de lymphopénie ni de diminution de la réponse immunitaire dirigée contre les antigènes viraux. Ces résultats suggèrent que le traitement au TH9402 pourrait représenter une approche particulièrement intéressante pour le traitement de la GVHD chronique réfractaire aux traitements actuels. De plus, l’augmentation de l’expression d’IDO pourrait être utilisée comme valeur prédictive de la réponse du patient au traitement. Ceci pourrait permettre d’améliorer la qualité de soins ainsi que de la qualité de vie des patients souffrant de GVHD chronique.

Traitement de la maladie du greffon contre l’hôte chronique par la photophérèse extra corporelle au TH9402 : m écanisme de régulation de la maladie du greffon contre l’hôte chronique par les cellules T régulatrices

La maladie du greffon contre l’hôte (GVHD) est la principale cause de mortalité et de morbidité suite aux greffes de cellules souches hématopoïétiques. Plusieurs patients demeurent réfractaires aux traitements actuels ce qui rend nécessaire le développement de nouvelles stratégies afin de combattre cette maladie. Dans l’étude qui suit, nous avons utilisé un nouvel agent thérapeutique, le TH9402, une molécule photosensible et démontré qu’elle permet, lorsqu’exposée à la lumière visible (514 nm), d’éliminer sélectivement les cellules T activées in vivo tout en préservant les cellules T au repos et les cellules T régulatrices (Tregs). Les Tregs ainsi préservés peuvent abroger la réponse alloréactive par la sécrétion d’IL-10 ou par contact cellule-cellule via un mécanisme impliquant le CTLA-4. Nous avons découvert que la signalisation du CTLA-4 était associée à une hausse de la population Treg in vitro. Cette hausse est due à la conversion de cellules T CD4+CD25- en Tregs et non à une prolifération sélective des Tregs. Dans la deuxième partie de cette étude, nous avons démontré que la signalisation de CTLA-4 était associée à une augmentation de l’expression de la protéine Indoleamine 2,3 dioxygenase (IDO). Ces effets nécessitent la déplétion du tryptophane ainsi que de la protéine de phase aigue GCN2. Finalement, nous avons observé que l’infusion de cellules traitées au TH9402 chez des patients souffrant de GVHD chronique est associée à une augmentation de la population Treg chez ces patients sans causer de lymphopénie ni de diminution de la réponse immunitaire dirigée contre les antigènes viraux. Ces résultats suggèrent que le traitement au TH9402 pourrait représenter une approche particulièrement intéressante pour le traitement de la GVHD chronique réfractaire aux traitements actuels. De plus, l’augmentation de l’expression d’IDO pourrait être utilisée comme valeur prédictive de la réponse du patient au traitement. Ceci pourrait permettre d’améliorer la qualité de soins ainsi que de la qualité de vie des patients souffrant de GVHD chronique.

Seguridad del monitoreo hemodinámico invasivo versus mínimamente invasivo en pacientes con choque cardiogénico en cuidado intensivo adultos. Revisión sistemática

Introducción: El monitoreo hemodinámico es una herramienta para diagnosticar el choque cardiogénico y monitorear la respuesta al tratamiento; puede ser invasivo, mínimamente invasivo o no invasivo. Se realiza rutinariamente con catéter de arteria pulmonar (CAP) o catéter de Swan Ganz; nuevas técnicas de monitoreo hemodinámico mínimamente invasivo tienen menor tasa de complicaciones. Actualmente se desconoce cuál técnica de monitoreo cuenta con mayor seguridad en el paciente con choque cardiogénico. Objetivo: Evaluar la seguridad del monitoreo hemodinámico invasivo comparado con el mínimamente invasivo en pacientes con choque cardiogénico en cuidado intensivo adultos. Diseño: Revisión sistemática de la literatura. Búsqueda en Pubmed, EMBASE, OVID - Cochrane Library, Lilacs, Scielo, registros de ensayos clínicos, actas de conferencias, repositorios, búsqueda de literatura gris en Google Scholar, Teseo y Open Grey hasta agosto de 2016, publicados en inglés y español. Resultados: Se identificó un único estudio con 331 pacientes críticamente enfermos que comparó el monitoreo hemodinámico con CAP versus PiCCO que concluyó que después de la corrección de los factores de confusión, la elección del tipo de monitoreo no influyó en los resultados clínicos más importantes en términos de complicaciones y mortalidad. Dado que se incluyeron otros diagnósticos, no es posible extrapolar los resultados sólo a choque cardiogénico. Conclusión: En la literatura disponible no hay evidencia de que el monitoreo hemodinámico invasivo comparado con el mínimamente invasivo, en pacientes adultos críticamente enfermos con choque cardiogénico, tenga diferencias en cuanto a complicaciones y mortalidad.

Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response.

RATIONALE: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a well-documented neurobiological finding in major depression. Moreover, clinically effective therapy with antidepressant drugs may normalize the HPA axis activity. OBJECTIVE: The aim of this study was to test whether citalopram (R/S-CIT) affects the function of the HPA axis in patients with major depression (DSM IV). METHODS: Twenty depressed patients (11 women and 9 men) were challenged with a combined dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH) stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16 weeks of 40 mg/day R/S-CIT treatment. RESULTS: The results show a time-dependent reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the DEX/CRH test both in treatment responders and nonresponders within 16 weeks. There was a significant relationship between post-DEX baseline cortisol levels (measured before administration of CRH) and severity of depression at pretreatment baseline. Multiple linear regression analyses were performed to identify the impact of psychopathology and hormonal stress responsiveness and R/S-CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of decrease in cortisol responsivity from pretreatment baseline to week 4 on drug [delta-area under the curve (AUC) cortisol] was a significant predictor (p<0.0001) of the degree of symptom improvement following 16 weeks on drug (i.e., decrease in HAM-D21 total score). The model demonstrated that the interaction of CSF S-CIT concentrations and clinical improvement was the most powerful predictor of AUC cortisol responsiveness. CONCLUSION: The present study shows that decreased AUC cortisol was highly associated with S-CIT concentrations in plasma and CSF. Therefore, our data suggest that the CSF or plasma S-CIT concentrations rather than the R/S-CIT dose should be considered as an indicator of the selective serotonergic reuptake inhibitors (SSRIs) effect on HPA axis responsiveness as measured by AUC cortisol response.

Dynamic arterial elastance to predict arterial pressure response to volume loading in preload-dependent patients

INTRODUCTION Hemodynamic resuscitation should be aimed at achieving not only adequate cardiac output but also sufficient mean arterial pressure (MAP) to guarantee adequate tissue perfusion pressure. Since the arterial pressure response to volume expansion (VE) depends on arterial tone, knowing whether a patient is preload-dependent provides only a partial solution to the problem. The objective of this study was to assess the ability of a functional evaluation of arterial tone by dynamic arterial elastance (Ea(dyn)), defined as the pulse pressure variation (PPV) to stroke volume variation (SVV) ratio, to predict the hemodynamic response in MAP to fluid administration in hypotensive, preload-dependent patients with acute circulatory failure. METHODS We performed a prospective clinical study in an adult medical/surgical intensive care unit in a tertiary care teaching hospital, including 25 patients with controlled mechanical ventilation who were monitored with the Vigileo(®) monitor, for whom the decision to give fluids was made because of the presence of acute circulatory failure, including arterial hypotension (MAP ≤65 mmHg or systolic arterial pressure <90 mmHg) and preserved preload responsiveness condition, defined as a SVV value ≥10%. RESULTS Before fluid infusion, Ea(dyn) was significantly different between MAP responders (MAP increase ≥15% after VE) and MAP nonresponders. VE-induced increases in MAP were strongly correlated with baseline Ea(dyn) (r(2) = 0.83; P < 0.0001). The only predictor of MAP increase was Ea(dyn) (area under the curve, 0.986 ± 0.02; 95% confidence interval (CI), 0.84-1). A baseline Ea(dyn) value >0.89 predicted a MAP increase after fluid administration with a sensitivity of 93.75% (95% CI, 69.8%-99.8%) and a specificity of 100% (95% CI, 66.4%-100%). CONCLUSIONS Functional assessment of arterial tone by Ea(dyn), measured as the PVV to SVV ratio, predicted arterial pressure response after volume loading in hypotensive, preload-dependent patients under controlled mechanical ventilation.

Using computational fluid dynamics to predict head losses in the auxiliary elements of a microirrigation sand filter

It is often assumed that total head losses in a sand filter are solely due to the filtration media and that there are analytical solutions, such as the Ergun equation, to compute them. However, total head losses are also due to auxiliary elements (inlet and outlet pipes and filter nozzles), which produce undesirable head losses because they increase energy requirements without contributing to the filtration process. In this study, ANSYS Fluent version 6.3, a commercial computational fluid dynamics (CFD) software program, was used to compute head losses in different parts of a sand filter. Six different numerical filter models of varying complexities were used to understand the hydraulic behavior of the several filter elements and their importance in total head losses. The simulation results show that 84.6% of these were caused by the sand bed and 15.4% were due to auxiliary elements (4.4% in the outlet and inlet pipes, and 11.0% in the perforated plate and nozzles). Simulation results with different models show the important role of the nozzles in the hydraulic behavior of the sand filter. The relationship between the passing area through the nozzles and the passing area through the perforated plate is an important design parameter for the reduction of total head losses. A reduced relationship caused by nozzle clogging would disproportionately increase the total head losses in the sand filter

Complex promoter and coding region β2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness

The human β2-adrenergic receptor gene has multiple single-nucleotide polymorphisms (SNPs), but the relevance of chromosomally phased SNPs (haplotypes) is not known. The phylogeny and the in vitro and in vivo consequences of variations in the 5′ upstream and ORF were delineated in a multiethnic reference population and an asthmatic cohort. Thirteen SNPs were found organized into 12 haplotypes out of the theoretically possible 8,192 combinations. Deep divergence in the distribution of some haplotypes was noted in Caucasian, African-American, Asian, and Hispanic-Latino ethnic groups with >20-fold differences among the frequencies of the four major haplotypes. The relevance of the five most common β2-adrenergic receptor haplotype pairs was determined in vivo by assessing the bronchodilator response to β agonist in asthmatics. Mean responses by haplotype pair varied by >2-fold, and response was significantly related to the haplotype pair (P = 0.007) but not to individual SNPs. Expression vectors representing two of the haplotypes differing at eight of the SNP loci and associated with divergent in vivo responsiveness to agonist were used to transfect HEK293 cells. β2-adrenergic receptor mRNA levels and receptor density in cells transfected with the haplotype associated with the greater physiologic response were ≈50% greater than those transfected with the lower response haplotype. The results indicate that the unique interactions of multiple SNPs within a haplotype ultimately can affect biologic and therapeutic phenotype and that individual SNPs may have poor predictive power as pharmacogenetic loci.

Two dimensional computational fluid dynamic models for waste stabilisation ponds

Traditional waste stabilisation pond (WSP) models encounter problems predicting pond performance because they cannot account for the influence of pond features, such as inlet structure or pond geometry, on fluid hydrodynamics. In this study, two dimensional (2-D) computational fluid dynamics (CFD) models were compared to experimental residence time distributions (RTD) from literature. In one of the-three geometries simulated, the 2-D CFD model successfully predicted the experimental RTD. However, flow patterns in the other two geometries were not well described due to the difficulty of representing the three dimensional (3-D) experimental inlet in the 2-D CFD model, and the sensitivity of the model results to the assumptions used to characterise the inlet. Neither a velocity similarity nor geometric similarity approach to inlet representation in 2-D gave results correlating with experimental data. However. it was shown that 2-D CFD models were not affected by changes in values of model parameters which are difficult to predict, particularly the turbulent inlet conditions. This work suggests that 2-D CFD models cannot be used a priori to give an adequate description of the hydrodynamic patterns in WSP. (C) 1998 Elsevier Science Ltd. All rights reserved.

Finite element modelling of dissipative structures for nonequilibrium chemical reactions in fluid-saturated porous media

We use the finite element method to model and predict the dissipative structures of chemical species for a nonequilibrium chemical reaction system in a fluid-saturated porous medium. In particular, we explore the conditions under which dissipative structures of the species may exist in the Brusselator type of nonequilibrium chemical reaction. Since this is the first time the finite element method and related strategies have been used to study the chemical instability problems in a fluid-saturated porous medium, it is essential to validate the method and strategies before they are put into application. For this purpose, we have rigorously derived the analytical solutions for dissipative structures of chemical species in a benchmark problem, which geometrically is a square. Comparison of the numerical solutions with the analytical ones demonstrates that the proposed numerical method and strategy are robust enough to solve chemical instability problems in a fluid-saturated porous medium. Finally, the related numerical results from two application examples indicate that both the regime and the magnitude of pore-fluid flow have significant effects on the nature of the dissipative structures that developed for a nonequilibrium chemical reaction system in a fluid-saturated porous medium. The motivation for this study is that self-organization under conditions of pore-fluid flow in a porous medium is a potential mechanism of the orebody formation and mineralization in the upper crust of the Earth. (C) 2000 Elsevier Science S.A. All rights reserved.

Effects of hot intrusions on pore-fluid flow and heat transfer in fluid-saturated rocks

We use the finite element method to solve coupled problems between pore-fluid flow and heat transfer in fluid-saturated porous rocks. In particular, we investigate the effects of both the hot pluton intrusion and topographically driven horizontal flow on the distributions of the pore-flow velocity and temperature in large-scale hydrothermal systems. Since general mineralization patterns are strongly dependent on distributions of both the pore-fluid velocity and temperature fields, the modern mineralization theory has been used to predict the general mineralization patterns in several realistic hydrothermal systems. The related numerical results have demonstrated that: (1) The existence of a hot intrusion can cause an increase in the maximum value of the pore-fluid velocity in the hydrothermal system. (2) The permeability of an intruded pluton is one of the sensitive parameters to control the pore-fluid flow, heat transfer and ore body formation in hydrothermal systems. (3) The maximum value of the pore-fluid velocity increases when the bottom temperature of the hydrothermal system is increased. (4) The topographically driven flow has significant effects on the pore-fluid flow, temperature distribution and precipitation pattern of minerals in hydrothermal systems. (5) The size of the computational domain may have some effects on the pore-fluid flow and heat transfer, indicating that the size of a hydrothermal system may affect the pore-fluid flow and heat transfer within the system. (C) 2003 Elsevier Science B.V. All rights reserved.

Thermal Characteristics of Polybia scutellaris Nests (Hymenoptera: Vespidae) Using Computational Fluid Dynamics: A Possible Adaptation to Tropical Climates

Polybia scutellaris constructs huge nests characterized by numerous spinal projections on the surface. We investigated the thermal characteristics of P scutellaris nests in order to determine whether their nest temperature is homeothermically maintained and whether the spines play a role in the thermoregulation of the nests. In order to examine these hypotheses, we measured the nest temperature in a active nest and in an abandoned nest. The temperature in the active nest was almost stable at 27 degrees C, whereas that of the abandoned nest varied with changes in the ambient temperature, suggesting that nest temperature was maintained by the thermogenesis of colony individuals. In order to predict the thermal properties of the spines, a numerical simulation was employed. To construct a 3D-model of a P scutellaris nest, the nest architecture was simplified into an outer envelope and the surface spines, for both of which the initial temperature was set at 27 degrees C. The physical properties of the simulated nest were regarded to be those of wood since the nest of this species is constructed from plant materials. When the model was exposed to cool air (12 degrees C), the temperature was lower in the models with more spines. On the other hand, when the nest was heated (42 degrees C), the temperature increase was smaller in models with more spines. It is suggested that the spines act as a heat radiator, not as an insulator, against the changes in ambient temperature.

Detection of Toxoplasma gondii soluble antigen, SAG-1(p30), antibody and immune complex in the cerebrospinal fluid of HIV positive or negative individuals

Active infection by T. gondii was evaluated by immunoassay for soluble SAG-1 (p30), the major surface antigen from T. gondii, specific antibodies and immune complexes in human cerebrospinal fluid (CSF) samples. A total of 263 samples of CSF were collected from hospitalized patients presenting neurological disorders and analyzed for antibodies to HIV. Patients were divided into two groups: HIV positive (n = 96) or HIV negative (n =167). The results of the assays showed that 45% of all samples were positive for soluble SAG-1. Toxoplasma Ag/Ab immune complexes were detected in 19% of the CSF samples and 62% were positive for T. gondii- specific IgG. A combination of these assays in the presence of clinical findings consistent with active Toxoplasma infection may predict the presence of toxoplasmic encephalitis. Moreover, detection of soluble SAG-1 in the CSF of these individuals appears consistent with active infection.