Acute lung injury secondary to hydrochloric acid instillation induces small airway hyperresponsiveness.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure characterized by altered lung mechanics and poor oxygenation. Bronchial hyperresponsiveness has been reported in ARDS survivors and animal models of acute lung injury. Whether this hyperreactivity occurs at the small airways or not is unknown. OBJECTIVE: To determine ex-vivo small airway reactivity in a rat model of acute lung injury (ALI) by hydrochloric acid (HCl) instillation. METHODS: Twelve anesthetized rats were connected to mechanical ventilation for 4-hour, and randomly allocated to either ALI group (HCl intratracheal instillation; n=6) or Sham (intratracheal instillation of 0.9% NaCl; n=6). Oxygenation was assessed by arterial blood gases. After euthanasia, tissue samples from the right lung were harvested for histologic analysis and wet-dry weight ratio assessment. Precision cut lung slice technique (100-200 µm diameter) was applied in the left lung to evaluate ex vivo small airway constriction in response to histamine and carbachol stimulation, using phase-contrast video microscopy. RESULTS: Rats from the ALI group exhibited hypoxemia, worse histologic lung injury, and increased lung wet-dry weight ratio as compared with the sham group. The bronchoconstrictor responsiveness was significantly higher in the ALI group, both for carbachol (maximal contraction of 84.5±2.5% versus 61.4±4.2% in the Sham group, P<0.05), and for histamine (maximal contraction of 78.6±5.3% versus 49.6±5.3% in the Sham group, P<0.05). CONCLUSION: In an animal model of acute lung injury secondary to HCL instillation, small airway hyperresponsiveness to carbachol and histamine is present. These results may provide further insight into the pathophysiology of ARDS.

Disfunción Diafragmática en Ventilación Mecánica: Evaluación e Implicancias Clínicas / Diaphragmatic Dysfunction in Mechanical Ventilation: Evaluation and Clinical Implications

La debilidad diafragmática es un problema relevante en pacientes admitidos a la unidad de cuidados intensivos (UCI). Su presencia ha sido asociada a mayor tiempo en ventilación mecánica, weaning dificultoso, mayor riesgo de readmisión hospitalaria y mayor mortalidad. Las causas de esta debilidad son múltiples incluyendo factores relacionados a la severidad de la enfermedad, las intervenciones en la UCI y el uso de ventilación mecánica, termino conocido como miotrauma. Se han propuesto cuatro diferentes mecanismos de miotrauma relacionados a la sobre asistencia ventilatoria, baja asistencia ventilatoria, ocurrencia de contracciones diafragmáticas excéntricas y efecto de la presión espiratoria al final de espiración. Una adecuada evaluación y monitoreo de la función diafragmática es, por lo tanto, un aspecto clave que debe ser realizado al lado de la cama del paciente. La prueba de referencia para medir la función del diafragma es la presión transdiafragmática calculada como la diferencia entre la presión gástrica y presión esofágica. Adicionalmente, otras técnicas disponibles para la evaluación de la función del diafragma corresponden a la ecografía y la medición de la actividad eléctrica. Desde un punto de vista clínico, basado en la evidencia sobre disfunción diafragmática en los pacientes ventilados mecánicamente, uno de los principales desafíos actuales es poder buscar estrategias ventilatorias que incorporen protección diafragmática mientras se mantiene una ventilación protectora pulmonar. En este sentido, favorecer un nivel de esfuerzo inspiratorio adecuado junto con optimizar la interacción entre el paciente y el ventilador constituyen los principales objetivos de una ventilación diafragmática protectora.

Diaphragm weakness is a relevant problem in patients admitted to the intensive care unit (ICU). Its presence has been associated with prolonged mechanical ventilation, difficult weaning, higher risk of hospital readmission, and higher mortality. The causes of this weakness are multiple, including factors related to the severity of the disease, ICU interventions and the use of mechanical ventilation, a term known as myotrauma. Four different mechanisms of myotrauma have been proposed: 1. Ventilator over-assistance; 2. Ventilator under-assistance: 3. Eccentric diaphragm contractions: and 4. Excessive end-expiratory shortening by high PEEP. An adequate evaluation and monitoring of diaphragmatic function is, therefore, a key aspect that must be performed at the patient's bedside. The gold standard for measuring diaphragm function is transdiaphragmatic pressure calculated as the difference between gastric pressure and esophageal pressure. Furthermore, other techniques available for the evaluation of diaphragm function correspond to ultrasound and the measurement of its electrical activity. From a clinical point of view, based on diaphragmatic dysfunction evidence in mechanically ventilated patients, the main current challenge consists in applying ventilatory strategies that incorporate diaphragmatic protection while maintaining lung protective ventilation. In this sense, favoring an adequate level of inspiratory effort together with optimizing the interaction between the patient and the ventilator are the main objectives of diaphragm protective ventilation.

Simple Wireless Impedance Pneumography System for Unobtrusive Sensing of Respiration.

This extended paper presents the development and implementation at a prototype level of a wireless, low-cost system for the measurement of the electrical bioimpedance of the chest with two channels using the AD5933 in a bipolar electrode configuration to measure impedance pneumography. The measurement device works for impedance measurements ranging from 1 Ω to 1800 Ω. Fifteen volunteers were measured with the prototype. We found that the left hemithorax has higher impedance compared to the right hemithorax, and the acquired signal presents the phases of the respiratory cycle with variations between 1 Ω, in normal breathing, to 6 Ω in maximum inhalation events. The system can measure the respiratory cycle variations simultaneously in both hemithorax with a mean error of -0.18 ± 1.42 BPM (breaths per minute) in the right hemithorax and -0.52 ± 1.31 BPM for the left hemithorax, constituting a useful device for the breathing rate calculation and possible screening applications.

Early rise in central venous pressure during a spontaneous breathing trial: A promising test to identify patients at high risk of weaning failure?

BACKGROUND: The spontaneous breathing trial (SBT) assesses the risk of weaning failure by evaluating some physiological responses to the massive venous return increase imposed by discontinuing positive pressure ventilation. This trial can be very demanding for some critically ill patients, inducing excessive physical and cardiovascular stress, including muscle fatigue, heart ischemia and eventually cardiac dysfunction. Extubation failure with emergency reintubation is a serious adverse consequence of a failed weaning process. Some data suggest that as many as 50% of patients that fail weaning do so because of cardiac dysfunction. Unfortunately, monitoring cardiovascular function at the time of the SBT is complex. The aim of our study was to explore if central venous pressure (CVP) changes were related to weaning failure after starting an SBT. We hypothesized that an early rise on CVP could signal a cardiac failure when handling a massive increase on venous return following a discontinuation of positive pressure ventilation. This CVP rise could identify a subset of patients at high risk for extubation failure. METHODS: Two-hundred and four mechanically ventilated patients in whom an SBT was decided were subjected to a monitoring protocol that included blinded assessment of CVP at baseline, and at 2 minutes after starting the trial (CVP-test). Weaning failure was defined as reintubation within 48-hours following extubation. Comparisons between two parametric or non-parametric variables were performed with student T test or Mann Whitney U test, respectively. A logistic multivariate regression was performed to determine the predictive value on extubation failure of usual clinical variables and CVP at 2-min after starting the SBT. RESULTS: One-hundred and sixty-five patients were extubated after the SBT, 11 of whom were reintubated within 48h. Absolute CVP values at 2-minutes, and the change from baseline (dCVP) were significantly higher in patients with extubation failure as compared to those successfully weaned. dCVP was an early predictor for reintubation (OR: 1.70 [1.31,2.19], p<0.001). CONCLUSIONS: An early rise in CVP after starting an SBT was associated with an increased risk of extubation failure. This might represent a warning signal not captured by usual SBT monitoring and could have relevant clinical implications.

Cardiovascular Action of Insulin in Health and Disease: Endothelial L-Arginine Transport and Cardiac Voltage-Dependent Potassium Channels.

Impairment of insulin signaling on diabetes mellitus has been related to cardiovascular dysfunction, heart failure, and sudden death. In human endothelium, cationic amino acid transporter 1 (hCAT-1) is related to the synthesis of nitric oxide (NO) and insulin has a vascular effect in endothelial cells through a signaling pathway that involves increases in hCAT-1 expression and L-arginine transport. This mechanism is disrupted in diabetes, a phenomenon potentiated by excessive accumulation of reactive oxygen species (ROS), which contribute to lower availability of NO and endothelial dysfunction. On the other hand, electrical remodeling in cardiomyocytes is considered a key factor in heart failure progression associated to diabetes mellitus. This generates a challenge to understand the specific role of insulin and the pathways involved in cardiac function. Studies on isolated mammalian cardiomyocytes have shown prolongated action potential in ventricular repolarization phase that produces a long QT interval, which is well explained by attenuation in the repolarizing potassium currents in cardiac ventricles. Impaired insulin signaling causes specific changes in these currents, such a decrease amplitude of the transient outward K(+) (Ito) and the ultra-rapid delayed rectifier (IKur) currents where, together, a reduction of mRNA and protein expression levels of α-subunits (Ito, fast; Kv 4.2 and IKs; Kv 1.5) or ß-subunits (KChIP2 and MiRP) of K(+) channels involved in these currents in a MAPK mediated pathway process have been described. These results support the hypothesis that lack of insulin signaling can produce an abnormal repolarization in cardiomyocytes. Furthermore, the arrhythmogenic potential due to reduced Ito current can contribute to an increase in the incidence of sudden death in heart failure. This review aims to show, based on pathophysiological models, the regulatory function that would have insulin in vascular system and in cardiac electrophysiology.