RESUMEN
The COVID-19 pandemic has imposed substantial burdens on clinicians and there is a need to better understand the impact on mental health and well-being. This scoping review investigates the prevalence of mental health concerns in anaesthetists, risk and protective factors for mental well-being, and anaesthetists' pandemic-related concerns and support. We searched online databases for articles published between January 2020 and May 2022, using search terms related to: anaesthesia; burnout, well-being, mental health or stress; and COVID-19. We identified 20 articles comprising 19 different populations of anaesthetists (n = 8680) from 14 countries. Studies identified the prevalence of the following condition in anaesthetists: burnout (14-59%); stress (50-71%); anxiety (11-74%); depression (12-67%); post-traumatic stress (17-25%); psychological distress (52%); and insomnia (17-61%). Significant risk factors for poorer mental health included: direct COVID-19-related issues (fear of self and family exposure to infection; requirement for quarantine); practitioner health factors (insomnia; comorbidities); psychosocial factors (loneliness; isolation; perceived lack of support at home and work); demographic factors (female gender; non-white ethnicity; LGBTQIA+); and workplace factors (redeployment outside area of clinical practice; increased work effort; personal protective equipment shortages). Protective factors identified included: job satisfaction; perceived organisational justice; older age; and male sex. Anaesthetists' self-reported concerns related to: personal protective equipment; resource allocation; fear of infection; fear of financial loss; increased workload; and effective communication of protocols for patient treatment. Support from family, colleagues and hospital management was identified as an important coping mechanism. Findings from this review may support the design of interventions to enhance anaesthetists' psychological health during pandemic conditions and beyond. Future research should include consistent psychological outcome measures and rigorous experimental design beyond cross-sectional studies.
Asunto(s)
Agotamiento Profesional , COVID-19 , Trastornos del Inicio y del Mantenimiento del Sueño , Masculino , Femenino , Humanos , COVID-19/epidemiología , Salud Mental , Pandemias , SARS-CoV-2 , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Estudios Transversales , Depresión/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Agotamiento Profesional/epidemiología , AnestesistasRESUMEN
Background: Anaesthetists monitor auditory information about a patient's vital signs in an environment that can be noisy and while performing other cognitively demanding tasks. It can be difficult to identify oxygen saturation (SpO2) values using existing pulse oximeter auditory displays (sonifications). Methods: In a laboratory setting, we compared the ability of non-clinician participants to detect transitions into and out of an SpO2 target range using five different sonifications while they performed a secondary distractor arithmetic task in the presence of background noise. The control sonification was based on the auditory display of current pulse oximeters and comprised a variable pitch with an alarm. The four experimental conditions included an Alarm Only condition, a Variable pitch only condition, and two conditions using sonifications enhanced with additional sound dimensions. Accuracy to detect SpO2 target transitions was the primary outcome. Results: We found that participants using the two sonifications enhanced with the additional sound dimensions of tremolo and brightness were significantly more accurate (83 and 96%, respectively) at detecting transitions to and from a target SpO2 range than participants using a pitch only sonification plus alarms (57%) as implemented in current pulse oximeters. Conclusions: Enhanced sonifications are more informative than conventional sonification. The implication is that they might allow anaesthetists to judge better when desaturation decreases below, or returns to, a target range.
Asunto(s)
Percepción Auditiva , Alarmas Clínicas , Oximetría/instrumentación , Oximetría/métodos , Oxígeno/metabolismo , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudiantes de Medicina , Análisis y Desempeño de Tareas , Adulto JovenRESUMEN
UNLABELLED: Our study examined the effectiveness of pulse oximetry sonification enhanced with acoustic tremolo and brightness to help listeners differentiate clinically relevant oxygen saturation ranges. In a series of trials lasting 30 s each, 76 undergraduate participants identified final oxygen saturation range ( TARGET: 100% to 97%; Low: 96% to 90%; Critical: 89% and below), and detected threshold transitions into and out of the target range using conventional sonification (n = 38) or enhanced sonification (n = 38). Median (IQR [range]) accuracy for range identification with the conventional sonification was 80 (70-85 [45-95])%, whereas with the enhanced sonification it was 100 (99-100 [80-100])%; p < 0.001. Accuracy for detecting threshold transitions with the conventional sonification was 60 (50-75 [30-95])%, but with the enhanced sonification it was 100 (95-100 [75-100]%; p < 0.001. Participants can identify clinically meaningful oxygen saturation ranges and detect threshold transitions more accurately with enhanced sonification than with conventional sonification.
Asunto(s)
Oximetría/instrumentación , Oximetría/métodos , Oxígeno/sangre , Alarmas Clínicas , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Sonicación , Sonido , Estudiantes de Medicina , Encuestas y Cuestionarios , Adulto JovenRESUMEN
We measured pulmonary function in 21 patients, after craniospinal irradiation with a posterior spinal electron beam. The median age at treatment was 7.5 years. Nine patients (43%) demonstrated abnormal pulmonary function tests, five with restrictive changes, one with isolated diminished diffusion capacity, and three with obstructive disease. These changes were mild and predominantly asymptomatic.
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Neoplasias del Sistema Nervioso Central/radioterapia , Irradiación Craneana/efectos adversos , Neumonitis por Radiación , Radioterapia de Alta Energía/efectos adversos , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Meduloblastoma/radioterapia , Dosificación Radioterapéutica , Pruebas de Función Respiratoria , Columna VertebralRESUMEN
STUDY OBJECTIVE: To compare quality of life and exercise capacity (primary aim), and drug usage (secondary aim), between groups of patients with irreversible chronic airflow limitation (CAL) who were undergoing theophylline Theo-Dur; Key Pharmaceuticals; Kenilworth, NJ) therapy guided by n of 1 trials or standard practice. DESIGN: Randomized study of n of 1 trials vs standard practice. SETTING: Outpatient departments in two tertiary care centers. PATIENTS: Sixty-eight patients with irreversible CAL who were symptomatic despite the use of inhaled bronchodilators, and who were unsure whether theophylline was helping them following open treatment, were randomized into n of 1 trials (N=34) or standard practice. INTERVENTIONS: The n of 1 trials (single-patient, randomized, double-blind, multiple crossover comparisons of the effect on dyspnea of theophylline vs a placebo) followed published guidelines. Standard practice patients stopped taking theophylline but resumed it if their dyspnea worsened. If their dyspnea then improved, theophylline was continued. In both groups, a decision about continuing or stopping the use of theophylline was made within 3 months of randomization. MEASUREMENTS AND RESULTS: The primary outcomes (the chronic respiratory disease questionnaire [CRQ] and 6-min walk) were measured at baseline, 6 months, and 12 months by personnel blinded to treatment group allocation. No between-group differences (n of 1 minus standard practice) were seen in within-group changes over time (1 year minus baseline) in the CRQ Physical Function score (point estimate on the difference, -2.8; 95% confidence limits [CLs], -8.2, 2.5), CRQ Emotional Function score (point estimate on the difference, 0.5; 95% CLs, -4.7, 5.7), or 6-min walk (point estimate on the difference, 8 m; 95% CLs, -26, 44 m). No differences between groups were seen in the secondary outcome of the proportion of patients taking theophylline at 6 and 12 months. In 7 of 34 n of 1 trial patients (21%), dyspnea improved during theophylline treatment compared with placebo treatment. CONCLUSIONS: Using n of 1 trials to guide theophylline therapy in patients with irreversible CAL did not improve their quality of life or exercise capacity, or reduce drug usa e, over 1 year compared to standard practice. Under the objective conditions of an n of 1 trial, 21% of patients with CAL responded to theophylline. There remains a rationale for considering theophylline in patients with irreversible CAL who remain symptomatic despite the use of inhaled bronchodilators, but the use of n of 1 trials to guide this decision did not yield clinically important advantages over standard practice.
Asunto(s)
Broncodilatadores/administración & dosificación , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Teofilina/administración & dosificación , Anciano , Broncodilatadores/efectos adversos , Estudios Cruzados , Método Doble Ciego , Prueba de Esfuerzo/efectos de los fármacos , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Teofilina/efectos adversos , Resultado del Tratamiento , Capacidad Vital/efectos de los fármacosRESUMEN
The effect of NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine methyl ester (L-NAME) on acetylcholine (ACh) induced relaxation of rat intrapulmonary artery and celiac artery ring segments was studied in vitro with and without meclofenamate pretreatment. L-NMMA, and to a lesser extent L-NAME, raised baseline tone more in pulmonary than celiac arteries. Pretreatment of pulmonary and celiac artery rings with meclofenamate did not alter this contractile effect. Pulmonary artery and celiac artery ring segments were precontracted with phenylephrine, and cumulative concentration-relaxation curves to ACh were obtained before and after incubation of the rings with L-NAME or L-NMMA. L-NAME inhibited the ACh-induced relaxation of pulmonary arterial rings at 10000 fold lower concentrations than those needed to only partly inhibit the ACh-induced relaxation of celiac artery rings. L-NMMA (10-300 microM) inhibited the ACh-induced relaxation of pulmonary arterial rings in a concentration-dependent manner, whereas L-NMMA (300 microM) only partially inhibited the ACh-induced relaxation of celiac artery rings. The inhibition of ACh-induced relaxation by L-NAME and to a lesser extent by L-NMMA was more when pulmonary and celiac artery rings were pretreated with meclofenamate (1.0 microM). These results suggest that in the pulmonary artery nitric oxide plays a greater role in the modulation of baseline vascular tone and ACh-induced relaxation than in the celiac artery. In addition, cyclooxygenase products do not contribute to the direct contractile responses to L-NAME and L-NMMA in both the pulmonary and celiac artery rings but do modulate the ACh-induced relaxation of these vessels.
Asunto(s)
Acetilcolina/farmacología , Arteria Celíaca/efectos de los fármacos , Óxido Nítrico Sintasa/antagonistas & inhibidores , Arteria Pulmonar/efectos de los fármacos , Vasodilatación , Animales , Arteria Celíaca/enzimología , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores Enzimáticos/farmacología , Técnicas In Vitro , Masculino , Ácido Meclofenámico/farmacología , Microcirculación/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Arteria Pulmonar/enzimología , Ratas , Ratas Sprague-Dawley , omega-N-Metilarginina/farmacologíaRESUMEN
Insufficient use of anti-inflammatory drugs, such as inhaled corticosteroids and cromoglycate, may contribute to the disease burden associated with asthma. Conversely, aggressive treatment of mild disease may result in avoidable costs and/or adverse drug effects. The aim of this study was to determine the relationship between asthma severity and inhaled corticosteroid/cromoglycate use in a large (n=4,909) random sample of children, aged 8-11 yrs, in NSW, Australia. Asthma and its treatment were assessed by questionnaire responses. Asthma, defined as diagnosis plus current wheeze, was present in 901 children (18% of the sample), of whom 225 (5%) had moderate asthma, defined as asthma plus additional symptoms (sleep disturbance), utilization (hospital, casualty), or disability (reduced activity, school absence). Use of inhaled corticosteroid/cromoglycate was reported by 636 children (13% of the sample). Determinants of use included: asthma diagnosis, current wheeze, and troublesome dry nocturnal cough. There was also a strong relationship between anti-inflammatory treatment and a multicomponent asthma severity score constructed for each child. Inhaled corticosteroids and/or cromoglycate were used by 56% of the children with asthma (24% daily) and by 76% of children with moderate asthma (42% daily). Undertreatment, defined as less than daily inhaled corticosteroids/cromoglycate in moderate asthma, was identified in 130 children (14% of those with asthma or 3% of the sample). Conversely, apparently aggressive treatment, defined as inhaled corticosteroid/cromoglycate use in children with persistent minimal symptoms (asthma severity score of less than 3) was identified in 101 children (2% of the sample). Although there were significant differences between regions in the choice of anti-inflammatory drugs and in the prevalence both of undertreatment and apparently aggressive treatment, there was no clear relationship to regional utilization of emergency and hospital services for asthma. Nevertheless, the frequency of undertreatment suggests an opportunity to reduce asthma morbidity by more consistent application of current therapeutic guidelines.
Asunto(s)
Antiasmáticos/administración & dosificación , Antiinflamatorios/administración & dosificación , Asma/tratamiento farmacológico , Cromolin Sódico/administración & dosificación , Pautas de la Práctica en Medicina , Administración por Inhalación , Antiasmáticos/uso terapéutico , Antiinflamatorios/uso terapéutico , Asma/diagnóstico , Asma/epidemiología , Estudios de Casos y Controles , Niño , Cromolin Sódico/uso terapéutico , Utilización de Medicamentos , Humanos , Nueva Gales del Sur/epidemiología , Prevalencia , Muestreo , Índice de Severidad de la Enfermedad , Esteroides , Encuestas y CuestionariosRESUMEN
We postulated that the attenuated pulmonary and systemic vascular contractility observed in sepsis was secondary to the release of vasodilator prostaglandins. We used the cyclooxygenase inhibitor meclofenamate to inhibit prostaglandin synthesis in an unanesthetized, chronically instrumented model of hyperdynamic sepsis. Sixteen male Sprague-Dawley rats (300-350 g) were randomized to either sepsis induced by cecal ligation and perforation (CLP, n = 8) or a sham procedure (Sham, n = 8). Vascular reactivity was assessed by measuring the hypoxic (FiO2 = 0.08) pulmonary pressor response (HPV), and the systemic pressor response to an intravenous infusion of phenylephrine (1.5-7.5 micrograms/kg/min) before and after the administration of meclofenamate (5 mg/kg intravenously, i.v.). Twenty-four hours postoperatively, CLP animals had significantly increased cardiac output (CO) as compared with Sham animals (204 +/- 12 vs. 148 +/- 5 ml/min, p < 0.05), slightly decreased mean arterial pressure (MAP) (109 +/- 4 vs. 118 +/- 3 mm Hg, p < 0.05), and decreased total systemic vascular resistance (TSVR) (0.546 +/- 0.046 vs. 0.805 +/- 0.030 mm Hg.min.ml-1, p < 0.05). Mean pulmonary artery pressure (MPAP) and total pulmonary vascular resistance (TPVR) were similar in both groups (p > 0.05). In response to hypoxia, the change in MPAP (delta MPAP) was 3.6 +/- 1.0 and 6.9 +/- 0.8 (mm Hg) in CLP and Sham animals, respectively (p < 0.05). Similarly, the change in TPVR (delta TPVR) during hypoxia was 0.012 +/- 0.006 and 0.038 +/- 0.009 mm Hg.min.ml-1 in CLP and Sham (p < 0.05). The pulmonary and systemic blood pressure (BP) response to phenylephrine was also attenuated in CLP as compared with Sham animals. After treatment with meclofenamate, differences were no longer apparent in the HPV response between CLP and Sham animals, due to a slight increase in the HPV response of CLP animals and a slight decrease in the HPV response in Sham animals. The attenuated pressor response to phenylephrine was not changed in either the pulmonary or the systemic circulation after the administration of meclofenamate. These data suggest that vasodilator prostaglandins may contribute to the attenuated pulmonary pressor response in sepsis. However, the mechanism of the attenuated HPV may be different than the attenuated response to exogenous catecholamines since meclofenamate had no effect on either the pulmonary or systemic response to a phenylephrine infusion in septic animals.
Asunto(s)
Inhibidores de la Ciclooxigenasa/farmacología , Hemodinámica/efectos de los fármacos , Ácido Meclofenámico/farmacología , Arteria Pulmonar/efectos de los fármacos , Sepsis/fisiopatología , Animales , Dinoprostona/sangre , Hipoxia/fisiopatología , Masculino , Fenilefrina/farmacología , Arteria Pulmonar/fisiología , Ratas , Ratas Sprague-Dawley , Tromboxano B2/sangre , Vasoconstricción , Vasoconstrictores/farmacologíaRESUMEN
Abnormal systemic and pulmonary vascular reactivity has been demonstrated in numerous models of sepsis and pneumonia. Furthermore, the attenuated hypoxic pulmonary pressor response observed in these animals probably is responsible for the ventilation/perfusion (V/Q) mismatching and consequent arterial hypoxemia. We hypothesized that excess release of endogenous vasodilators such as calcitonin gene-related peptide (CGRP) in pneumonia was responsible for the diminished hypoxic pressor response. Using the CGRP receptor antagonist CGRP (8-37), we examined the role of CGRP in the attenuated hypoxic pulmonary response in a rat model of acute Pseudomonas pneumonia. Sixteen Sprague-Dawley rats were instrumented for chronic hemodynamic monitoring and subsequently randomized to either Pneumonia (n = 8), induced by the instillation of 0.2 ml broth containing 2 x 10(8) colony-forming units (CFU)/ml Pseudomonas aeruginosa into the right lower lobe, or Sham (n = 8) procedure. Hemodynamic measurements and the hypoxic (FiO2 = 0.08) pulmonary pressor response were recorded at baseline, 48 h after the pneumonia or sham procedure and after the administration of 250 micrograms CGRP (8-37) (post-CGRP(8-37)). The regional distribution of pulmonary blood flow was determined by the injection of radioactive microspheres. Forty-eight hours after the instillation of Pseudomonas, Pneumonia animals had significantly increased cardiac output (CO) as compared with Sham (193 +/- 7 vs. 154 +/- 7 ml/min, p < 0.05), slightly decreased mean arterial pressure (MAP 109 +/- 4 vs. 118 +/- 3 mm Hg, p = NS), and reduced total systemic vascular resistance (TSVR 0.57 +/- 0.03 vs. 0.78 +/- 0.05 mm Hg.min.ml-1, p < 0.05). Pneumonia animals were further characterized by increased mean pulmonary artery pressure (MPAP) as compared with Sham (24 +/- 2 vs. 20 +/- 1 mm Hg, p < 0.05) animals, and an increased alveolar-arterial (A-a) oxygen gradient (31 +/- 3 vs. 20 +/- 4 mm Hg, p < 0.05). The administration of CGRP (8-37) did not alter baseline hemodynamic variables and did not change the pressor response to hypoxia in either group. Furthermore, CGRP receptor blockade did not alter the distribution of blood flow in the lung during normoxia or hypoxia. These data suggest that although this model of acute pneumonia is characterized by an attenuated hypoxic pressor response, the mechanism does not appear to be mediated by excess release of the vasodilator CGRP.
Asunto(s)
Péptido Relacionado con Gen de Calcitonina/farmacología , Pulmón/irrigación sanguínea , Fragmentos de Péptidos/farmacología , Neumonía Bacteriana/fisiopatología , Pseudomonas aeruginosa , Animales , Relación Dosis-Respuesta a Droga , Hemodinámica/efectos de los fármacos , Hipoxia/fisiopatología , Pulmón/efectos de los fármacos , Fenilefrina/farmacología , Ratas , Vasoconstrictores/farmacología , Relación Ventilacion-Perfusión/efectos de los fármacosRESUMEN
We have previously reported differential impairment of pulmonary and systemic vascular contractility in hyperdynamic sepsis. The objectives of this study were (1) to determine whether the magnitude of this phenomenon depends on the control group chosen for comparison, and (2) to examine the role of nitric oxide (NO) in this altered vascular contractility. Rats were randomized to sepsis induced by cecal ligation and perforation (CLP) or to one of two control procedures. The Sepsis group had a jugular venous line for fluid administration, laparotomy, and CLP. Control group 1 (Control) had only a jugular venous line inserted, while group 2 (Sham) had a jugular venous line inserted and an abdominal incision. All rats were killed 24 h after surgery. Vascular contractility of small pulmonary arterial and thoracic aortic rings was assessed in vitro by obtaining cumulative dose-response curves to the contractile agonists potassium chloride (KCl), phenylephrine (PE), and prostaglandin F2 alpha (PGF2 alpha). Pulmonary vessels from animals in the Sepsis and Sham groups exhibited significant attenuation of the contractile responses to KCl, PE, and PGF2 alpha compared with the Control group. In contrast, contractility of the aortic rings to KCl, PE, and PGF2 alpha was not significantly different in the three groups studied. Incubation of pulmonary and aortic vessels with NG-nitro-L-argine methyl ester (L-NAME, 10 microM) caused an increase in the response to KCl, PE, and PGF2 alpha in pulmonary vessels in Sepsis and Sham rats but not in Control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Músculo Liso Vascular/fisiología , Óxido Nítrico/fisiología , Sepsis/fisiopatología , Resistencia Vascular/fisiología , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiopatología , Arginina/análogos & derivados , Arginina/farmacología , Cateterismo Venoso Central , Ciego/lesiones , Perforación Intestinal/fisiopatología , Masculino , Músculo Liso Vascular/efectos de los fármacos , NG-Nitroarginina Metil Éster , Óxido Nítrico/antagonistas & inhibidores , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/fisiopatología , Ratas , Ratas Sprague-Dawley , Resistencia Vascular/efectos de los fármacosRESUMEN
To evaluate the role of nitric oxide (NO) in the attenuated vascular reactivity observed in sepsis, we utilized the specific NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Male Sprague-Dawley rats (n = 16) were randomized to either sepsis induced by cecal ligation and perforation (CLP; n = 8) or sham procedure (Sham; n = 8). Vascular reactivity was assessed by measuring the pulmonary pressor response to hypoxia (HPV) (fractional inspired O2 concentration = 0.08) and the pulmonary and systemic pressor response to an intravenous infusion of phenylephrine (1.5-6.0 micrograms.kg-1.min-1). Twenty-four hours after surgery, CLP animals had significantly attenuated HPV compared with Sham animals. In response to hypoxia the change in total pulmonary vascular resistance during hypoxia was 0.008 +/- 0.004 and 0.021 +/- 0.006 mmHg.min-ml-1 in CLP and Sham animals, respectively (P < 0.05). The pulmonary and systemic blood pressure response to phenylephrine was also attenuated in CLP compared with Sham animals. After L-NAME infusion (15 mg/kg), there was a significant augmentation of the HPV response in Sham animals. In contrast, the HPV response in CLP animals was unchanged after L-NAME. The attenuated pressor response to phenylephrine in neither the pulmonary nor the systemic circulation was changed after the administration of L-NAME. These data suggest that in rats, excess NO is not an important mediator of the attenuated vascular reactivity observed in sepsis.
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Aminoácido Oxidorreductasas/antagonistas & inhibidores , Arginina/análogos & derivados , Hemodinámica/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Arteria Pulmonar/efectos de los fármacos , Sepsis/fisiopatología , Animales , Arginina/farmacología , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Hipoxia/fisiopatología , Infusiones Intravenosas , Masculino , Músculo Liso Vascular/fisiología , NG-Nitroarginina Metil Éster , Óxido Nítrico Sintasa , Fenilefrina/administración & dosificación , Fenilefrina/farmacología , Arteria Pulmonar/fisiología , Arteria Pulmonar/fisiopatología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Resistencia Vascular/efectos de los fármacosRESUMEN
The clinical, functional, radiologic, and pathologic characteristics of seven cases of necrotizing sarcoid granulomatosis (NSG) are presented. The population consisted of five women and two men, with an average age of 36 years. Each patient's predominant presenting complaint was pleuritic chest pain. Pulmonary function testing demonstrated a variety of abnormal patterns. Computed tomography (CT) of the chest showed solitary or multiple nodules in all patients, occasionally associated with pulmonary infiltrates in the lower lobes. Pleural involvement was seen on CT scanning in six patients and mediastinal adenopathy was present in five. Biopsy specimens of the lung lesions revealed confluent epithelioid granulomata associated with necrosis and vasculitis. Pleural involvement by confluent granulomata was a prominent feature in four patients. Follow-up has ranged from 6 months to 4 years. All patients are now asymptomatic, the majority having received prednisone. One patient received methotrexate as a steroid-sparing measure. We conclude that NSG is distinguishable from sarcoidosis as a clinicopathologic entity in which pleural involvement is a frequent finding. Treatment with steroids appears to hasten recovery.
Asunto(s)
Enfermedades Pleurales/patología , Sarcoidosis Pulmonar/patología , Adulto , Biopsia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Necrosis , Pleura/diagnóstico por imagen , Pleura/patología , Enfermedades Pleurales/diagnóstico por imagen , Enfermedades Pleurales/epidemiología , Enfermedades Pleurales/terapia , Pruebas de Función Respiratoria , Estudios Retrospectivos , Sarcoidosis Pulmonar/diagnóstico por imagen , Sarcoidosis Pulmonar/epidemiología , Sarcoidosis Pulmonar/terapia , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
In pulmonary inflammatory processes such as pneumonia there is diminished hypoxic pulmonary vasoconstriction (HPV). We investigated whether the attenuated HPV in pneumonia is a due to excess nitric oxide (NO) release. Sprague-Dawley rats were anesthetized, and a slurry (0.06 ml) of infected agar beads (containing 6 x 10(5) Pseudomonas aeruginosa organisms) or control (sterile) beads was then injected into a distal bronchus through a tracheotomy. After the establishment of a chronic P. aeruginosa pneumonia (7-10 days later) animals were instrumented for hemodynamic monitoring, and the response to exposure to hypoxic gas (fraction of inspired O2 = 0.08) was recorded before and after the administration of NG-monomethyl-L-arginine (L-NMMA; 50 mg/kg), an inhibitor of NO synthesis. The hypoxic pressor response, as assessed by the absolute increase in pulmonary arterial pressure (PAP) and total pulmonary resistance (TPR), was reduced in infected animals compared with control animals. The change in PAP and TPR was 8.5 +/- 0.7 and 0.053 +/- 0.007, respectively, in control animals compared with 5.9 +/- 0.5 and 0.041 +/- 0.011 in infected animals. After L-NMMA the increase in PAP and TPR during hypoxia was greater in both control and infected animals. However, treatment with L-NMMA did not affect the difference between control and infected animals. We conclude that excess release of NO does not account for the attenuated hypoxic pressor response in pneumonia.
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Hemodinámica , Óxido Nítrico/fisiología , Neumonía/fisiopatología , Infecciones por Pseudomonas/fisiopatología , Arteria Pulmonar/fisiopatología , Vasoconstricción/fisiología , Animales , Arginina/análogos & derivados , Arginina/farmacología , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Hipoxia/fisiopatología , Inflamación , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Músculo Liso Vascular/fisiopatología , Infecciones por Pseudomonas/metabolismo , Pseudomonas aeruginosa , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/fisiología , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/efectos de los fármacos , Resistencia Vascular/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , omega-N-MetilargininaRESUMEN
Chronic Pseudomonas pneumonia is associated with decreased acute hypoxic pulmonary vasoconstriction. However, it is not known whether this is a result of a generalized reduction in contractile responsiveness. We therefore examined the effect of chronic Pseudomonas pneumonia on in vitro pulmonary vascular responsiveness to agonists. We then investigated the role of nitric oxide (NO) in the altered pulmonary vascular contractility. Control rats or rats infected with Pseudomonas (pneumonia) were killed, and small intrapulmonary arteries (100-200 microns effective lumen radius) were removed. In the pneumonia group, arteries were harvested from the pneumonic area of the lung. Vascular responsiveness was assessed in vitro by obtaining cumulative dose-response curves to contractile agonists [phenylephrine (PE), 5-hydroxytryptamine (5-HT), prostaglandin F2 alpha (PGF2 alpha), and KCl]. KCL-induced (voltage-operated) contractions were not significantly depressed in small pulmonary arteries from pneumonic lungs, suggesting that the smooth muscle contractile apparatus in these arteries was preserved. Contractile responses to the three receptor-operated agonists (PE, 5-HT, and PGF2 alpha) were significantly depressed in arteries subserving the pneumonic lobe of infected rats. NG-monomethyl-L-arginine, which blocks the synthesis of NO, caused a shift toward the left in the dose-contraction curves to PE, PGF2 alpha, and 5-HT in vessels from the sterile control lungs, but it had little effect on arteries from the pneumonic lungs. Chronic Pseudomonas pneumonia is associated with depressed pulmonary vascular contractility in vitro, particularly affecting the receptor-mediated contractile responses. Excessive NO release does not contribute to this attenuated vascular contractility.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Óxido Nítrico/fisiología , Neumonía/fisiopatología , Circulación Pulmonar/fisiología , Acetilcolina/farmacología , Animales , Arginina/análogos & derivados , Arginina/farmacología , Enfermedad Crónica , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacología , Neumonía/microbiología , Infecciones por Pseudomonas , Circulación Pulmonar/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Vasoconstrictores/farmacología , omega-N-MetilargininaRESUMEN
We postulated that the redistribution of organ blood flow that occurs in hyperdynamic sepsis is secondary to organ-specific alterations in vascular reactivity. Chronically instrumented rats were randomized to cecal ligation and perforation (CLP) (n = 12) or to a control procedure (n = 11). Cardiac output increased from 107 +/- 23 ml/min at baseline to 152 +/- 32 ml/min at 24 h after CLP (p = 0.037 versus control values). Mean blood pressure did not change in either group. Small arterial ring segment (100- to 200-microns effective lumen radius) from the pulmonary, renal, celiac, and femora arteries were obtained for determination of in vitro responsiveness. Maximal contractile responses to three receptor-operated contractile agonists were significantly depressed in the pulmonary (p = 0.001) and the celiac (p = 0.001) arteries from CLP versus control rats. The renal artery showed a trend toward decreased responsiveness (p = 0.049), but not difference was seen in the femoral artery (p = 0.172). EC50 values were unchanged. A similar, but less marked, pattern was observed for KCI-induced contractions in that depressed responses were noted in the pulmonary (p = 0.045) and celiac (p = 0.064) arteries. Vasodilator responses to acetylcholine were normal in all vessels. Nitroprusside relaxant responses were enhanced in the pulmonary artery (p = 0.022), but they were normal in the other vessels. We conclude that hyperdynamic, normotensive sepsis is associated with an organ-specific alteration of vascular smooth muscle function that particularly affects receptor-operated contractile responses. The differential expression of this altered vascular responsiveness between organs may contribute to the observed variance in regional blood flows in sepsis.
Asunto(s)
Arteria Celíaca/fisiopatología , Arteria Femoral/fisiopatología , Arteria Pulmonar/fisiopatología , Arteria Renal/fisiopatología , Choque Séptico/fisiopatología , Resistencia Vascular/efectos de los fármacos , Animales , Cateterismo Periférico/instrumentación , Cateterismo Periférico/métodos , Ciego/lesiones , Ciego/fisiología , Arteria Celíaca/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Arteria Femoral/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Perforación Intestinal/fisiopatología , Ligadura , Masculino , Arteria Pulmonar/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Arteria Renal/efectos de los fármacosRESUMEN
In human blood, cortisol is transported by a plasma protein known as corticosteroid-binding globulin (CBG). As anticipated from primary structure comparisons of CBG and alpha 1-proteinase inhibitor (A1-PI), CBG acts as a substrate for neutrophil elastase. However, unlike A1-PI, CBG does not alter the activity of this enzyme, but is cleaved by it at a single location close to its carboxy-terminus, and this reduces its molecular size by 5 kDa with the concomitant release of more than 80% of CBG-bound cortisol. Three small molecular size fragments are detected after elastase cleavage, and carbohydrate analysis of these fragments suggests that they represent the same polypeptide fragment which has been differentially glycosylated. To assess the biological significance of these observations, CBG was incubated with either mononuclear cells or granulocytes obtained from patients with acute inflammation (sepsis) and from a normal volunteer. Only granulocytes from septic patients reduced the mol wt of CBG by about 5 kDa and destroyed its steroid-binding activity. Preincubation with A1-PI prevented this, which demonstrates that neutrophil elastase plays a key role in this event. These results suggest a physiological role for CBG in the delivery of cortisol to sites of inflammation.
Asunto(s)
Hidrocortisona/metabolismo , Neutrófilos/metabolismo , Transcortina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Transporte Biológico , Metabolismo de los Hidratos de Carbono , Electroforesis en Gel de Poliacrilamida , Activación Enzimática/efectos de los fármacos , Femenino , Granulocitos/metabolismo , Humanos , Inflamación/metabolismo , Leucocitos Mononucleares/metabolismo , Masculino , Elastasa Pancreática/metabolismo , Fragmentos de Péptidos/metabolismo , alfa 1-Antitripsina/metabolismoRESUMEN
Because small pulmonary arteries are believed to be the major site of hypoxic pulmonary vasoconstriction (HPV), pulmonary venular responses to hypoxia have received little attention. Therefore the responses of isolated guinea pig pulmonary venules to hypoxia (bath PO2, 25 Torr) and anoxia (bath PO2, 0 Torr) were characterized. Pulmonary venules [effective lumen radius (ELR), 116 +/- 2 microns] with an adherent layer of parenchyma responded to hypoxia and anoxia with a graded sustained contraction (hypoxia, 0.03 +/- 0.01; anoxia, 0.26 +/- 0.03 mN/mm), whereas paired femoral venules (ELR, 184 +/- 7 microns) contracted to anoxia only (0.05 +/- 0.02 mN/mm). Repeated challenges with hypoxia and anoxia continued to elicit sustained pulmonary venular contractions; femoral venule contractions to anoxia were not repeatable. Hypoxia- and anoxia-induced pulmonary venular contractions were calcium and pH dependent. Dissection of the parenchyma from pulmonary venules did not alter contractions to decreased PO2. Anoxic contractions of pulmonary venules were variably reduced by replacement of the bath fluid; however, the release of a contractile mediator(s) from pulmonary venules during hypoxia or anoxia was not demonstrated. Pulmonary venular responses to hypoxia and anoxia are similar to those induced by hypoxia in vivo, and results obtained from this model may be useful in predicting mechanisms of HPV.
Asunto(s)
Oxígeno/fisiología , Venas Pulmonares/fisiología , Vasoconstricción/fisiología , Animales , Calcio/fisiología , Capilares/fisiología , Vena Femoral/fisiología , Cobayas , Concentración de Iones de Hidrógeno , Hipoxia , Técnicas In Vitro , Masculino , Venas Pulmonares/anatomía & histología , Venas Pulmonares/efectos de los fármacos , Vasoconstricción/efectos de los fármacosRESUMEN
Arachidonic acid metabolites, notably leukotrienes (LTs), have been postulated to play a role in hypoxic pulmonary vasoconstriction. In the present study, we examined the contribution of arachidonic acid metabolites, via the cyclooxygenase, 5-lipoxygenase and cytochrome P-450 monooxygenase pathways, to the hypoxia (25 +/- 3 torr)- and anoxia (0 +/- 2 torr)-induced contractions of isolated pulmonary venules. Neither the cyclooxygenase inhibitors indomethacin (5 microM) or ibuprofen (10 microM) nor the 5-lipoxygenase inhibitors nordihydroguaiaretic acid (5 microM) or U 60257B (10 microM) affected the contractile responses. Similarly, the LT receptor antagonists FPL 57231 (3 microM) or LY 163443 (1 microM), at concentrations that inhibited LT-induced venular contractions, did not significantly affect the responses to hypoxia or anoxia. In fact, anoxia suppressed spontaneous LT release from the venules. The cytochrome P-450 inhibitor SKF-525A (500 microM) nonselectively depressed venular contractions induced by decreased PO2 and pharmacological agents. Induction of the cytochrome P-450 monooxygenase system with beta-naphthoflavone did not alter venular contractions induced by hypoxia or anoxia. Contractions of isolated guinea pig pulmonary venules elicited by decreased PO2 are not mediated by 5-lipoxygenase or cyclooxygenase metabolites. Furthermore, the data do not support a role for cytochrome P-450 metabolites of endogenous substrates in these contractions.
Asunto(s)
Sistema Enzimático del Citocromo P-450/fisiología , Hipoxia/fisiopatología , Leucotrienos/fisiología , Lipooxigenasa/fisiología , Pulmón/irrigación sanguínea , Prostaglandina-Endoperóxido Sintasas/fisiología , Venas/fisiología , Vénulas/fisiología , Acetofenonas/farmacología , Animales , Benzoflavonas/farmacología , Calcimicina/farmacología , Cromonas/farmacología , Epoprostenol/farmacología , Cobayas , Leucotrienos/farmacología , Inhibidores de la Lipooxigenasa , Masoprocol/farmacología , Contracción Muscular/efectos de los fármacos , Músculos , Piridinas/farmacología , beta-naftoflavonaRESUMEN
The influence of the endothelium on pulmonary venular responses to reduced oxygen tension has not been defined. To examine this question, endothelial injury was induced in small guinea pig pulmonary artery and venule segments (effective lumen radius, 174 +/- 5 and 122 +/- 2 microns, respectively) by perfusion with either a mixture of hypoxanthine (5 mM) and xanthine oxidase (0.05 U/ml) (HX/XO) or collagenase (2 mg/ml). HX/XO significantly (p less than 0.05) reduced the relaxation of precontracted pulmonary arteries by acetylcholine (ACH), bradykinin (BK), and A-23187, and the relaxations were restored by including superoxide dismutase (40 micrograms/ml) in the HX/XO solution. However, neither HX/XO nor collagenase affected vasodilation induced by ACH, BK, and A-23187 in precontracted pulmonary venules. In contrast, HX/XO significantly (p less than 0.05) augmented the sustained contraction of pulmonary venules to hypoxia (HX/XO, 3.2 +/- 1.0 mg/mm; control, 1.0 +/- 0.5 mg/mm) and anoxia (HX/XO, 35.1 +/- 6.6 mg/mm; control, 20.3 +/- 4.0 mg/mm). Collagenase also significantly (p less than 0.05) enhanced the anoxic contractions (collagenase, 36.0 +/- 3.7 mg/mm; control, 20.9 +/- 6.8 mg/mm). Superoxide dismutase (40 micrograms/ml) and catalase (323 micrograms/ml) abolished HX-XO-induced augmentation of the hypoxic and anoxic contractions of pulmonary venules. Collagenase removed 54 +/- 8% of the venular endothelium (control, 5 +/- 1%), whereas HX/XO-exposed endothelial cells contained numerous craters. Neither gossypol (5 microM) nor methylene blue (10 microM) affected pulmonary venular contractions to reduced PO2. Endothelial damage augments the PO2-dependent contractions of the pulmonary venule, and this augmentation does not appear to be due to decreased release of endothelium-derived relaxing factor.