RESUMEN
Intratracheal administration of lipopolysaccharide (LPS) in animals is a commonly used model of acute lung injury, characterized by increased alveolar-capillary membrane permeability causing protein-rich edema, inflammation, deterioration of lung mechanical function and impaired gas exchange. Technetium-99-m-labeled diethylene-triamine pentaacetatic acid ((99m)Tc-DTPA) scintigraphy is a non-invasive technique to assess lung epithelial permeability. We hypothesize that the longer the exposure and the higher the dose of LPS the greater the derangement of the various indices of lung injury. After 3, 6 and 24 h of 5 or 40 µg LPS intratracheally administration, (99m)Tc-DTPA was instilled in the lung. Images were acquired for 90 min with a γ-camera and the radiotracer clearance was estimated. In another subgroup, the mechanical properties of the respiratory system were estimated with the forced oscillation technique and static pressure-volume curves, 4.5, 7.5 and 25.5 h post-LPS (iso-times with the end of (99m)Tc-DTPA scintigraphy). Bronchoalveolar lavage (BAL) was performed and a lung injury score was estimated by histology. Lung myeloperoxidase (MPO) activity was measured. (99m)Tc-DTPA clearance increased in all LPS challenged groups compared with control. DTPA clearance presented a U-shape time course at the lower dose, while LPS had a declining effect over time at the larger dose. At 7.5 and 25.5 h post-LPS, tissue elasticity was increased and static compliance decreased at both doses. Total protein in the BAL fluid increased at both doses only at 4.5 h Total lung injury score and MPO activity were elevated in all LPS-treated groups. There is differential time- and dose-dependency of the various indices of lung injury after intratracheally LPS instillation in rats.
Asunto(s)
Lipopolisacáridos/toxicidad , Neumonía/patología , Sistema Respiratorio/fisiopatología , Pentetato de Tecnecio Tc 99m/farmacocinética , Animales , Líquido del Lavado Bronquioalveolar/química , Elasticidad , Histocitoquímica , Lipopolisacáridos/administración & dosificación , Pulmón/diagnóstico por imagen , Pulmón/patología , Tasa de Depuración Metabólica , Peroxidasa/análisis , Proteínas/análisis , Radiografía , Cintigrafía/métodos , RatasRESUMEN
BACKGROUND: Patients who suffer from obstructive sleep apnea (OSA) have a decreased exercise capacity and abnormal autonomic nervous function. However, the kinetics of early oxygen (O2) and heart rate recovery (HRR) have not been described. MATERIALS AND METHODS: We evaluated 21 men with moderate to severe OSA (mean age: 48 +/- 11 yrs, mean apnea-hypopnea index [AHI]: 55 +/- 13) and without known heart disease and 10 healthy men matched for age and body mass index (BMI; controls). Men with OSA underwent overnight polysomnography, and both groups underwent symptom-limited incremental cardiopulmonary exercise testing (CPET). We recorded the CPET parameters including peak O2 uptake (VO2p), kinetics of early O2 recovery by the first degree slope of VO2 during the first minute (VO2/t slope), the time required for a 50% decline of VO2p during recovery (T(1/2)), and early heart rate recovery (HRR = HR at maximal exercise - HR at 1 min of recovery), as well as the chronotropic reserve to exercise ([CR] = [peak HR - resting HR/220 - age - resting HR] x 100). Patients with OSA had a lower VO2p (28.7 +/- 4.0 vs 34.7 +/- 6.2 mL/kg/min), VO2/t slope (1.04 +/- 0.3 vs 1.4 +/- 0.17 mL/kg/min2), and T(1/2) (74 +/- 10 vs 56 +/- 6 sec) compared to controls (all P < 0.001). In addition, both HRR and CR were lower in the OSA group (22.0 +/- 7.0 vs 31.0 +/- 6.0 bpm, P:0.003, and 79.0% +/- 15% vs 99.0% +/- 13.0%, P:0.01, respectively). CONCLUSIONS: Patients with OSA demonstrate reduced exercise capacity, delayed oxygen kinetics, and reduced HRR. These data point to abnormal oxygen delivery and/or oxidative function of the peripheral muscles and impaired autonomic nervous activity in OSA patients.
Asunto(s)
Adaptación Fisiológica , Ejercicio Físico , Frecuencia Cardíaca , Consumo de Oxígeno , Oxígeno/metabolismo , Apnea Obstructiva del Sueño/fisiopatología , Adulto , Sistema Nervioso Autónomo , Índice de Masa Corporal , Estudios de Casos y Controles , Prueba de Esfuerzo , Tolerancia al Ejercicio , Indicadores de Salud , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Polisomnografía , Pruebas de Función Respiratoria , Estadística como AsuntoRESUMEN
OBJECTIVES: The aim of this study was to estimate the clinical efficacy of counseling combined with currently used pharmacotherapy for smoking cessation (bupropion SR and nicotine replacement therapy, NRT) in actual clinical practice, and to identify predictors of successful abstinence at the end of therapy, as well as predictors of sustained abstinence in one year. METHODS: 895 smokers, self-motivated to quit, received bupropion SR for 7 or 19 weeks and/or nicotine replacement therapy (NRT) (nicotine patch) for 9 weeks in combination with individual behavioural therapy. An intensive program including repetitive visits and telephone contacts during treatment and one year's follow-up period was available for supporting and motivating smokers to prevent relapse. RESULTS: Post-treatment abstinence rates were 71.6% and 53.2% in bupropion SR groups for 7 and 19 weeks of treatment, respectively, (p < 0.001), 63.4% in bupropion SR plus nicotine patch group and 45% (p < 0.001) in nicotine patch group. One year's follow-up abstinence rates were 43.1%, 29.6%, 30.4% and 18.4% (p < 0.05), respectively. Predictors of successful abstinence at the end of therapy included (a) bupropion SR, (b) lower DSM IV symptom score, and (c) lower nicotine addiction, while predictors for sustained abstinence in one year included: (a) bupropion SR, (b) lower nicotine addiction, and (c) smoker's motivation. CONCLUSIONS: Smoking cessation interventions implementing intensive multi-component programs and constant smokers' motivation in health care settings of actual practice seem promising for increasing short and long-term abstinence rates.