RESUMEN
BACKGROUND: Obstructive sleep apnea syndrome (OSAS) has emerged as a risk factor for cardiovascular disease. A prothrombotic state may affect coagulation and participate in the atherosclerotic process in subjects with OSAS. These alterations in coagulation seem to involve the plasminogen activation system. We evaluated the imbalances of the plasminogen activation system related to OSAS, and we assessed the effects of CPAP on the plasminogen activation system. METHODS: Thirty-nine subjects were submitted to a home-based cardiorespiratory sleep study, and 14 healthy subjects (apnea-hypopnea index < 5) were used as controls. Serum levels of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and active transforming growth factor-ß (TGF-ß) were measured. These molecules were reassessed in only 17 of the subjects after 1 month of CPAP. RESULTS: PAI-1 and tPA were significantly higher in the subjects with OSAS compared with the controls, whereas TGF-ß and uPA levels were lower. PAI-1 showed a significant positive correlation with the apnea-hypopnea index, percentage of time spent at O2 saturation < 90%, and oxygen desaturation index, whereas TGF-ß was inversely related to all 3 of these parameters. After the CPAP therapy, PAI-1 significantly decreased, whereas TGF-ß showed a significant increase, although the values did not reach those of the controls. uPA and tPA did not show significant differences after the treatment. CONCLUSIONS: Our results suggest an imbalance of fibrinolysis related to OSAS and an improvement of the prothrombotic state after the CPAP treatment.
Asunto(s)
Inhibidor 1 de Activador Plasminogénico/sangre , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/terapia , Activador de Tejido Plasminógeno/sangre , Factor de Crecimiento Transformador beta/sangre , Activador de Plasminógeno de Tipo Uroquinasa/sangre , Anciano , Estudios de Casos y Controles , Presión de las Vías Aéreas Positiva Contínua , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/complicaciones , Trombofilia/sangre , Trombofilia/etiologíaRESUMEN
UNLABELLED: Incremental cardiopulmonary exercise test with gas exchange measurement is the gold standard for the identification of the ventilatory compensation point (VCP). It has previously been demonstrated that the change in the slope of increment of minute ventilation over HR (ΔVËE/ΔHR) can be used alternatively to the ventilatory equivalent for CO2 (VËE/VËCO2) method for detection of VCP in healthy subjects undergoing cycle ergometer (C) incremental exercise. The same evaluation during treadmill (T) incremental exercise and comparison between C and T have not yet been performed. PURPOSE: We analyzed, during both C and T incremental exercises, the VËE/HR and the respiratory rate (RR)/HR relationships, expressed either as slope or as an absolute value. We hypothesized that changes in the slope of increment of the two relationships could represent a reliable method for VCP detection, regardless of exercise mode and protocol. METHODS: Fourteen healthy male subjects (age = 31 ± 7 yr (mean ± SD)) underwent two T incremental exercises--fast (FT) and slow (ST) protocols (8 km·h⻹, 2% (F(T)) and 1% (S(T)) grade per minute)--and one C incremental exercise (30 W·min⻹). O2 uptake (VËO2), VËCO2, VËE, HR, and RR were measured breath by breath. RESULTS: A good between-method agreement in the detection of VCP by the ΔVË(E)/ΔVËCO2, ΔVË(E)/ΔHR, and the ΔRR/ΔHR slope changes was found in both T protocols and C. No differences (C vs T and F(T) vs S(T)) were found in the slope of the ΔVË(E)/ΔHR and ΔRR/ΔHR relationships after the VCP and in the VË(E)/HR and RR/HR absolute values at VCP. CONCLUSIONS: In healthy young males, the ΔVËE/ΔHR and ΔRR/ΔHR relationships during T and C incremental exercises can be reliably used to detect the VCP as an alternative to the ventilatory equivalent method.
Asunto(s)
Consumo de Oxígeno/fisiología , Adulto , Umbral Anaerobio/fisiología , Dióxido de Carbono/metabolismo , Dióxido de Carbono/fisiología , Prueba de Esfuerzo , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Intercambio Gaseoso Pulmonar/fisiología , Ventilación Pulmonar/fisiología , Fenómenos Fisiológicos Respiratorios , Adulto JovenRESUMEN
Macrophages play a pivotal role in a host's defence against pulmonary infections. Macrophage functions are impaired in immunosuppressed (IS) patients, regardless of whether they are HIV-positive (HIV+) or -negative (HIV-). Several studies have indicated that urokinase plasminogen activator (uPA) and transforming growth factor beta (TGF-beta) are important factors in a host's defence against pulmonary pathogens. We measured uPA and TGF-beta activity in unstimulated peripheral blood monocytes (PBM) of both HIV-infected and non-infected IS patients with or without Pneumocystis jiroveci (formerly carinii) pneumonia (PCP). As previously found in alveolar macrophages (AMs), the majority of uPA activity was found in cell lysates. The highest values of uPA activity were found in control subjects. All the patients displayed a decreased production of uPA, irrespective of HIV infection. Similarly, active TGF-beta was higher in control subjects than in HIV+ and IS patients. The presence of P. jiroveci infection further lowered uPA and TGF-beta activity. Decreased TGF-beta activation might be a consequence of lower uPA production, which may, in turn, influence virus replication, since it has been demonstrated that TGF-beta can suppress human HIV expression in monocytes/macrophages. Further studies are warranted to elucidate whether the decrease in uPA and TGF-beta activity impairs a host's defence against P. jiroveci infection.