Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 101
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Sci Rep ; 12(1): 2283, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35145193

RESUMO

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two forms of pulmonary hypertension (PH) characterized by obstructive vasculopathy. Endothelial dysfunction along with metabolic changes towards increased glycolysis are important in PAH pathophysiology. Less is known about such abnormalities in endothelial cells (ECs) from CTEPH patients. This study provides a systematic metabolic comparison of ECs derived from CTEPH and PAH patients. Metabolic gene expression was studied using qPCR in cultured CTEPH-EC and PAH-EC. Western blot analyses were done for HK2, LDHA, PDHA1, PDK and G6PD. Basal viability of CTEPH-EC and PAH-EC with the incubation with metabolic inhibitors was measured using colorimetric viability assays. Human pulmonary artery endothelial cells (HPAEC) were used as healthy controls. Whereas PAH-EC showed significant higher mRNA levels of GLUT1, HK2, LDHA, PDHA1 and GLUD1 metabolic enzymes compared to HPAEC, CTEPH-EC did not. Oxidative phosphorylation associated proteins had an increased expression in PAH-EC compared to CTEPH-EC and HPAEC. PAH-EC, CTEPH-EC and HPAEC presented similar HOXD macrovascular gene expression. Metabolic inhibitors showed a dose-dependent reduction in viability in all three groups, predominantly in PAH-EC. A different metabolic profile is present in CTEPH-EC compared to PAH-EC and suggests differences in molecular mechanisms important in the disease pathology and treatment.


Assuntos
Células Endoteliais/metabolismo , Hipertensão Arterial Pulmonar/genética , Hipertensão Arterial Pulmonar/metabolismo , Embolia Pulmonar/genética , Embolia Pulmonar/metabolismo , Adulto , Idoso , Células Cultivadas , Doença Crônica , Feminino , Expressão Gênica , Glutamato Desidrogenase/genética , Glutamato Desidrogenase/metabolismo , Glicólise/genética , Hexoquinase/genética , Hexoquinase/metabolismo , Humanos , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Fosforilação Oxidativa , Artéria Pulmonar/citologia , Piruvato Desidrogenase (Lipoamida)/genética , Piruvato Desidrogenase (Lipoamida)/metabolismo
2.
Eur Respir J ; 38(3): 617-27, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21310874

RESUMO

Cigarette smoke (CS) and chronic hypoxia (CH) can produce pulmonary hypertension. Similarities and differences between both exposures and their interaction have not been explored. The aim of the present study was to investigate the effects of CS and CH, as single factors or in combination, on the pulmonary circulation in the guinea pig. 51 guinea pigs were exposed to CS for 12 weeks and 32 were sham-exposed. 50% of the animals in each group were additionally exposed to CH for the final 2 weeks. We measured pulmonary artery pressure (P(pa)), and the weight ratio between the right ventricle (RV) and left ventricle plus the septum. Pulmonary artery contractility in response to noradrenaline (NA), endothelium-dependent vasodilatation and distensibility were evaluated in organ bath chambers. The number of small intrapulmonary vessels showing immunoreactivity to smooth muscle (SM) α-actin and double elastic laminas was assessed microscopically. CS and CH induced similar increases of P(pa) and RV hypertrophy (p<0.05 for both), effects that were further enhanced when both factors were combined. CH increased the contractility to NA (p<0.01) and reduced the distensibility (p<0.05) of pulmonary arteries. Animals exposed to CS showed an increased number of small vessels with positive immunoreactivity to SM α-actin (p<0.01) and those exposed to CH a greater proportion of vessels with double elastic laminas (p<0.05). We conclude that CH amplifies the detrimental effects of CS on the pulmonary circulation by altering the mechanical properties of pulmonary arteries and enhancing the remodelling of pulmonary arterioles.


Assuntos
Hipóxia , Circulação Pulmonar/efeitos dos fármacos , Fumar , Animais , Aorta/patologia , Peso Corporal , Proliferação de Células , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Cobaias , Ventrículos do Coração/efeitos dos fármacos , Hemodinâmica , Masculino , Norepinefrina/farmacologia , Pressão , Estresse Mecânico , Nicotiana/efeitos dos fármacos
3.
Thorax ; 64(1): 13-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18835959

RESUMO

BACKGROUND: Although exercise training has beneficial effects on skeletal muscle bioenergetics and exercise performance in patients with severe chronic obstructive pulmonary disease (COPD), it may also be associated with increased quadriceps oxidative and nitrosative stress. The aim of this study was to explore quadriceps oxidative and nitrosative stress in patients with severe COPD, both before and after a 3 week endurance exercise programme, and to identify the nature of the oxidatively modified proteins. METHODS: Reactive carbonyls, hydroxynonenal-protein adducts, antioxidant enzymes, nitric oxide synthase (NOS) and 3-nitrotyrosine levels were determined in the quadriceps (pre- and post-exercise) of 15 patients with severe COPD and seven healthy controls using immunoblotting (one- and two-dimensional electrophoresis), activity assays and mass spectrometry. RESULTS: At baseline, muscle levels of reactive carbonyls, which were negatively associated with muscle strength and exercise tolerance, were significantly higher in patients than in controls. Moreover, baseline hydroxynonenal-protein adducts, superoxide dismutase activity, inducible NOS and 3-nitrotyrosine immunoreactivity levels were also significantly increased in the quadriceps of patients compared with controls. In patients, chronic exercise induced a significant rise in inducible NOS levels and a fourfold increase in protein nitration. Chronic endurance exercise induced tyrosine nitration of muscle enolase 3beta, aldolase A, triosephosphate isomerase, creatine kinase, carbonic anhydrase III, myoglobin and uracil DNA glycosylase in the quadriceps of patients, while contractile protein alpha-1 actin was nitrated only in patients exhibiting muscle loss (post hoc analysis). Superoxide dismutase activity increased after the exercise programme only in controls. CONCLUSIONS: In severe COPD, chronic endurance exercise induces increased tyrosine nitration of quadriceps proteins involved in glycolysis, energy distribution, carbon dioxide hydration, muscle oxygen transfer, DNA repair and contractile function in patients exhibiting systemic effects of the disease.


Assuntos
Exercício Físico/fisiologia , Estresse Oxidativo/fisiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Músculo Quadríceps/metabolismo , Tirosina/metabolismo , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/metabolismo , Nitrosação/fisiologia
4.
Eur Respir J ; 31(6): 1205-12, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18287126

RESUMO

Adenosine 5'-monophosphate (AMP) bronchoprovocation reproduces the lung function abnormalities that occur spontaneously during acute asthma and detects peripheral airway inflammation better than direct bronchoconstrictive agents. Pulmonary gas exchange disturbances may reflect changes in small airways related to airway inflammation rather than bronchoconstriction alone. The present authors investigated whether AMP induced a greater imbalance in the ventilation/perfusion ratio than methacholine (MCh), at an equivalent degree of bronchoconstriction, with and without salbutamol pre-medication. In total, 36 asthmatics were studied in three randomised, double-blind, crossover studies: 1) before and after AMP or MCh; 2) before and 30 min after salbutamol or placebo, followed by AMP; or 3) MCh challenge. Sputum was collected before and 4 h post-challenge. Compared with MCh, AMP provoked similar pulmonary gas exchange abnormalities at an equivalent degree of intense bronchoconstriction (forced expiratory volume in one second decrease of 28-44%). While salbutamol blocked AMP- or MCh-induced bronchoconstriction, arterial oxygen tension (P(a,O(2))) and alveolar-arterial oxygen tension difference (P(A-a,O(2))) disturbances induced by AMP and MCh were only partially blocked (P(a,O(2)) by 46 and 42%, respectively; P(A-a,O(2)) by 58 and 57%, respectively). Compared with MCh, AMP increased the percentage of neutrophils (mean+/-se increased from 28+/-4% to 38+/-4%), but this increase did not occur after salbutamol pre-treatment. Both adenosine 5'-monophosphate and methacholine induced similar peripheral airway dysfunction. The fully inhibited adenosine 5'-monophosphate-induced neutrophilia with residual hypoxaemia observed after salbutamol treatment is probably related to beta(2)-agonists acting on both bronchial and pulmonary circulation.


Assuntos
Monofosfato de Adenosina/farmacologia , Asma/tratamento farmacológico , Testes de Provocação Brônquica/métodos , Broncoconstrição/efeitos dos fármacos , Broncoconstritores/farmacologia , Troca Gasosa Pulmonar/efeitos dos fármacos , Agonistas Adrenérgicos beta/uso terapêutico , Adulto , Albuterol/uso terapêutico , Asma/diagnóstico , Asma/fisiopatologia , Estudos de Coortes , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Hipóxia/fisiopatologia , Masculino , Cloreto de Metacolina , Escarro/efeitos dos fármacos , Escarro/imunologia
6.
Sci Total Environ ; 640-641: 874-893, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29879673

RESUMO

In many of the alpine watersheds of Sierra Nevada (Southern Spain) exists an ancient network of dug canals that collect, transport and facilitate the recharge the snowmelt in the underlying aquifer during the spring season. This practice, known as careos, in the lower part of the watersheds supply drinking water as spring discharge during the dry season. To study how this managed recharge technique modifies the natural response of these basins this work focuses on characterizing the hydrological behavior of one of the sites, the Berchules watershed. The mechanisms for mineralization of groundwater are based on geochemical processes such as evapo-concentration in the soil layer and silicate mineral weathering due to dissolved CO2 originated from both soil biogenic processes and the atmosphere. Groundwater presents a main hydrogeochemical calcium­magnesium-bicarbonate type facies, which is associated to groundwater flowing through the upper weathered silicates and quickly drained through springs located in the uplands and in the intermediate altitude catchment zone. Additionally, in the lower part of the basin some springs discharge mineralized groundwater with a sodium-calcium-bicarbonate composition associated to regional groundwater flow. In natural conditions, this hydrogeological system behaves as a sloping aquifer, occurring recharge between 1400 and 2500 m a.s.l. The springs discharge groundwater with an isotopic content and temperature in coherence with the local rainfall isotopic and thermal atmospheric altitudinal lines. Nevertheless, once the careo recharge begins the affected springs reveal the fingerprint of the concentrated recharge system by blurring the fingerprint of both the isotopic and thermal altitudinal dependence in the springs discharge. This validates the previous conceptual model and supports average recharge values of 141 ±â€¯140 mm/yr and total average water resources of 181 ±â€¯111 mm/yr which include a 40% increase in the study period due to the effect of the acequias de careo.

7.
J Clin Invest ; 97(9): 2092-100, 1996 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-8621799

RESUMO

Erythropoietin (rHuEPO) has proven to be effective in the treatment of anemia of chronic renal failure (CRF). Despite improving the quality of life, peak oxygen uptake after rHuEPO therapy is not improved as much as the increase in hemoglobin concentration ([Hb)] would predict. We hypothesized that this discrepancy is due to failure of O2 transport rates to rise in a manner proportional to [Hb]. To test this, eight patients with CRF undergoing regular hemodialysis were studied pre- and post-rHuEPO ([Hb] = 7.5 +/- 1.0 vs. 12.5 +/- 1.0 g x dl-1) using a standard incremental cycle exercise protocol. A group of 12 healthy sedentary subjects of similar age and anthropometric characteristics served as controls. Arterial and femoral venous blood gas data were obtained and coupled with simultaneous measurements of femoral venous blood flow (Qleg) by thermodilution to obtain O2 delivery and oxygen uptake (VO2). Despite a 68% increase in [Hb], peak VO2 increased by only 33%. This could be explained largely by reduced peak leg blood flow, limiting the gain in O2 delivery to 37%. At peak VO2, after rHuEPO, O2 supply limitation of maximal VO2 was found to occur, permitting the calculation of a value for muscle O2 conductance from capillary to mitochondria (DO2). While DO2 was slightly improved after rHuEPO, it was only 67% of that of sedentary control subjects. This kept maximal oxygen extraction at only 70%. Two important conclusions can be reached from this study. First, the increase in [Hb] produced by rHuEPO is accompanied by a significant reduction in peak blood flow to exercising muscle, which limits the gain in oxygen transport. Second, even after restoration of [Hb], O2 conductance from the muscle capillary to the mitochondria remains considerably below normal.


Assuntos
Anemia/tratamento farmacológico , Eritropoetina/uso terapêutico , Falência Renal Crônica/fisiopatologia , Músculo Esquelético/metabolismo , Oxigênio/metabolismo , Adulto , Anemia/complicações , Anemia/metabolismo , Anemia/fisiopatologia , Transporte Biológico/efeitos dos fármacos , Gasometria , Exercício Físico , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/metabolismo , Masculino , Músculo Esquelético/irrigação sanguínea , Consumo de Oxigênio/efeitos dos fármacos
8.
J Clin Invest ; 93(1): 188-94, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8282786

RESUMO

We hypothesized that platelet-activating factor (PAF), a potent inflammatory mediator, could induce gas exchange abnormalities in normal humans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation-perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1 [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased systemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial-alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF, because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04), respectively. We conclude that in normal subjects, inhaled PAF results in considerable immediate VA/Q inequality and gas exchange impairment. These results reinforce the notion that PAF may play a major role as a mediator of inflammation in the human lung.


Assuntos
Fator de Ativação de Plaquetas/análogos & derivados , Fator de Ativação de Plaquetas/farmacologia , Relação Ventilação-Perfusão/efeitos dos fármacos , Adolescente , Adulto , Aerossóis , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Contagem de Leucócitos/efeitos dos fármacos , Masculino , Oxigênio/sangue , Pressão Parcial , Fator de Ativação de Plaquetas/administração & dosagem , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/fisiologia , Fatores de Tempo , Capacidade Vital/efeitos dos fármacos
9.
J Clin Invest ; 97(9): 2101-10, 1996 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-8621800

RESUMO

After erythropoietin (rHuEPO) therapy, patients with chronic renal failure (CRF) do not improve peak O2 uptake (VO2 peak) as much as expected from the rise in hemoglobin concentration ([Hb]). In a companion study, we explain this phenomenon by the concurrent effects of fall in muscle blood flow after rHuEPO and abnormal capillary O2 conductance observed in CRF patients. The latter is likely associated with a poor muscle microcirculatory network and capillary-myofiber dissociation due to uremic myopathy. Herein, cellular bioenergetics and its relationships with muscle O2 transport, before and after rHuEPO therapy, were examined in eight CRF patients (27 +/- 7.3 [SD] yr) studied pre- and post-rHuEPO ([Hb] = 7.8 +/- 0.7 vs. 11.7 +/- 0.7 g x dl-1) during an incremental cycling exercise protocol. Eight healthy sedentary subjects (26 +/- 3.1 yr) served as controls. We hypothesize that uremic myopathy provokes a cytosolic dysfunction but mitochondrial oxidative capacity is not abnormal. 31P-nuclear magnetic resonance spectra (31P-MRS) from the vastus medialis were obtained throughout the exercise protocol consisting of periods of 2 min exercise (at 1.67 Hz) at increasing work-loads interspersed by resting periods of 2.5 min. On a different day, after an identical exercise protocol, arterial and femoral venous blood gas data were obtained together with simultaneous measurements of femoral venous blood flow (Qleg) to calculate O2 delivery (QO2leg) and O2 uptake (VO2leg). Baseline resting [phosphocreatine] to [inorganic phosphate] ratio ([PCr]/[Pi]) did not change after rHuEPO (8.9 +/- 1.2 vs. 8.8 +/- 1.2, respectively), but it was significantly lower than in controls (10.9 +/- 1.5) (P = 0.01 each). At a given submaximal or peak VO2leg, no effects of rHuEPO were seen on cellular bioenergetics ([PCr]/[Pi] ratio, %[PCr] consumption halftime of [PCr] recovery after exercise), nor in intracellular pH (pHi). The post-rHuEPO bioenergetic status and pHi, at a given VO2leg, were below those observed in the control group. However, at a given pHi, no differences in 31P-MRS data were detected between post-rHuEPO and controls. After rHuEPO, at peak VO2, Qleg fell 20% (P < 0.04), limiting the change in QO2leg to 17%, a value that did not reach statistical significance. The corresponding O2 extraction ratio decreased from 73 +/- 4% to 68 +/- 8.2% (P < 0.03). These changes indicate that maximal O2 flow from microcirculation to mitochondria did not increase despite the 50% increase in [Hb] and explain how peak VO2leg and cellular bioenergetics (31P-MRS) did not change after rHuEPO. Differences in pHi, possibly due to lactate differences, between post-rHeEPO and controls appear to be a key factor in the abnormal muscle cell bioenergetics during exercise observed in CRF patients.


Assuntos
Anemia/tratamento farmacológico , Metabolismo Energético/efeitos dos fármacos , Eritropoetina/uso terapêutico , Falência Renal Crônica/metabolismo , Músculo Esquelético/metabolismo , Oxigênio/metabolismo , Adulto , Anemia/complicações , Anemia/metabolismo , Feminino , Humanos , Falência Renal Crônica/complicações , Espectroscopia de Ressonância Magnética , Masculino
10.
Sci Total Environ ; 580: 50-68, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-27960117

RESUMO

In detrital coastal aquifers, seawater and surface water may interact with groundwater in multiple ways. Understanding the interference of water fluxes in this type of environment is essential to effectively manage the groundwater resources in water-stressed regions, such as the Mediterranean coastal fringe. In this research, the characterization of the main hydrogeochemical processes and the interaction between surface water and groundwater in the Marbella-Estepona coastal aquifers (southern Spain) have been carried out by means of the combined use of different hydrogeochemical indicators along with isotope data. The results show that the diversity of source lithologies (peridotite, carbonate and/or metapelitic) substantially conditions the groundwater geochemistry. The analysis of ionic deltas made it possible a preliminary screening of the geochemical reactions that occur in the Marbella-Estepona aquifers, while the Discriminant Analysis allowed for a consistent classification of sampled groundwater types. The dissolution of calcite and dolomite determines the chemical composition of the groundwater from the eastern sector that are more conditioned by the rainwater infiltration. The dissolution of magnesium-bearing minerals (predominantly forming peridotite rocks) is observed in groundwater samples from the western and central sectors, whose chemical composition showed a greater influence of surface water. The spatial analysis of rCl-/Br- in groundwater has permitted to corroborate that saline intrusion is negligible, hardly affecting to its original water quality. The irregularly distributed recharge by precipitation (seasonal effect) and the atmospheric circulation of cloud fronts (coastal/continental effect) explains why most of groundwater sampled is isotopically impoverished with respect to the rainfall signature. The isotope approach also suggests the hydraulic relationship between surface water and groundwater in the study site. A deeper knowledge of spatial hydrogeochemical variations in coastal groundwater and the influence of water sources over them are crucial for a sustainable groundwater management and global change adaptation in equivalent Mediterranean water-stressed regions.

13.
Arch Bronconeumol ; 42(1): 39-41, 2006 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-16426522

RESUMO

Pulmonary varices are uncommon vascular abnormalities that are usually asymptomatic and so they are normally diagnosed by chance from a chest x-ray. They often present as a pulmonary nodule and can be either congenital or acquired. If acquired, they are associated with pulmonary venous hypertension, usually as a result of mitral valve disease. Pulmonary arteriography provides a definitive diagnosis, although the use of new noninvasive imaging techniques is spreading. Treatment is not normally required unless serious complications arise. We present the case of a pulmonary varix located within a pulmonary bulla. This form of presentation has not been previously reported.


Assuntos
Pneumopatias/complicações , Pulmão/irrigação sanguínea , Varizes/complicações , Idoso , Feminino , Humanos , Pneumopatias/diagnóstico por imagem , Radiografia , Varizes/diagnóstico por imagem
14.
Int J Cardiol ; 203: 938-44, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26618257

RESUMO

BACKGROUND: The Spanish "Registry of Pulmonary Arterial Hypertension" (REHAP), started in 2007, includes chronic thromboembolic hypertension (CTEPH) patients. Based on data provided by this registry and retrospective data from patients diagnosed during 2006 (≤ 12 months since the registry was created), clinical management and long-term outcomes of CTEPH patients are analyzed nationwide for the first time in a scenario of a decentralized organization model of CTEPH management. METHODS AND RESULTS: A total of 391 patients (median [Q1:Q3] age 63.7 [48.0;73.3] years, 58% females) with CTEPH included during the period January 1, 2006-December 31, 2013 in the REHAP registry were analyzed. Rate of pulmonary endarterectomy (PEA) was 31.2%, and highly asymmetric among centers: rate was 47.9% at two centers designated as CTEPH expert centers, while it was 4.6% in other centers. Among patients not undergoing PEA, 82% were treated with therapies licensed for pulmonary arterial hypertension (PAH). Five-year survival rate was 86.3% for PEA patients, and 64.9% for non-PEA patients. Among non-PEA patients, presenting proximal lesions (42% of non-referred patients) was associated with a 3-fold increase in mortality. PEA patients achieved significantly better hemodynamic and clinical outcomes at one-year follow-up compared to non-PEA patients. Patients not being referred for PEA assessment were older and had a worse functional capacity. Older age was the most deterrent factor for non-operability. CONCLUSION: Despite the increase in diagnosis and expertise in PEA-specialized centers, an important percentage of patients do not benefit of PEA in a decentralized organization model of CTEPH management.


Assuntos
Gerenciamento Clínico , Endarterectomia/métodos , Hipertensão Pulmonar/etiologia , Embolia Pulmonar/complicações , Sistema de Registros , Doença Crônica , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/terapia , Incidência , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/cirurgia , Estudos Retrospectivos , Espanha/epidemiologia , Taxa de Sobrevida/tendências , Resultado do Tratamento
16.
Chest ; 110(1): 71-7, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8681669

RESUMO

BACKGROUND: The effects of vasoactive drugs, including bronchodilators, on vascular and pulmonary dynamics are interrelated, complex and difficult to measure, but important because of potential deleterious effects on gas exchange. METHODS: To assess the effects of fenoterol at both high and low dose on pulmonary gas exchange in 24 hypoxemic patients with stable COPD: fenoterol, 5 mg; fenoterol, 1 mg and ipratropium bromide, 0.5 mg; ipratropium bromide, 0.5 mg; or matched placebo were nebulized in a double-blind, placebo-controlled fashion. Spirometry, ventilation, systemic hemodynamics, and respiratory and inert gases were measured before and 15, 60, and 120 min after each treatment. RESULTS: Compared with placebo, heart rate (p < 0.002) and cardiac output (p = 0.05) increased after high-dose fenoterol therapy to return to baseline values by 120 min. Following fenoterol at high dose, mean maximum PaO2 change from baseline decreased by 6.3 +/- 1.1 mm Hg (SD) and both alveolararterial oxygen pressure difference (P[A-a]O2), by 8.3 +/- 4.0 mm Hg, and ventilation-perfusion (VA/Q) mismatching increased, as evidenced by increments of the dispersion of pulmonary blood flow, without reaching significance; likewise, low-dose fenoterol therapy increased VA/Q inequalities while both PaO2 and P(A-a)O2 remained unchanged. CONCLUSIONS: In this population of COPD patients, high-dose fenoterol therapy [corrected] significantly increased heart rate and cardiac output resulting in minor adverse consequences on arterial oxygenation and VA/Q relationships.


Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Fenoterol/uso terapêutico , Pneumopatias Obstrutivas/tratamento farmacológico , Relação Ventilação-Perfusão/efeitos dos fármacos , Agonistas Adrenérgicos beta/administração & dosagem , Idoso , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Fenoterol/administração & dosagem , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Ipratrópio/administração & dosagem , Ipratrópio/uso terapêutico , Pneumopatias Obstrutivas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Troca Gasosa Pulmonar/efeitos dos fármacos , Espirometria , Fatores de Tempo
17.
Chest ; 97(2): 268-75, 1990 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2298050

RESUMO

In patients with chronic obstructive pulmonary disease (COPD) studied at rest, nifedipine releases hypoxic pulmonary vasoconstriction (HPV) and worsens gas exchange. During exercise, this drug lowers pulmonary hypertension, but the effects of this lower pulmonary vascular tone on ventilation-perfusion (VA/Q) relationships are still poorly understood. To analyze them, we determined the VA/Q distributions in eight patients with stable COPD (FEV1, 36 percent of predicted) at rest and during exercise (60 percent VO2 max), before and after nifedipine (20 mg sublingually). Nifedipine shifted to the right the pulmonary pressure-flow relationship (p less than 0.01) and increased the dispersion of the blood flow distribution at rest and during exercise (p less than 0.005). These observations strongly suggest that nifedipine released HPV under both conditions. However, even after releasing HPV by nifedipine, exercise distributed blood flow more homogeneously than at rest (p less than 0.05). Besides, exercise greatly decreased the overall degree of VA/Q mismatching (p less than 0.001) not only before but also after nifedipine. Thus, we postulate that most of the VA/Q improvement that exercise may induce in patients with COPD, as it is shown here, is due to improvement in the ventilation distribution. Interestingly, this VA/Q improvement was not paralleled by a significant decrease of P(A-a)O2. This apparent paradox could be explained by 20 percent of the actual P(A-a)O2 during exercise due to diffusion limitation, as assessed through the inert gas approach. Taken all together, these results help to better understand the mechanisms that govern pulmonary gas exchange during exercise in COPD.


Assuntos
Exercício Físico/fisiologia , Pneumopatias Obstrutivas/fisiopatologia , Nifedipino/farmacologia , Circulação Pulmonar/fisiologia , Teste de Esforço , Humanos , Pneumopatias Obstrutivas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Circulação Pulmonar/efeitos dos fármacos , Descanso/fisiologia , Relação Ventilação-Perfusão/fisiologia
18.
Chest ; 120(3): 852-9, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11555520

RESUMO

STUDY OBJECTIVES: To evaluate the intraoperative evolution of patients with COPD during lung resection and to test whether exercise testing could be helpful in the prediction of the intraoperative course. DESIGN: Prospective study. SETTING: University teaching hospital. PATIENTS: Forty patients (mean [+/- SD] age, 65 +/- 9 years) with COPD (ie, FEV(1), 55 +/- 11% of predicted) and resectable lung neoplasms. INTERVENTIONS: Preoperatively, pulmonary function testing, quantitative lung perfusion scanning, and exercise performance testing were administered. Intraoperatively, pulmonary, hemodynamic, and blood gas measurements were performed at five stages, including periods of two-lung ventilation (TLV) and periods of one-lung ventilation (OLV). RESULTS: During OLV, compared with TLV, the PaO(2)/fraction of inspired oxygen (FIO(2)) ratio decreased from 458 +/- 120 to 248 +/- 131 mm Hg (p < 0.05), whereas pulmonary artery pressure (PAP) increased from 18 +/- 5 to 23 +/- 5 mm Hg (p < 0.05). Cardiac output (t) also increased from 4.0 +/- 1.2 to 5.1 +/- 1.9 L/min (p < 0.05), yielding to a higher mixed venous PO(2). Both PaO(2) and t during OLV were significantly lower in patients who had undergone right thoracotomies compared with those who had undergone left thoracotomies. The PaO(2)/FIO(2) ratio during OLV correlated with the PaO(2) during exercise (r = 0.39; p = 0.01) and with the perfusion of the non-neoplastic lung (r = 0.44; p = 0.005). CONCLUSIONS: In COPD patients, OLV leads to a significant derangement of gas exchange, which is more pronounced in right thoracotomies. Preoperative measurement of PaO(2) during exercise and the distribution of perfusion by lung scan might be useful to identify those patients who are at the greatest risk of abnormal gas exchange during lung resections.


Assuntos
Pneumopatias Obstrutivas/etiologia , Pneumopatias Obstrutivas/fisiopatologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Troca Gasosa Pulmonar , Mecânica Respiratória , Idoso , Contraindicações , Teste de Esforço , Feminino , Hemodinâmica , Humanos , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Toracotomia
19.
Pediatr Infect Dis J ; 6(1): 24-8, 1987 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3103090

RESUMO

We reviewed the charts of 59 pediatric and adult patients hospitalized because of animal bites (46 dog bites, 10 cat bites, 3 monkey bites). The bites of 40 of the 59 patients were infected at the time of admission. Gram-stained specimens correctly predicted the infecting bacteria in only 5 of 20 cases. Eighty-three percent of the bacterial isolates were penicillin-susceptible. Before admission 14 patients had received outpatient antibiotic prophylaxis and the infections in 11 of these 14 patients were caused by bacteria susceptible to the prophylactic antibiotic. Complications were more common if antimicrobial therapy had not been altered according to susceptibility testing results. Of the 59 patients 19 were admitted immediately after being bitten because of severe uninfected bites. Of these 19 patients 18 received prophylactic antibiotics and none developed a serious complication.


Assuntos
Mordeduras e Picadas/complicações , Gatos , Cães , Haplorrinos , Infecção dos Ferimentos/etiologia , Animais , Mordeduras e Picadas/tratamento farmacológico , Mordeduras e Picadas/cirurgia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/prevenção & controle
20.
J Appl Physiol (1985) ; 77(4): 2018-22, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7836231

RESUMO

To examine whether the tip of the femoral vein catheter used for sampling femoral venous PO2 during cycling exercise is contaminated by skin or saphenous vein blood, we studied 6 healthy volunteers [21.7 +/- 0.7 (SD) yr] during three identical incremental exercise tests while breathing room air on the same day. Femoral venous blood was sampled simultaneously from two catheters inserted into the femoral vein but advanced in opposite directions (7 cm distally and 5 cm proximally). Blood sampling for measurements of PO2, PCO2, pH, hemoglobin concentration, and oxyhemoglobin saturation was done simultaneously from both catheters in duplicate at rest, at 60% of maximum workload (60% W), and at maximum symptom-limited exercise (100% W). Temperature was measured with a thermistor probe placed in the proximal catheter. At rest, distal PO2 was significantly lower than that measured proximally (24.9 +/- 4.3 vs 30.8 +/- 6.1 mmHg, respectively; P < 0.004), but no differences were found during exercise (60% W, 23.6 +/- 3.4 vs. 24.5 +/- 3.6 mmHg; 100% W, 26.0 +/- 3.6 vs. 25.5 +/- 2.8 mmHg, respectively). Comparison of blood temperatures between proximal and distal sites of sampling in two subjects showed negligible differences. Intrasubject coefficient of variation of distal femoral venous PO2 over the three bouts of exercise was 11.5% (2.9 mmHg) at rest, 5.9% (1.4 mmHg) at 60% W, and 5.6% (1.5 mmHg) at 100% W. Mean differences in distal PO2 between duplicate samples were 0.5 +/- 1.4 mmHg at rest, 0.1 +/- 0.8 mmHg at 60% W, and 0.6 +/- 0.9 mmHg at 100% W.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Gasometria , Dióxido de Carbono/sangue , Veia Femoral , Oxigênio/sangue , Adulto , Coleta de Amostras Sanguíneas , Cateterismo Periférico , Exercício Físico , Feminino , Humanos , Masculino , Consumo de Oxigênio , Temperatura
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA