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1.
J Physiol ; 597(22): 5365-5384, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31429918

RESUMO

KEY POINTS: Imaging techniques such as contrast echocardiography suggest that anatomical intra-pulmonary arteriovenous anastomoses (IPAVAs) are present at rest and are recruited to a greater extent in conditions such as exercise. IPAVAs have the potential to act as a shunt, although gas exchange methods have not demonstrated significant shunt in the normal lung. To evaluate this discrepancy, we compared anatomical shunt with 25-µm microspheres to contrast echocardiography, and gas exchange shunt measured by the multiple inert gas elimination technique (MIGET). Intra-pulmonary shunt measured by 25-µm microspheres was not significantly different from gas exchange shunt determined by MIGET, suggesting that MIGET does not underestimate the gas exchange consequences of anatomical shunt. A positive agitated saline contrast echocardiography score was associated with anatomical shunt measured by microspheres. Agitated saline contrast echocardiography had high sensitivity but low specificity to detect a ≥1% anatomical shunt, frequently detecting small shunts inconsequential for gas exchange. ABSTRACT: The echocardiographic visualization of transpulmonary agitated saline microbubbles suggests that anatomical intra-pulmonary arteriovenous anastomoses are recruited during exercise, in hypoxia, and when cardiac output is increased pharmacologically. However, the multiple inert gas elimination technique (MIGET) shows insignificant right-to-left gas exchange shunt in normal humans and canines. To evaluate this discrepancy, we measured anatomical shunt with 25-µm microspheres and compared the results to contrast echocardiography and MIGET-determined gas exchange shunt in nine anaesthetized, ventilated canines. Data were acquired under the following conditions: (1) at baseline, (2) 2 µg kg-1  min-1 i.v. dopamine, (3) 10 µg kg-1  min-1 i.v. dobutamine, and (4) following creation of an intra-atrial shunt (in four animals). Right to left anatomical shunt was quantified by the number of 25-µm microspheres recovered in systemic arterial blood. Ventilation-perfusion mismatch and gas exchange shunt were quantified by MIGET and cardiac output by direct Fick. Left ventricular contrast scores were assessed by agitated saline bubble counts, and separately by appearance of 25-µm microspheres. Across all conditions, anatomical shunt measured by 25-µm microspheres was not different from gas exchange shunt measured by MIGET (microspheres: 2.3 ± 7.4%; MIGET: 2.6 ± 6.1%, P = 0.64). Saline contrast bubble score was associated with microsphere shunt (ρ = 0.60, P < 0.001). Agitated saline contrast score had high sensitivity (100%) to detect a ≥1% shunt, but low specificity (22-48%). Gas exchange shunt by MIGET does not underestimate anatomical shunt measured using 25-µm microspheres. Contrast echocardiography is extremely sensitive, but not specific, often detecting small anatomical shunts which are inconsequential for gas exchange.


Assuntos
Anastomose Arteriovenosa/fisiologia , Troca Gasosa Pulmonar/fisiologia , Animais , Anastomose Arteriovenosa/metabolismo , Cães , Ecocardiografia/métodos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Pulmão/metabolismo , Pulmão/fisiologia , Microesferas , Oxigênio/metabolismo , Circulação Pulmonar/fisiologia , Respiração , Relação Ventilação-Perfusão/fisiologia
2.
J Physiol ; 597(22): 5385-5397, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31448407

RESUMO

KEY POINTS: Precapillary gas exchange for oxygen has been documented in both humans and animals. It has been suggested that, if precapillary gas exchange occurs to a greater extent for inert gases than for oxygen, shunt and its effects on arterial oxygenation may be underestimated by the multiple inert gas elimination technique (MIGET). We evaluated fractional precapillary gas exchange in canines for O2 and two inert gases, sulphur hexafluoride and ethane, by measuring these gases in the proximal pulmonary artery, distal pulmonary artery (1 cm proximal to the wedge position) and systemic artery. Some 12-19% of pulmonary gas exchange occurred within small (1.7 mm in diameter or larger) pulmonary arteries and this was quantitatively similar for oxygen, sulphur hexafluoride and ethane. Under these experimental conditions, this suggests only minor effects of precapillary gas exchange on the magnitude of calculated shunt and the associated effect on pulmonary gas exchange estimated by MIGET. ABSTRACT: Some pulmonary gas exchange is known to occur proximal to the pulmonary capillary, although the magnitude of this gas exchange is uncertain, and it is unclear whether oxygen and inert gases are similarly affected. This has implications for measuring shunt and associated gas exchange consequences. By measuring respiratory and inert gas levels in the proximal pulmonary artery (P), a distal pulmonary artery 1 cm proximal to the wedge position (using a 5-F catheter) (D) and a systemic artery (A), we evaluated precapillary gas exchange in 27 paired samples from seven anaesthetized, ventilated canines. Fractional precapillary gas exchange (F) was quantified for each gas as F = (P - D)/(P - A). The lowest solubility inert gases, sulphur hexafluoride (SF6 ) and ethane were used because, with higher solubility gases, the P-A difference is sufficiently small that experimental error prevents accurate assessment of F. Distal samples (n = 12) with oxygen (O2 ) saturation values that were (within experimental error) equal to or above systemic arterial values, suggestive of retrograde capillary blood aspiration, were discarded, leaving 15 for analysis. D was significantly lower than P for SF6 (D/P = 88.6 ± 18.1%; P = 0.03) and ethane (D/P = 90.6 ± 16.0%; P = 0.04), indicating partial excretion of inert gas across small pulmonary arteries. Distal pulmonary arterial O2 saturation was significantly higher than proximal (74.1 ± 6.8% vs. 69.0 ± 4.9%; P = 0.03). Fractional precapillary gas exchange was similar for SF6 , ethane and O2 (0.12 ± 0.19, 0.12 ± 0.20 and 0.19 ± 0.26, respectively; P = 0.54). Under these experimental conditions, 12-19% of pulmonary gas exchange occurs within the small pulmonary arteries and the extent is similar between oxygen and inert gases.


Assuntos
Pulmão/metabolismo , Pulmão/fisiologia , Gases Nobres/metabolismo , Oxigênio/metabolismo , Troca Gasosa Pulmonar/fisiologia , Animais , Cães , Circulação Pulmonar/fisiologia
3.
Respir Med ; 155: 133-140, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31349187

RESUMO

BACKGROUND: Asthmatics are at increased cardiovascular disease risk, which has been linked to beta2(ß2)-agonist use. Inhalation of ß2-agonists increases sympathetic nerve activity (SNA) in healthy individuals, however the systemic impact of salbutamol in asthmatics using ß2-agonists regularly is unknown. OBJECTIVES: This study compared the systemic vascular responses to a clinical dose of salbutamol (Phase I) and following an acute increase in SNA (Phase II) in asthmatics and controls. METHODS: Fourteen controls and 14 asthmatics were recruited for Phase I. On separate days, flow-mediated dilation (FMD) and peripheral arterial stiffness (pPWV) were evaluated at baseline and following either 400 µg inhaled salbutamol or a placebo inhaler. For Phase II, heart rate, blood pressure, vascular conductance, pPWV, and central (c)PWV were evaluated in response to a large increase in SNA brought on by cold-water hand immersion (i.e. cold-pressor test) or body-temperature water hand immersion (i.e. control) in 10 controls and 10 asthmatics. RESULTS: Following salbutamol, asthmatics demonstrated reduced FMD (-3.0%, p < 0.05) and increased pPWV (+0.7 m/s, p < 0.05); however, salbutamol had no effect in controls. The cold-pressor test resulted in similar increases in blood pressure, vascular flow rates and conductance, pPWV, and cPWV in both asthmatics and controls, suggesting similar neurovascular transduction in asthmatics and controls. CONCLUSION: Inhaled Salbutamol leads to increased arterial stiffness and reduced FMD in asthmatics. As asthmatics and controls had similar vascular responses to an increase in SNA, these findings suggest asthmatics have heightened sympathetic responses to ß2-agonists which may contribute to the increased cardiovascular risk in asthma.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Albuterol/administração & dosagem , Asma/tratamento farmacológico , Asma/fisiopatologia , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Adulto , Albuterol/efeitos adversos , Pressão Sanguínea , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Masculino , Risco , Rigidez Vascular , Adulto Jovem
4.
J Appl Physiol (1985) ; 127(5): 1278-1287, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31295067

RESUMO

Recent work demonstrates that carotid chemoreceptor (CC) activity/sensitivity is elevated in patients with chronic obstructive pulmonary disease (COPD) compared with healthy controls, and this elevated chemoreception appears to contribute to increased cardiovascular risk. Exercise training has been shown to normalize CC activity/sensitivity in other populations, and therefore, the purpose of this study was to determine whether pulmonary rehabilitation (PR) can reduce CC activity/sensitivity in COPD. Forty-five COPD patients [mean FEV1 (forced expiratory volume in 1 s) = 56.6% predicted] completed PR, while 15 COPD patients (mean FEV1 = 74.6% predicted) served as non-PR controls. CC activity was determined by the reduction in ventilation while breathing transient hyperoxia ([Formula: see text] = 1.0); CC sensitivity was evaluated by the increase in ventilation relative to the drop in arterial saturation while breathing hypoxia. Dyspnea, six-minute walk and autonomic function data were also obtained. PR improved 6-minute walk distance (P < 0.001) and dyspnea (P = 0.04); however, there was no effect on CC activity (P = 0.60), sensitivity (P = 0.69), or autonomic function (P > 0.05 for all). Subgroup analyses indicated that PR reduced CC activity in those with elevated baseline CC activity, independent of changes in autonomic function. No change in dyspnea (P = 0.24), CC activity (P = 0.19), sensitivity (P = 0.80), or autonomic function (P > 0.05 for all) was observed in the control group. Despite improvements in exercise tolerance and dyspnea, PR appears to be generally ineffective at reducing CC sensitivity in stable COPD patients; while PR reduced CC activity in those with elevated basal CC activity, the physiological significance of this is unclear. Further investigations aimed at improving CC function in COPD are needed.NEW & NOTEWORTHY While work in other chronic diseases has shown that exercise training may help normalize carotid chemoreceptor (CC) activity/sensitivity, the current study found that exercise training through pulmonary rehabilitation did not consistently reduce CC activity/sensitivity in patients with chronic obstructive pulmonary disease (COPD). These results suggest that other interventions are needed to normalize CC activity/sensitivity in COPD.


Assuntos
Corpo Carotídeo/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Idoso , Estudos de Casos e Controles , Dispneia/fisiopatologia , Humanos , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
5.
J Cardiopulm Rehabil Prev ; 38(5): 320-326, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29652760

RESUMO

PURPOSE: Some patients with chronic obstructive pulmonary disease (COPD) fail to achieve health benefits with pulmonary rehabilitation (PR). Exercise intensity and load represent stimulus for adaptation but it is unclear whether inappropriate exercise intensity and/or load are affected by severity of COPD, which may affect health benefits. The purpose was to determine whether COPD severity and/or the severity of pulmonary limitation to exercise (PLE) impacted exercising intensity or load and whether resultant intensity/load affected health outcomes derived from PR. METHODS: Patients with COPD (n = 58, age = 67 ± 7 y, forced expiratory volume in the first second of expiration [FEV1] % predicted = 52 ± 21%) were recruited upon referral to PR. Primary health outcomes evaluated were 6-min walk distance and St George's Respiratory Questionnaire. Patients were stratified for disease severity using Global Initiative for Obstructive Lung Disease (GOLD) staging and PLE severity by change in inspiratory capacity during exercise. Exercise intensity and load were calculated from daily exercise records. RESULTS: Participants achieved comparable training duration and load regardless of GOLD severity. Patients with more severe PLE achieved greater training duration (more severe: 546 ± 143 min., less severe: 451 ± 109 min., P = .036), and relative training load (more severe: 2200.8 ± 595.3 kcal, less severe: 1648.3 ± 597.8 kcal, P = .007). Greater overall training load was associated with greater improvements in 6-min walk distance (r = 0.24, P = .035). No significant relationships were observed between PLE, GOLD severity, training parameters, and St George's Respiratory Questionnaire response. CONCLUSIONS: Improvements in exercise tolerance can be explained by achieving greater training loads, demonstrating the importance of appropriate training load to maximize health outcomes in PR.


Assuntos
Terapia por Exercício/métodos , Exercício Físico/fisiologia , Esforço Físico/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Idoso , Volume Expiratório Forçado , Humanos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e Questionários , Teste de Caminhada
6.
Respir Med ; 132: 56-61, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29229106

RESUMO

BACKGROUND: Heightened arterial stiffness is a marker of cardiovascular risk and is elevated in chronic obstructive pulmonary disease (COPD). Physical activity has been shown to reduce arterial stiffness, and our previous work has shown that arterial stiffness is related to physical activity and exercise tolerance in COPD. The purpose of this study was to evaluate whether baseline physical activity and exercise tolerance influence the cardiovascular benefits associated with standard COPD outpatient pulmonary rehabilitation (PR). METHODS: A total of 66 patients with COPD were recruited from the G.F. MacDonald Centre for Lung Health, Edmonton, Alberta, prior to entering PR. Another 23 COPD patients not attending the PR program were recruited as time controls (TC). Arterial stiffness (carotid-radial pulse wave velocity, PWV), physical activity (steps taken over three days), and 6-min walk distance (6MWD) were assessed before and after PR, or before and after six weeks of standard care. RESULTS: Thirty-nine PR and 11 TC completed all parts of the study. Following PR, there was no overall change in PWV. However, changes in arterial stiffness with PR were dependent on baseline exercise tolerance, with those patients with a 6MWD <350 m showing a significant reduction in PWV following PR (6MWD >350 m: 8.2 ± 1.6 to 8.5 ± 1.7 versus 6MWD <350 m: 9.2 ± 0.6 to 7.3 ± 2.0 m/s, p < 0.05). The PWV response to PR was not influenced by baseline physical activity levels. CONCLUSION: COPD patients with low exercise tolerance appear to derive the greatest cardiovascular benefits from PR.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Tolerância ao Exercício/fisiologia , Exercício Físico , Doença Pulmonar Obstrutiva Crônica/reabilitação , Rigidez Vascular/fisiologia , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Terapia por Exercício/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Análise de Onda de Pulso , Terapia Respiratória/métodos , Teste de Caminhada
7.
Respir Physiol Neurobiol ; 231: 14-20, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27236040

RESUMO

Asthma independently increases the risk of developing cardiovascular disease. As inhaled ß-agonists have systemic cardiovascular effects, and elevations in arterial stiffness and sympathetic nerve activity are associated with increased cardiovascular morbidity/mortality, this study examines the effect of salbutamol use on pulse wave velocity (PWV) and muscle sympathetic nervous activity (MSNA). Healthy men and women (26.2±1.5years) were recruited for: Day 1: 4 inhalations of placebo followed by 4 inhalations of salbutamol (4×100µg); Day 2: placebo only; Day 3: carotid-femoral PWV measurements before/after placebo/salbutamol. Heart rate (HR), mean arterial pressure (MAP), and carotid-radial PWV were obtained on Day 1 and 2. MSNA was obtained on Day 1. Salbutamol increased HR and total MSNA (Baseline1: 2.8±2.8au; Placebo: 2.4±2.1au; Baseline2: 2.7±3.0au; Salbutamol: 3.3±2.9au; p=0.05), with no changes in MAP or PWV. There were no effects of placebo on HR, MSNA, or PWV. Acute salbutamol use increases sympathetic activity suggesting that salbutamol could contribute to cardiovascular morbidity/mortality in individuals using inhaled ß-agonists.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Albuterol/administração & dosagem , Sistema Nervoso Simpático/efeitos dos fármacos , Rigidez Vascular/efeitos dos fármacos , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Adulto , Albuterol/efeitos adversos , Pressão Arterial/efeitos dos fármacos , Doenças Cardiovasculares/epidemiologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Análise de Onda de Pulso , Risco , Adulto Jovem
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