Effects of increasing tidal volume and end-expiratory lung volume on induced bronchoconstriction in healthy humans.

BACKGROUND: Increasing functional residual capacity (FRC) or tidal volume (VT) reduces airway resistance and attenuates the response to bronchoconstrictor stimuli in animals and humans. What is unknown is which one of the above mechanisms is more effective in modulating airway caliber and whether their combination yields additive or synergistic effects. To address this question, we investigated the effects of increased FRC and increased VT in attenuating the bronchoconstriction induced by inhaled methacholine (MCh) in healthy humans. METHODS: Nineteen healthy volunteers were challenged with a single-dose of MCh and forced oscillation was used to measure inspiratory resistance at 5 and 19 Hz (R5 and R19), their difference (R5-19), and reactance at 5 Hz (X5) during spontaneous breathing and during imposed breathing patterns with increased FRC, or VT, or both. Importantly, in our experimental design we held the product of VT and breathing frequency (BF), i.e, minute ventilation (VE) fixed so as to better isolate the effects of changes in VT alone. RESULTS: Tripling VT from baseline FRC significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Doubling VT while halving BF had insignificant effects. Increasing FRC by either one or two VT significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Increasing both VT and FRC had additive effects on R5, R19, R5-19 and X5, but the effect of increasing FRC was more consistent than increasing VT thus suggesting larger bronchodilation. When compared at iso-volume, there were no differences among breathing patterns with the exception of when VT was three times larger than during spontaneous breathing. CONCLUSIONS: These data show that increasing FRC and VT can attenuate induced bronchoconstriction in healthy humans by additive effects that are mainly related to an increase of mean operational lung volume. We suggest that static stretching as with increasing FRC is more effective than tidal stretching at constant VE, possibly through a combination of effects on airway geometry and airway smooth muscle dynamics.

Respiratory Responses to Single Oral Administration of Taurine in Sprague-Dawley Rats.

Taurine is a nonessential amino acid that has been increasingly consumed due to its various beneficial biological effects. Excessive taurine intake has been linked to the positive regulation of inflammatory responses and endoplasmic reticulum stress through the modulation of intracellular calcium levels. However, research on the potential adverse effects of taurine consumption on the respiratory system is limited. To address this, we investigated the respiratory responses of 6-week-old male Sprague-Dawley rats to taurine administered orally at 0, 100, 200, and 400 mg/kg. Respiratory rate, tidal volume, and minute volume were monitored in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Harmonized Tripartite Guideline S7A for Safety Pharmacology Studies for Human Pharmaceuticals. We found that taurine administration did not significantly alter respiratory rate or tidal volume; however, a significant increase in minute volume was observed 6 h after administration of 200 mg/kg taurine.

Tidal expiratory flow limitation during exercise is unrelated to peripheral hypercapnic chemosensitivity.

We sought to determine if peripheral hypercapnic chemosensitivity is related to expiratory flow limitation (EFL) during exercise. Twenty participants completed one testing day which consisted of peripheral hypercapnic chemosensitivity testing and a maximal exercise test to exhaustion. The chemosensitivity testing consisting of two breaths of 10% CO2 (O2∼21%) repeated 5 times during seated rest and the first 2 exercise intensities during the maximal exercise test. Following chemosensitivity testing, participants continued cycling with the intensity increasing 20 W every 1.5 minutes till exhaustion. Maximal expiratory flow-volume curves were derived from forced expiratory capacity maneuvers performed before and after exercise at varying efforts. Inspiratory capacity maneuvers were performed during each exercise stage to determine EFL. There was no difference between the EFL and non-EFL hypercapnic chemoresponse (mean response during exercise 0.96 ± 0.46 and 0.91 ± 0.33 l min-1 mmHg-1, p=0.783). Peripheral hypercapnic chemosensitivity during mild exercise does not appear to be related to the development of EFL during exercise.

Effect of chronic ethanol exposure on rat ventilatory responses to hypoxia and hypercapnia

OBJECTIVE: The effect of chronic ethanol exposure on chemoreflexes has not been extensively studied in experimental animals. Therefore, this study tested the hypothesis that known ethanol-induced autonomic, neuroendocrine and cardiovascular changes coincide with increased chemoreflex sensitivity, as indicated by increased ventilatory responses to hypoxia and hypercapnia. METHODS: Male Wistar rats were subjected to increasing ethanol concentrations in their drinking water (first week: 5% v/v, second week: 10% v/v, third and fourth weeks: 20% v/v). At the end of each week of ethanol exposure, ventilatory parameters were measured under basal conditions and in response to hypoxia (evaluation of peripheral chemoreflex sensitivity) and hypercapnia (evaluation of central chemoreflex sensitivity). RESULTS: Decreased respiratory frequency was observed in rats exposed to ethanol from the first until the fourth week, whereas minute ventilation remained unchanged. Moreover, we observed an increased tidal volume in the second through the fourth week of exposure. The minute ventilation responses to hypoxia were attenuated in the first through the third week but remained unchanged during the last week. The respiratory frequency responses to hypoxia in ethanol-exposed rats were attenuated in the second through the third week but remained unchanged in the first and fourth weeks. There was no significant change in tidal volume responses to hypoxia. With regard to hypercapnic responses, no significant changes in ventilatory parameters were observed. CONCLUSIONS: Our data are consistent with the notion that chronic ethanol exposure does not increase peripheral or central chemoreflex sensitivity. .

The effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients

OBJECTIVE: The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients. METHODS: Twenty male chronic obstructive pulmonary disease patients (66.2 + 8.3 years old, FEV1: 49.3+19.8%) received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. ClinicalTrials.gov: NCT00500864 RESULTS: Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l) and residual volume (-0.47 l), the mean arterial blood pressure (-5.6 mmHg) and the cardiac double product (734.8 mmHg.bpm) at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w) and the respiratory exchange ratio (0.06) at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l). CONCLUSIONS: The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding.

Capnografia volumétrica na identificação da não homogeneidade da ventilação em crianças e adolescentes com asma persistente controlada / Volumetric capnography to detect ventilation inhomogeneity in children and adolescents with controlled persistent asthma

OBJETIVOS: Estudar alterações nas variáveis de capnografia volumétrica em crianças e adolescentes asmáticos comparados com grupo-controle e investigar suas mudanças com o uso do broncodilatador e do teste de broncoprovocação com metacolina. MÉTODOS: Cento e três pacientes com asma persistente controlada e 40 voluntários saudáveis participaram do estudo. Todos realizaram exames de capnografia volumétrica e espirometria. Todos os asmáticos repetiram os exames após uso do broncodilatador. Dos 103 asmáticos, 33 realizaram teste de broncoprovocação com metacolina, e foram registradas as medidas em três momentos: antes e após metacolina e após broncodilatador. RESULTADOS: Comparados ao grupo-controle, os asmáticos apresentaram aumento do slope da fase III normalizado pelo volume corrente e diminuição do volume corrente, do volume expiratório forçado no primeiro segundo, da capacidade vital forçada, do índice de obstrução e do fluxo expiratório forçado entre 25 a 75 por cento da capacidade vital forçada. Após o broncodilatador, houve aumento das variáveis espirométricas, do volume espaço morto anatômico e diminuição do slope da fase II normalizado pelo volume corrente; porém não houve alteração do slope da fase III normalizado pelo volume corrente. Após a metacolina, houve aumento dessa variável, com diminuição após broncodilatador. CONCLUSÕES: O aumento do slope da fase III normalizado pelo volume corrente nos pacientes asmáticos sugere que eles apresentam uma não homogeneidade da ventilação nos espaços aéreos distais, podendo refletir tanto distúrbios estruturais crônicos de vias aéreas como alterações agudas reversíveis observadas no teste de broncoprovocação.

OBJECTIVES: To study changes in the variables of volumetric capnography in children and adolescents with asthma compared with a control group and to investigate their changes with the use of bronchodilators and bronchial provocation test with methacholine. METHODS: One hundred and three patients with controlled persistent asthma and 40 healthy volunteers participated in the study. All of them underwent volumetric capnography and spirometry. All asthmatics repeated the tests after bronchodilator use. Among 103 asthma patients, 33 underwent methacholine challenge test, and measures were recorded on three occasions: before and after methacholine and after bronchodilator use. RESULTS: Compared with the control group, asthmatics had an increase in the slope of phase III normalized by tidal volume and decreases in tidal volume, forced expiratory volume in one second, forced vital capacity, rate of obstruction and forced expiratory flow between 25 to 75 percent of forced vital capacity. After bronchodilator use, there was an increase in spirometric variables, volume of anatomic dead space, and decrease in the slope of phase II normalized by tidal volume, but the slope of phase III normalized by tidal volume did not change. After methacholine, there was an increase in this variable, which decreased after bronchodilator use. CONCLUSIONS: The increase in the slope of phase III normalized by tidal volume in asthma patients suggests that these patients have ventilation inhomogeneity in the distal air spaces, which may reflect chronic structural disorders or reversible acute changes seen on the bronchial provocation test.

Thoracic sympathetic block reduces respiratory system compliance

CONTEXT AND OBJECTIVE: Thoracic epidural anesthesia (TEA) following thoracic surgery presents known analgesic and respiratory benefits. However, intraoperative thoracic sympathetic block may trigger airway hyperreactivity. This study weighed up these beneficial and undesirable effects on intraoperative respiratory mechanics. DESIGN AND SETTING: Randomized, double-blind clinical study at a tertiary public hospital. METHODS: Nineteen patients scheduled for partial lung resection were distributed using a random number table into groups receiving active TEA (15 ml 0.5 percent bupivacaine, n = 9) or placebo (15 ml 0.9 percent saline, n = 10) solutions that also contained 1:200,000 epinephrine and 2 mg morphine. Under general anesthesia, flows and airway and esophageal pressures were recorded. Pressure-volume curves, lower inflection points (LIP), resistance and compliance at 10 ml/kg tidal volume were established for respiratory system, chest wall and lungs. StudentÆs t test was performed, including confidence intervals (CI). RESULTS: Bupivacaine rose 5 ± 1 dermatomes upwards and 6 ± 1 downwards. LIP was higher in the bupivacaine group (6.2 ± 2.3 versus 3.6 ± 0.6 cmH2O, p = 0.016, CI = -3.4 to -1.8). Respiratory system and lung compliance were higher in the placebo group (respectively 73.3 ± 10.6 versus 51.9 ± 15.5, p = 0.003, CI = 19.1 to 23.7; 127.2 ± 31.7 versus 70.2 ± 23.1 ml/cmH2O, p < 0.001, CI = 61 to 53). Resistance and chest wall compliance showed no difference. CONCLUSION: TEA decreased respiratory system compliance by reducing its lung component. Resistance was unaffected. Under TEA, positive end-expiratory pressure and recruitment maneuvers are advisable.

CONTEXTO E OBJETIVO: Os benefícios pós-operatórios da anestesia peridural torácica (APT) na analgesia e respiração após toracotomias são conhecidos. Contudo, bloqueio simpático torácico pode desencadear hiperreatividade das vias aéreas. Este estudo pesou tais efeitos benéficos e indesejáveis na mecânica respiratória intra-operatória. TIPO DE ESTUDO E LOCAL: Estudo clínico, randomizado, duplo-cego realizado em hospital público terciário. MÉTODOS: Uma tabela de números aleatórios dividiu 19 pacientes submetidos a ressecção pulmonar parcial entre duas soluções administradas na APT: ativa (15 ml 0,5 por cento bupivacaína, n = 9) ou placebo (15 ml 0,9 por cento NaCl, n = 10). Ambas continham epinefrina 1:200,000 e morfina 2 mg. Sob anestesia geral, pressões esofágicas e de vias aéreas foram registradas. Curvas de pressão versus volume, pontos de inflexão inferior (PII), resistências e complacências sob volume corrente de 10 ml.kg-1 foram aferidos para sistema respiratório, parede torácica e pulmões. O teste t de Student foi realizado (p < 0,005), incluindo intervalos de confiança (IC). RESULTADOS: A dispersão cefálica e caudal da bupivacaína foi, respectivamente, de 5 ± 1 e de 6 ± 1 dermátomos. A curva PII foi maior no Grupo Bupivacaína (6,2 ± 2,3 versus 3,6 ± 0,6 cm H2O, p = 0,016, IC = -3,4 a -1,8). Complacências do sistema respiratório e pulmões foram maiores no Grupo Placebo (respectivamente 73.3 ± 10.6 versus 51.9 ± 15.5, p = 0,003, IC = 19,1 a 23,7, e 127,2 ± 31,7 versus 70,2 ± 23,1 ml.cm H2O-1, p < 0,001, IC = 61 a 53). Resistências e complacências da parede torácica não mostraram diferenças. CONCLUSÃO: APT diminui a complacência do sistema respiratório por reduzir seu componente pulmonar. Resistências não são afetadas. Sob APT, pressão positiva expiratória final e manobras de recrutamento são recomendáveis.