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BACKGROUND: Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. METHODS: This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. RESULTS: Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs. CONCLUSION: In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden.
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Modelos Animais de Doenças , Embolia Pulmonar , Resistência Vascular , Animais , Embolia Pulmonar/fisiopatologia , Suínos , Resistência Vascular/fisiologia , Distribuição Aleatória , Gasometria , Função Ventricular Direita/fisiologia , Disfunção Ventricular Direita/fisiopatologia , Feminino , MasculinoRESUMO
BACKGROUND: Pulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism. METHODS: Anesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO2 concentration (ETCO2), shape factors, and dead space parameters by volumetric capnography. RESULTS: In the presence of a uniform decrease in ETCO2 in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO2, and PaCO2, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting. CONCLUSIONS: Our findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO2 elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.
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Embolia Aérea , Embolia Pulmonar , Tromboembolia , Animais , Ratos , Dióxido de Carbono , Hipocapnia , Perfusão , Brônquios , BroncoconstriçãoRESUMO
OBJECTIVE: To study the changes in dynamic compliance (Cdyn), ventilation/perfusion (VË/ QË) mismatch and haemodynamic variables in hypoxaemic anaesthetized horses whose PaO2 increased following salbutamol inhalation. STUDY DESIGN: Retrospective, clinical, cohort study. ANIMALS: A group of 73 client-owned horses treated with salbutamol when PaO2 <100 mmHg (13.3 kPa) during anaesthesia. METHODS: Horses were divided into two groups: responders (R), where PaO2 after salbutamol ≥1.2 PaO2 before treatment (i.e. ≥20% increase), and non-responders (NR), where PaO2 after salbutamol <1.2 PaO2 before treatment. Demographic data and intraoperative variables before treatment were compared between R and NR. Cdyn, arterial to end-tidal carbon dioxide difference [P(a-E´)CO2], estimated ratio of dead space to tidal volume (est.VD/VT), estimated shunt fraction (F-shunt), heart rate, systolic, mean and diastolic arterial pressure and dobutamine requirements were compared before and after treatment within R and NR. For each variable, the difference (Δ) between values pre- and posttreatment was calculated and compared between groups R and NR. Numerical data were compared using univariate or bivariate analysis and categorical data were compared using chi-square test; p < 0.05. RESULTS: Of the 73 horses 50 were classified as R while 23 horses were classified as NR. There was no statistical difference between R and NR for demographic data or initial intraoperative variables except for body weight [R: 531 (170-715) kg, NR: 540 (420-914) kg]. While salbutamol did not alter Cdyn in either group, it significantly decreased P(a-E´)CO2, est.VD/VT and F-shunt in R only. ΔP(a-E´)CO2, Δest.VD/VT and ΔF-shunt were significantly greater in R (-17.8%, -19.0% and -24.1%, respectively) than in NR (11.5%, 6.6% and -0.3%, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: In hypoxaemic anaesthetized horses responding to inhaled salbutamol by a ≥1.2 increase in PaO2 no change in Cdyn was detected, but indicators of VË/ QË mismatch improved.
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Assessment of native cardiac output during extracorporeal circulation is challenging. We assessed a modified Fick principle under conditions such as dead space and shunt in 13 anesthetized swine undergoing centrally cannulated veno-arterial extracorporeal membrane oxygenation (V-A ECMO, 308 measurement periods) therapy. We assumed that the ratio of carbon dioxide elimination (VÌco2) or oxygen uptake (VÌo2) between the membrane and native lung corresponds to the ratio of respective blood flows. Unequal ventilation/perfusion (VÌ/QÌ) ratios were corrected towards unity. Pulmonary blood flow was calculated and compared to an ultrasonic flow probe on the pulmonary artery with a bias of 99 mL/min (limits of agreement -542 to 741 mL/min) with blood content VÌo2 and no-shunt, no-dead space conditions, which showed good trending ability (least significant change from 82 to 129 mL). Shunt conditions led to underestimation of native pulmonary blood flow (bias -395, limits of agreement -1,290 to 500 mL/min). Bias and trending further depended on the gas (O2, CO2) and measurement approach (blood content vs. gas phase). Measurements in the gas phase increased the bias (253 [LoA -1,357 to 1,863 mL/min] for expired VÌo2 bias 482 [LoA -760 to 1,724 mL/min] for expired VÌco2) and could be improved by correction of VÌ/QÌ inequalities. Our results show that common assumptions of the Fick principle in two competing circulations give results with adequate accuracy and may offer a clinically applicable tool. Precision depends on specific conditions. This highlights the complexity of gas exchange in membrane lungs and may further deepen the understanding of V-A ECMO.
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Oxigenação por Membrana Extracorpórea , Troca Gasosa Pulmonar , Animais , Suínos , Troca Gasosa Pulmonar/fisiologia , Oxigenação por Membrana Extracorpórea/métodos , Pulmão/irrigação sanguínea , Débito Cardíaco/fisiologia , Artéria Pulmonar , Dióxido de CarbonoRESUMO
The respiratory system plays an integral part in maintaining acid-base homeostasis. Normal ventilation participates in the maintenance of an open buffer system, allowing for excretion of CO2 produced from the interaction of nonvolatile acids and bicarbonate. Quantitatively of much greater importance is the excretion of CO2 derived from volatile acids produced from the complete oxidation of fat and carbohydrate. A primary increase in CO2 tension of body fluids is the cause of respiratory acidosis and develops most commonly from one or more of the following: (1) disorders affecting gas exchange across the pulmonary capillary, (2) disorders of the chest wall and the respiratory muscles, and/or (3) inhibition of the medullary respiratory center. Respiratory alkalosis or primary hypocapnia is most commonly caused by disorders that increase alveolar ventilation and is defined by an arterial partial pressure of CO2 <35 mm Hg with subsequent alkalization of body fluids. Both disorders can lead to life-threatening complications, making it of paramount importance for the clinician to have a thorough understanding of the cause and treatment of these acid-base disturbances.
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Acidose Respiratória , Alcalose Respiratória , Alcalose , Humanos , Alcalose Respiratória/diagnóstico , Alcalose Respiratória/etiologia , Dióxido de Carbono , Hipocapnia , Bicarbonatos , Alcalose/etiologia , Alcalose/complicações , Concentração de Íons de Hidrogênio , Equilíbrio Ácido-BaseRESUMO
INTRODUCTION: Electrical impedance tomography (EIT) can be used to assess ventilation/perfusion (V/Q) mismatch within the lungs. Several methods have been proposed, some of them neglecting the absolute value of alveolar ventilation (VA) and cardiac output (QC). Whether this omission results in acceptable bias is unknown. METHODS: Pixel-level V/Q maps of 25 ARDS patients were computed once considering (absolute V/Q map) and once neglecting (relative V/Q map) the value of QC and VA. Previously published indices of V/Q mismatch were computed using absolute V/Q maps and relative V/Q maps. Indices computed with relative V/Q maps were compared to their counterparts computed using absolute V/Q maps. RESULTS: Among 21 patients with ratio of alveolar ventilation to cardiac output (VA/QC) > 1, relative shunt fraction was significantly higher than absolute shunt fraction [37% (24-66) vs 19% (11-46), respectively, p < 0.001], while relative dead space fraction was significantly lower than absolute dead space fraction [40% (22-49) vs 58% (46-84), respectively, p < 0.001]. Relative wasted ventilation was significantly lower than the absolute wasted ventilation [16% (11-27) vs 29% (19-35), respectively, p < 0.001], while relative wasted perfusion was significantly higher than absolute wasted perfusion [18% (11-23) vs 11% (7-19), respectively, p < 0.001]. The opposite findings were retrieved in the four patients with VA/QC < 1. CONCLUSION: Neglecting cardiac output and alveolar ventilation when assessing V/Q mismatch indices using EIT in ARDS patients results in significant bias, whose direction depends on the VA/QC ratio value.
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Respiração , Síndrome do Desconforto Respiratório , Humanos , Impedância Elétrica , Perfusão , Tomografia Computadorizada por Raios X , Débito Cardíaco , PulmãoRESUMO
PURPOSE: This review recalls the principles developed over a century to describe trans-capillary fluid exchanges concerning in particular the lung during exercise, a specific condition where dyspnea is a leading symptom, the question being whether this symptom simply relates to fatigue or also implies some degree of lung edema. METHOD: Data from experimental models of lung edema are recalled aiming to: (1) describe how extravascular lung water is strictly controlled by "safety factors" in physiological conditions, (2) consider how waning of "safety factors" inevitably leads to development of lung edema, (3) correlate data from experimental models with data from exercising humans. RESULTS: Exercise is a strong edemagenic condition as the increase in cardiac output leads to lung capillary recruitment, increase in capillary surface for fluid exchange and potential increase in capillary pressure. The physiological low microvascular permeability may be impaired by conditions causing damage to the interstitial matrix macromolecular assembly leading to alveolar edema and haemorrhage. These conditions include hypoxia, cyclic alveolar unfolding/folding during hyperventilation putting a tensile stress on septa, intensity and duration of exercise as well as inter-individual proneness to develop lung edema. CONCLUSION: Data from exercising humans showed inter-individual differences in the dispersion of the lung ventilation/perfusion ratio and increase in oxygen alveolar-capillary gradient. More recent data in humans support the hypothesis that greater vasoconstriction, pulmonary hypertension and slower kinetics of alveolar-capillary O2 equilibration relate with greater proneness to develop lung edema due higher inborn microvascular permeability possibly reflecting the morpho-functional features of the air-blood barrier.
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Pulmão , Edema Pulmonar , Humanos , Edema Pulmonar/etiologia , Barreira Alveolocapilar , Água Extravascular Pulmonar/fisiologia , HipóxiaRESUMO
BACKGROUND: Oxidative stress associated with severe cardiopulmonary diseases leads to impairment in the nitric oxide/soluble guanylate cyclase signaling pathway, shifting native soluble guanylate cyclase toward heme-free apo-soluble guanylate cyclase. Here we describe a new inhaled soluble guanylate cyclase activator to target apo-soluble guanylate cyclase and outline its therapeutic potential. METHODS: We aimed to generate a novel soluble guanylate cyclase activator, specifically designed for local inhaled application in the lung. We report the discovery and in vitro and in vivo characterization of the soluble guanylate cyclase activator mosliciguat (BAY 1237592). RESULTS: Mosliciguat specifically activates apo-soluble guanylate cyclase leading to improved cardiopulmonary circulation. Lung-selective effects, e.g., reduced pulmonary artery pressure without reduced systemic artery pressure, were seen after inhaled but not after intravenous administration in a thromboxane-induced pulmonary hypertension minipig model. These effects were observed over a broad dose range with a long duration of action and were further enhanced under experimental oxidative stress conditions. In a unilateral broncho-occlusion minipig model, inhaled mosliciguat decreased pulmonary arterial pressure without ventilation/perfusion mismatch. With respect to airway resistance, mosliciguat showed additional beneficial bronchodilatory effects in an acetylcholine-induced rat model. CONCLUSION: Inhaled mosliciguat may overcome treatment limitations in patients with pulmonary hypertension by improving pulmonary circulation and airway resistance without systemic exposure or ventilation/perfusion mismatch. Mosliciguat has the potential to become a new therapeutic paradigm, exhibiting a unique mode of action and route of application, and is currently under clinical development in phase Ib for pulmonary hypertension.
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Hipertensão Pulmonar , Acetilcolina , Animais , Guanilato Ciclase/metabolismo , Guanilato Ciclase/uso terapêutico , Óxido Nítrico/metabolismo , Ratos , Guanilil Ciclase Solúvel/metabolismo , Guanilil Ciclase Solúvel/uso terapêutico , Suínos , Porco Miniatura/metabolismo , Tromboxanos/uso terapêutico , VasodilatadoresRESUMO
The oxygen deficit (OD) is the difference between the end-tidal alveolar Po2 and the calculated Po2 of arterial blood based on measured oxygen saturation that acts as a proxy for the alveolar-arterial Po2 difference. Previous work has shown that the alveolar gas meter (AGM100) can measure pulmonary gas exchange, via the OD, in patients with a history of lung disease and in normal subjects breathing 12.5% O2. The present study measured how the OD varied at different values of inspired O2. Healthy subjects were split by age (young 22-31; n = 23; older 42-90; n = 13). Across all inspired O2 levels (12.5, 15, 17.5, and 21%), the OD was higher in the older cohort 10.6 ± 1.0 mmHg compared with the young -0.4 ± 0.6 mmHg (P < 0.0001, using repeated measures ANOVA), the difference being significant at all O2 levels (all P < 0.0001). The OD difference between age groups and its variance was greater at higher O2 values (age × O2 interaction; P = 0.002). The decrease in OD with lower values of inspired O2 in both cohorts is consistent with the increased accuracy of the calculated arterial Po2 based on the O2-Hb dissociation curve and with the expected decrease in the alveolar-arterial Po2 difference due to a lower arterial saturation. The persisting higher OD seen in older subjects, irrespective of the inspired O2, shows that the measurement of OD remains sensitive to mild gas exchange impairment, even when breathing 21% O2.
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Oxigênio/administração & dosagem , Oxigênio/metabolismo , Troca Gasosa Pulmonar , Administração por Inalação , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: Behind armor blunt trauma (BABT) is a non-penetrating injury caused by the rapid deformation of body armor, by a projectile, which may in extreme circumstances cause death. Although there is not a high incidence of high energy BABT, the understanding of the mechanisms is still low, in relation to what is needed for safety threshold levels. BABT is also useful as a model for blunt thoracic trauma, with a compressive speed between traffic accidents and blast caused by explosives. High velocity projectile BABT causes severe hypoxia. The mechanisms are not fully known. We investigated the acute pulmonary consequences in the individual lungs, and the effects of alveolar recruitment. METHODS: 12 swine (mean weight 62.5 kg) were randomized to groups BABT by 7.62 × 51 mm NATO-type bullets (mean velocity 803 m/s) to a military grade ceramic plate armor (n = 7) or control (n = 5). Modified double lumen tracheal tubes provided respiratory dynamics in the lungs separately/intermittently for two hours, with alveolar recruitment after one hour. RESULTS: Venous admixture increased 5 min after BABT (p < .05) and correlated with increased cardiac output. Static compliance decreased 5 minutes after BABT (p < .05) and further by recruitment (p < .005). Physiological dead space decreased 5 minutes after BABT (p < .01) and further by recruitment (p < .01), while not in the contralateral lung. V'A/Q' decreased 5 minutes after BABT (p < .05), also shown in phase III volumetric capnography (p < .05). Most effects regressed after one hour. CONCLUSIONS: High velocity projectile BABT caused hypoxia by a severe and transient decrease in V'A/Q' to <1 and increased venous admixture in the exposed lung. Alveolar recruitment was hemodynamically and respiratory tolerable and increased V'A/Q'. Body armor development should aim at ameliorating severe pulmonary consequences from high projectile velocities which also needs to include further understanding of how primary and secondary effects are distributed between the lungs.
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Pneumopatias/patologia , Pulmão/patologia , Ventilação Pulmonar/fisiologia , Ferimentos não Penetrantes/patologia , Animais , Modelos Animais de Doenças , Feminino , Hipóxia/patologia , Masculino , Perfusão/métodos , Pressão , Suínos , Traumatismos Torácicos/patologiaRESUMO
BACKGROUND: Several studies have found only a weak to moderate correlation between oxygenation and lung aeration in response to changes in PEEP. This study aimed to investigate the association between changes in shunt, low and high ventilation/perfusion (V/Q) mismatch, and computed tomography-measured lung aeration following an increase in PEEP in patients with ARDS. METHODS: In this preliminary study, 12 ARDS patients were subjected to recruitment maneuvers followed by setting PEEP at 5 and then either 15 or 20 cmH2O. Lung aeration was measured by computed tomography. Values of pulmonary shunt and low and high V/Q mismatch were calculated by a model-based method from measurements of oxygenation, ventilation, and metabolism taken at different inspired oxygen levels and an arterial blood gas sample. RESULTS: Increasing PEEP resulted in reduced values of pulmonary shunt and the percentage of non-aerated tissue, and an increased percentage of normally aerated tissue (p < 0.05). Changes in shunt and normally aerated tissue were significantly correlated (r = - 0.665, p = 0.018). Three distinct responses to increase in PEEP were observed in values of shunt and V/Q mismatch: a beneficial response in seven patients, where shunt decreased without increasing high V/Q; a detrimental response in four patients where both shunt and high V/Q increased; and a detrimental response in a patient with reduced shunt but increased high V/Q mismatch. Non-aerated tissue decreased with increased PEEP in all patients, and hyperinflated tissue increased only in patients with a detrimental response in shunt and V/Q mismatch. CONCLUSIONS: The results show that improved lung aeration following an increase in PEEP is not always consistent with reduced shunt and V/Q mismatch. Poorly matched redistribution of ventilation and perfusion, between dependent and non-dependent regions of the lung, may explain why patients showed detrimental changes in shunt and V/Q mismatch on increase in PEEP, despite improved aeration. TRIAL REGISTRATION: ClinicalTrails.gov, NCT04067154. Retrospectively registered on August 26, 2019.
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Respiração com Pressão Positiva/métodos , Síndrome do Desconforto Respiratório/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Relação Ventilação-Perfusão/fisiologia , Adulto , Idoso , Gasometria/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Respiração com Pressão Positiva/instrumentação , Estudos Prospectivos , Síndrome do Desconforto Respiratório/complicaçõesRESUMO
BACKGROUND AND OBJECTIVE: Respiratory muscle weakness causes fatigue in these muscles during exercise and thereby increases dead-space ventilation ratio with decreased tidal volume. However, it remains unclear whether respiratory muscle weakness aggravates ventilation-perfusion mismatch through the increased dead-space ventilation ratio. In ventilation-perfusion mismatch during exercise, minute ventilation versus carbon dioxide production (VE/VCO2 ) slope > 34 is an indicator of poor prognosis in patients with chronic heart failure (CHF). We examined the relationship of respiratory muscle weakness with dead-space ventilation ratio and ventilation-perfusion mismatch during exercise and clarified whether respiratory muscle weakness was a clinical predictor of VE/VCO2 slope > 34 in patients with CHF. METHODS: Maximal inspiratory pressure (PImax ) was measured as respiratory muscle strength 2 months after hospital discharge in 256 compensated patients with CHF. During cardiopulmonary exercise test, we assessed minute dead-space ventilation versus VE (VD/VE ratio) as dead-space ventilation ratio and VE/VCO2 slope as ventilation-perfusion mismatch. Patients were divided into low, moderate and high PImax groups based on the PImax tertile. We investigated determinants of VE/VCO2 slope > 34 among these groups. RESULTS: The low PImax group showed significantly higher VD/VE ratios at 50% of peak workload and at peak workload and higher VE/VCO2 slope than the other two groups (P < 0.001, respectively). PImax was a significant independent determinant of VE/VCO2 slope > 34 (odds ratio (OR): 0.67, 95% CI: 0.54-0.82) with area under the receiver operating characteristic curve of 0.812 (95% CI: 0.750-0.874). CONCLUSION: Respiratory muscle weakness was associated with an increased dead-space ventilation ratio aggravating ventilation-perfusion mismatch during exercise in patients with CHF.
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Tolerância ao Exercício , Insuficiência Cardíaca , Debilidade Muscular , Músculos Respiratórios/fisiopatologia , Relação Ventilação-Perfusão , Correlação de Dados , Exercício Físico/fisiologia , Teste de Esforço/métodos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/complicações , Debilidade Muscular/fisiopatologia , Consumo de Oxigênio , Espaço Morto RespiratórioRESUMO
OBJECTIVE: To determine the blood sevoflurane and desflurane concentrations during one-lung ventilation (OLV). DESIGN: Randomized, single-blind study. SETTING: Single university hospital. PARTICIPANTS: The study comprised 24 patients, 35 to 70 years old who were scheduled for either a major abdominal surgery or thoracotomy. INTERVENTIONS: The patients were divided into the following 4 groups: sevoflurane two-lung ventilation (TLV), sevoflurane OLV, desflurane TLV, and desflurane OLV. Vaporizers were set at 1.5% sevoflurane or 6% desflurane. MEASUREMENTS AND MAIN RESULTS: In the TLV groups, blood samples were taken in 10-minute intervals starting 40 minutes after the start of TLV (T1-T9) for blood gas analysis and gas chromatography. In the OLV groups, the first sample was collected at 40 minutes of TLV (T1), and other samples were collected in 10-minute intervals from the start of OLV (T2-T9). Saturation of peripheral oxygen (SpO2), hemodynamic variables, and inspired and end-tidal volatiles were recorded. The fraction uptake of the volatile agents (F) was calculated for each patient at the same time points. The mean arterial sevoflurane concentration in the sevoflurane OLV group at T1 decreased from 40.7 ± 4.4 to 30.2 ± 2.5 µg/mL at T3 (pâ¯=â¯0.014, 26% decrease). In the OLV desflurane group, the mean arterial desflurane concentration at T1 declined from 224.6 ± 44.8 to 159.8 ± 32 µg/mL at T3 (p=0.018, 29% decrease). However, the reduction of sevoflurane concentration compared with that of desflurane at T3 was not statistically significant (pâ¯=â¯0.31). In addition, the fraction uptake of the volatile agents values significantly increased at the start of OLV (p = 0.001). CONCLUSION: An OLV procedure causes a decrease in the both arterial and venous blood concentrations of sevoflurane and desflurane. This reduction is believed to be due to ventilation-perfusion mismatch.
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Anestesia Geral/métodos , Desflurano/farmacocinética , Hipóxia/sangue , Monitorização Intraoperatória/métodos , Ventilação Monopulmonar/métodos , Sevoflurano/farmacocinética , Adulto , Idoso , Anestésicos Inalatórios/farmacocinética , Biomarcadores/sangue , Gasometria , Cromatografia Gasosa , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Procedimentos Cirúrgicos TorácicosRESUMO
Current therapeutic methods for chronic thromboembolic pulmonary hypertension (CTEPH) can improve hemodynamic status and are expected to improve prognoses. However, some patients experience dyspnea during effort and continue supplemental oxygenation despite their hemodynamic status being fully improved. Considering the pathogenesis of CTEPH, the dead space and intrapulmonary shunt are assumed to be responsible for hypoxia in CTEPH, but their contributions are unclear. It is also unclear whether they are improved after treatment. The aim of this study was to investigate the implications of the dead space ratio (DSR) and the intrapulmonary shunt ratio (ISR) for hypoxia in CTEPH and treatment for CTEPH.We retrospectively measured the DSR and ISR of 23 consecutive patients with CTEPH. For 11 of these 23 (10 were treated by balloon pulmonary angioplasty, one with riociguat), we also measured these parameters before and after CTEPH treatments. Overall, the DSR and ISR were abnormally elevated (DSR: 0.63 ± 0.06; ISR: 0.20 ± 0.05). After treatment, mean pulmonary artery pressure was improved (from 40.3 ± 8.1 to 25.5 ± 2.7 mmHg). Although atrial oxygen saturation (SaO2), DSR and ISR were improved (SaO2: from 90.2 ± 3.2 to 93.7 ± 1.8%; DSR: from 0.64 ± 0.06 to 0.58 ± 0.05; ISR: from 0.20 ± 0.04 to 0.18 ± 0.02), these improvements were slight compared with that of mean pulmonary artery pressure.The DSR and ISR were abnormally elevated in patients with CTEPH and their improvement by treatment was limited. Only DSR can be a useful marker for normalization of hypoxia in CTEPH.
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Angioplastia com Balão/métodos , Hipertensão Pulmonar/terapia , Embolia Pulmonar/terapia , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Espaço Morto Respiratório/efeitos dos fármacos , Adulto , Idoso , Doença Crônica , Feminino , Hemodinâmica/fisiologia , Hospitais Universitários , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/mortalidade , Japão , Masculino , Pessoa de Meia-Idade , Oxigenoterapia/métodos , Prognóstico , Circulação Pulmonar/fisiologia , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Espaço Morto Respiratório/fisiologia , Testes de Função Respiratória , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Stenting at the flow-limiting segment can improve the ventilation-perfusion ratio in patients with central airway stenosis. However, there is no quantitative examination for assessing the perfusion status during interventional bronchoscopy. Intrabronchial capnography can estimate regional gas exchange by measuring carbon dioxide concentration. We herein report a case of bilateral bronchial stenosis where stenting was able to improve ventilation-perfusion ratio using intrabronchial capnography. A 44-year-old man was admitted to our institution with orthopnea. Chest computed tomography showed an extrinsic compression at the bilateral main bronchus and right pulmonary artery due to a mediastinal mass. After introduction of general anesthesia, arterial oxygen tension suddenly decreased in the supine position. After initial stenting, an increase was seen in ventilation at the right lung; however, a ventilation-perfusion mismatch occurred due to an increase in dead-space ventilation at the right pulmonary artery stenosis. Intrabronchial capnography was an effective modality to confirm the regional perfusion status during interventional bronchoscopy in real time.
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Broncopatias/complicações , Estenose de Artéria Pulmonar/diagnóstico , Adulto , Broncoscopia , Capnografia , Humanos , Masculino , Circulação Pulmonar , Estenose de Artéria Pulmonar/complicações , Estenose de Artéria Pulmonar/fisiopatologiaRESUMO
Undergraduate biomedical students often have difficulties in understanding basic concepts of respiratory physiology, particularly respiratory mechanics. In this study, we report the use of electrical impedance tomography (EIT) to improve and consolidate the knowledge about physiological aspects of normal regional distribution of ventilation in humans. Initially, we assessed the previous knowledge of a group of medical students ( n = 39) about regional differences in lung ventilation. Thereafter, we recorded the regional distribution of ventilation through surface electrodes on a healthy volunteer adopting four different decubitus positions: supine, prone, and right and left lateral. The recordings clearly showed greater pulmonary ventilation in the dependent lung, mainly in the lateral decubitus. Considering the differences in pulmonary ventilation between right and left lateral decubitus, only 33% of students were able to notice it correctly beforehand. This percentage increased to 84 and 100%, respectively ( P < 0.01), after the results of the ventilation measurements obtained with EIT were examined and discussed. A self-assessment questionnaire showed that students considered the practical activity as an important tool to assist in the understanding of the basic concepts of respiratory mechanics. Experimental demonstration of the physiological variations of regional lung ventilation in volunteers by using EIT is feasible, effective, and stimulating for undergraduate medical students. Therefore, this practical activity may help faculty and students to overcome the challenges in the field of respiratory physiology learning.
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Educação Médica/métodos , Impedância Elétrica , Fisiologia/educação , Ventilação Pulmonar/fisiologia , Estudantes de Medicina , Tomografia/métodos , Compreensão/fisiologia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Bronchial epithelial cells and pulmonary endothelial cells are thought to be the primary modulators of conducting airways and vessels, respectively. However, histological examination of both mouse and human lung tissue reveals that alveolar epithelial cells (AECs) line the adventitia of large airways and vessels and thus are also in a position to directly regulate these structures. The primary purpose of this perspective is to highlight the fact that AECs coat the adventitial surface of every vessel and airway in the lung parenchyma. This localization is ideal for transmitting signals that can contribute to physiologic and pathologic responses in vessels and airways. A few examples of mediators produced by AECs that may contribute to vascular and airway responses are provided to illustrate some of the potential effects that AECs may modulate.
Assuntos
Células Epiteliais Alveolares/metabolismo , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Células Epiteliais Alveolares/imunologia , Animais , Humanos , Imunidade Inata , Pulmão/fisiologia , Modelos BiológicosRESUMO
BACKGROUND: In acute respiratory respiratory distress syndrome (ARDS) a sustained mismatch of alveolar ventilation and perfusion (VA/Q) impairs the pulmonary gas exchange. Measurement of endexpiratory lung volume (EELV) by multiple breath-nitrogen washout/washin is a non-invasive, bedside technology to assess pulmonary function in mechanically ventilated patients. The present study examines the association between EELV changes and VA/Q distribution and the possibility to predict VA/Q normalization by means of EELV in a porcine model. METHODS: After approval of the state and institutional animal care committee 12 anesthetized pigs were randomized to ARDS either by bronchoalveolar lavage (n = 6) or oleic acid injection (n = 6). EELV, VA/Q ratios by multiple inert gas elimination and ventilation distribution by electrical impedance tomography were assessed at healthy state and at five different positive endexpiratory pressure (PEEP) steps in ARDS (0, 20, 15, 10, 5 cmH2O; each maintained for 30 min). RESULTS: VA/Q, EELV and tidal volume distribution all displayed the PEEP-induced recruitment in ARDS. We found a close correlation between VA/Q < 0.1 (representing shunt and low VA/Q units) and changes in EELV (spearman correlation coefficient -0.79). Logistic regression reveals the potential to predict VA/Q normalization (VA/Q < 0.1 less than 5%) from changes in EELV with an area under the curve of 0.89 with a 95%-CI of 0.81-0.96 in the receiver operating characteristic. Different lung injury models and recruitment characteristics did not influence these findings. CONCLUSION: In a porcine ARDS model EELV measurement depicts PEEP-induced lung recruitment and is strongly associated with normalization of the VA/Q distribution in a model-independent fashion. Determination of EELV could be an intriguing addition in the context of lung protection strategies.
Assuntos
Lesão Pulmonar/fisiopatologia , Ventilação Pulmonar/fisiologia , Síndrome do Desconforto Respiratório/fisiopatologia , Animais , Volume Expiratório Forçado/fisiologia , Medidas de Volume Pulmonar/métodos , Masculino , Pico do Fluxo Expiratório/fisiologia , SuínosRESUMO
Background: The effects of obesity on pulmonary gas and blood distribution in patients with acute respiratory failure remain unknown. Dual-energy computed tomography (DECT) is a X-ray-based method used to study regional distribution of gas and blood within the lung. We hypothesized that 1) regional gas/blood mismatch can be quantified by DECT; 2) obesity influences the global and regional distribution of pulmonary gas and blood; 3) regardless of ventilation modality (invasive vs. non-invasive ventilation), patients' body mass index (BMI) has an impact on pulmonary gas/blood mismatch. Methods: This single-centre prospective observational study enrolled 118 hypoxic COVID-19 patients (92 male) in need of respiratory support and intensive care who underwent DECT. The cohort was divided into three groups according to BMI: 1. BMI<25 kg/m2 (non-obese), 2. BMI = 25-40 kg/m2 (overweight to obese), and 3. BMI>40 kg/m2 (morbidly obese). Gravitational analysis of Hounsfield unit distribution of gas and blood was derived from DECT and used to calculate regional gas/blood mismatch. A sensitivity analysis was performed to investigate the influence of the chosen ventilatory modality and BMI on gas/blood mismatch and adjust for other possible confounders (i.e., age and sex). Results: 1) Regional pulmonary distribution of gas and blood and their mismatch were quantified using DECT imaging. 2) The BMI>40 kg/m2 group had less hyperinflation in the non-dependent regions and more lung collapse in the dependent regions compared to the other BMI groups. In morbidly obese patients, gas and blood were more evenly distributed; therefore, the mismatch was lower than in other patients (30% vs. 36%, p < 0.05). 3) An increase in BMI of 5 kg/m2 was associated with a decrease in mismatch of 3.3% (CI: 3.67% to -2.93%, p < 0.05). Neither the ventilatory modality nor age and sex affected the gas/blood mismatch (p > 0.05). Conclusion: 1) In a hypoxic COVID-19 population needing intensive care, pulmonary gas/blood mismatch can be quantified at a global and regional level using DECT. 2) Obesity influences the global and regional distribution of gas and blood within the lung, and BMI>40 kg/m2 improves pulmonary gas/blood mismatch. 3) This is true regardless of the ventilatory mode and other possible confounders, i.e., age and sex. Trial Registration: Clinicaltrials.gov, identifier NCT04316884, NCT04474249.