Search Results (18)

Interest in the subject of umbilical cord clamping is long-standing. New evidence reveals that placental transfusion, facilitated by delayed cord clamping (DCC), reduces death and need for blood transfusions for preterm infants without evidence of harm. Even a brief delay in clamping the cord shows improved survival and well-being, but waiting at least two minutes is even better. We propose that three major benefits from DCC contribute to reduced mortality of preterm infants: (1) benefits from the components of blood; (2) assistance from the continued circulation of blood; and (3) the essential mechanical interactions that result from the enhanced volume of blood. The enhanced blood volume generates mechanical forces within the microcirculation that support the newborn’s metabolic and cardiovascular stability and secure short- and long-term organ health. Several unique processes prime preterm and term newborns to receive the full placental transfusion, not to be misinterpreted as extra blood or over-transfusion. Disrupting cord circulation before the newborn’s lung capillary bed has been fully recruited and the lungs can replace the placenta as a respiratory, gas-exchanging organ may be harmful. Early cord clamping also denies the newborn a full quota of iron-rich red blood cells as well as valuable stem cells for regeneration, repair, and seeding of a strong immune system. We propose that delayed cord clamping and intact-cord stabilization have the potential to save lives by protecting many neonates from hypovolemia, inflammation, and ischemia. Full article

Impaired lung gas exchange is commonly seen in patients with pulmonary involvement related to SARS-CoV-2 acute infection or post-acute COVID-19 syndrome (PACS). The primary aim of our study was to assess lung gas transfer, measuring the pulmonary diffusion capacity for nitric oxide (D_LNO) and carbon monoxide (D_LCO) in all COVID-19 patients. Our secondary aim was to decipher the respective roles of perturbed lung membrane conductance (D_M) and reduced pulmonary capillary volume (V_C) in patients with impaired lung gas exchange. From May to October 2020, we measured D_LNO-D_LCO in 118 patients during their post-COVID-19 period (4.6 months after infection) to decipher alveolo-capillary gas transfer disturbances. D_LNO-D_LCO measurement was also performed in 28 healthy non-smokers as controls. Patients were classified into three groups according to the severity (mild, moderate, and severe) of acute COVID-19 infection. Patients with mild COVID-19 had normal lung volumes and airways expiratory flows but impaired pulmonary gas exchange, as shown by the significant decreases in D_LNO, D_LCO, D_M, and V_C as compared with controls. V_C was significantly impaired and the D_LNO/D_LCO ratio was increased in patients with moderate (n = 4, 11%) and severe COVID-19 (n = 23, 49%). Abnormal membrane conductance was also seen in all three groups of post-COVID-19 patients. These findings suggest a persistent alveolo-capillary gas transfer defect, implying not only reduced membrane conductance but also abnormal pulmonary vascular capacitance in all PACS patients, even those with a milder form of COVID-19 infection. Full article

Backgrounds and Aims: Patients with cirrhosis are susceptible to sepsis and septic shock. Cirrhotic patients also have increased capillary permeability and are prone to developing volume overload. Patients with septic shock may have an enhanced pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), both of which are associated with an unfavorable prognosis. It is plausible that pre-existing hyperpermeability may deteriorate when cirrhotic patients develop septic shock. However, it remains unknown whether PVPI and EVLWI can predict the prognosis of cirrhotic patients with septic shock. Pulse Indicator Continuous Cardiac Output (PiCCO) is an established tool to measure PVPI and EVLWI. Therefore, we conducted this retrospective study to investigate the prognostic significance of PVPI and EVLWI in cirrhotic patients with septic shock using PiCCO monitoring. Methods: We included 83 patients with liver cirrhosis and septic shock. EVLW indexed to actual body weight (aEVLWI), EVLW indexed to predicted body weight (pEVLWI), PVPI, disease severity scores, and other biomarkers were analyzed. We collected the PiCCO data on the first 2 days. Results: The overall 28-day mortality was 43.4%. The values of PVPI, aEVLWI, and pEVLWI on day 2 (PVPID2, aEVLWID2, EVLWID2) were significantly higher in non-survivors. The discriminating power of PVPID2 and EVLWID2 to predict 28-day mortality was tested using the area under a ROC curve. The areas under ROC curves (mean ± SEM) were 0.713 ± 0.061 and 0.650 ± 0.063 for PVPID2 and pEVLWID2. In the multivariate analysis, PVPID2, bilirubin, and lactate were independent factors which predicted 28-day mortality. Conclusions: Higher levels of PVPID2 and pEVLWID2 are associated with higher 28-day mortality rates in cirrhotic patients with septic shock. PVPI and pEVLWI may be useful to guide fluid management in this clinical setting. Full article

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), are characterized by uncontrolled inflammatory responses, neutrophil activation and infiltration, damage to the alveolar capillary membrane, and diffuse alveolar injury. Neutrophil extracellular traps (NETs), formed by activated neutrophils, contribute significantly to various inflammatory disorders and can lead to tissue damage and organ dysfunction. Corilagin, a compound found in Phyllanthus urinaria, possesses antioxidative and anti-inflammatory properties. In this study, we investigated the protective effects and underlying mechanisms of corilagin in hydrochloric acid (HCl)/lipopolysaccharide (LPS)-induced lung injury. Mice received intraperitoneal administration of corilagin (2.5, 5, or 10 mg/kg) or an equal volume of saline 30 min after intratracheal HCl/LPS administration. After 20 h, lung tissues were collected for analysis. Corilagin treatment significantly mitigated lung injury, as evidenced by reduced inflammatory cell infiltration, decreased production of proinflammatory cytokines, and alleviated oxidative stress. Furthermore, corilagin treatment suppressed neutrophil elastase expression, reduced NET formation, and inhibited the expression of ERK, p38, AKT, STAT3, and NOX2. Our findings suggest that corilagin inhibits NET formation and protects against HCl/LPS-induced ALI in mice by modulating the STAT3 and NOX2 signaling pathways. Full article

Introduction: Acute hypercapnic respiratory failure has a poor prognosis in patients with interstitial lung disease (ILD). Recent data demonstrated a positive effect of nasal high-flow (NHF) in patients with acute hypoxemic respiratory failure. Preliminary data also show benefits in several hypercapnic chronic lung diseases. Objectives: The aim of this study was to characterize flow-dependent changes in mean airway pressure, breathing volumes, and breathing frequency and decreases in PCO₂. Methods: Mean airway pressure was measured in the nasopharyngeal space. To evaluate breathing volumes, a polysomnographic device was used (16 patients). All subjects received 20, 30, 40, and 50 L/min and—to illustrate the effects—nCPAP and nBiPAP. Capillary blood gas analyses were performed in 25 hypercapnic ILD subjects before and 5 h after the use of NHF. Additionally, comfort and dyspnea during the use of NHF were surveyed. Results: NHF resulted in a small flow-dependent increase in mean airway pressure. Tidal volume was unchanged and breathing rate decreased. The calculated minute volume decreased by 20 and 30 L/min NHF breathing. In spite of this fact, hypercapnia decreased at a flow rate of 24 L/min. Additionally, an improvement in dyspnea was observed. Conclusions: NHF leads to a reduction in paCO₂. This is most likely achieved by a washout of the respiratory tract and a reduction in functional dead space. NHF enhances the effectiveness of breathing in ILD patients by the reduction in respiratory rate. In summary, NHF works as an effective ventilatory support device in hypercapnic ILD patients. Full article

Tuberculosis-related lung damage is very different. Lung ventilation disorders have been studied in patients with pulmonary tuberculosis (TB) during the active process and after treatment, but the main causes of gas exchange changes have not been sufficiently studied. Investigation of diffusing lung capacity in combination with bodyplethysmography is useful for the interpretation of pulmonary gas exchange disorders. The aim was to determine the relationship of gas exchange with the value of alveolar volume (VA) and pulmonary poorly communicating fraction (PCF) in patients with pulmonary TB. A total of 292 patients (117/175 M/W) with verified pulmonary TB with smoking age less than 10 packs-years underwent spirometry, bodyplethysmography, and D_LCO by the single-breath method. PCF was estimated calculating the difference between total lung capacity (TLC) and VA (% TLC). Patients with low D_LCO had statistically significantly lower spirometric values (FVC, FEV₁, FEV₁/FVC, MMEF), lower TLC, higher airway resistance, RV/TLC, air-trapping volume, and PCF. The patients with low level of D_LCO were divided into four groups depending on level VA and PCF. In most patients with infiltrative tuberculosis (50%), the leading syndrome of the D_LCO decrease was alveolar-capillary damage. In patients with tuberculomas, the syndromes of alveolar capillary damage and pulmonary ventilation inhomogeneity were with the same frequency (43%). In patients with disseminated tuberculosis, the most frequent syndrome of the D_LCO decrease was pulmonary ventilation inhomogeneity (33%), then alveolar-capillary damage (29%) and mixed (24%). In patients with cavernous tuberculosis, the leading syndrome of the D_LCO decrease was mixed (39%), then alveolar capillary damage (25%) and pulmonary ventilation inhomogeneity (23%). The syndrome of gas exchange surface reduction in patients with disseminated and cavernous tuberculosis was less common (14%). In conclusion, an additional evaluation of the combination of PCF and VA increases the amount of clinical information obtained using the diffusion lung capacity measurements, since it allows identifying various syndromes of gas exchange impairment. The leading causes of diffusing capacity impairment vary by different types of pulmonary TB. Full article

The lung promptly responds to edemagenic conditions through functional adaptations that contrast the increase in microvascular filtration. This review presents evidence for early signaling transduction by endothelial lung cells in two experimental animal models of edema, hypoxia exposure, and fluid overload (hydraulic edema). The potential role of specialized sites of the plasma membranes considered mobile signaling platforms, referred to as membrane rafts, that include caveolae and lipid rafts, is presented. The hypothesis is put forward that early changes in the lipid composition of the bilayer of the plasma membrane might trigger the signal transduction process when facing changes in the pericellular microenvironment caused by edema. Evidence is provided that for an increase in the extravascular lung water volume not exceeding 10%, changes in the composition of the plasma membrane of endothelial cells are evoked in response to mechanical stimuli from the interstitial compartment as well as chemical stimuli relating with changes in the concentration of the disassembled portions of structural macromolecules. In hypoxia, thinning of endothelial cells, a decrease in caveolae and AQP-1, and an increase in lipid rafts are observed. The interpretation of this response is that it favors oxygen diffusion and hinder trans-cellular water fluxes. In hydraulic edema, which generates greater capillary water leakages, an increase in cell volume and opposite changes in membrane rafts were observed; further, the remarkable increase in caveolae suggests a potential abluminal–luminal vesicular-dependent fluid reabsorption. Full article

This study was performed to visualize the hemodynamic effects of pulmonary microcirculation and ventilation/perfusion (V/Q) matching after mechanical ventilation under different cardiac outputs and positive end-expiratory pressures (PEEPs). Ten experimental pigs were randomly divided into high and low tidal volume groups, and ventilation/perfusion were measured by electrical impedance tomography (EIT) at different PEEPs. Then, all the pigs were redivided into high cardiac output (CO) and low CO groups and measured by EIT at different PEEP levels with a low tidal volume. Additionally, sidestream dark field (SDF) was used to measure pulmonary microcirculation. Hemodynamic parameters and respiratory mechanics parameters were recorded. As PEEP increased at high tidal volume, blood flow was impaired at a higher PEEP (20 cmH₂O) compared with low tidal volume (shunt: 30.01 ± 0.69% vs. 17.95 ± 0.72%; V/Q ratio: 65.12 ± 1.97% vs. 76.57 ± 1.25%, p < 0.01). Low tidal volume combined with an appropriate PEEP is the best option from the match between ventilation and pulmonary blood flow. Increasing PEEP can solve the problem of excessive shunt at high CO, and the V/Q ratio tends to match. At low CO, the increased dead space can reach as high as 64.64 ± 7.13% when PEEP = 20 cmH₂O. With increasing PEEP, the microcirculation index deteriorates, including total vessel density (TVD), proportion of perfused vessel (PPV), perfused vessel density (PVD), and microcirculatory flow index (MFI). The periodic collapse of pulmonary capillaries or interruption of blood flow obviously occurred with high PEEP. The hemodynamic parameters indicated that the transpulmonary capillary wall pressure (Pcap) of the low CO group was negative at PEEP = 5 cmH₂O, which determines the opening and closing of the pulmonary microcirculation and controls lung perfusion and the production of extravascular lung water. Therefore, it is essential to couple macrocirculation and pulmonary microcirculation during mechanical ventilation by improving shunting and optimizing Pcap. Full article

After stroke and other brain injuries, there is a high incidence of respiratory complications such as pneumonia or acute lung injury. The molecular mechanisms that drive the brain-lung interaction post-stroke have not yet been elucidated. We performed transient middle cerebral artery occlusion (MCAO) and sham surgery on C57BL/6J mice and collected bronchoalveolar lavage fluid (BALF), serum, brain, and lung homogenate samples 24 h after surgery. A 92 proteins-panel developed by Olink Proteomics^® was used to analyze the content in BALF and lung homogenates. MCAO animals had higher protein concentration levels in BALF than sham-controls, but these levels did not correlate with the infarct volume. No alteration in alveolar-capillary barrier permeability was observed. A total of 12 and 14 proteins were differentially expressed between the groups (FDR < 0.1) in BALF and lung tissue homogenates, respectively. Of those, HGF, TGF-α, and CCL2 were identified as the most relevant to this study. Their protein expression patterns were verified by ELISA. This study confirmed that post-stroke lung damage was not associated with increased lung permeability or cerebral ischemia severity. Furthermore, the dysregulation of HGF, TGF-α, and CCL2 in BALF and lung tissue after ischemia could play an important role in the molecular mechanisms underlying stroke-induced lung damage. Full article

Microfluidic artificial lungs (μALs) are being investigated for their ability to closely mimic the size scale and cellular environment of natural lungs. Researchers have developed μALs with small artificial capillary diameters (10–50 µm; to increase gas exchange efficiency) and with large capillary diameters (~100 µm; to simplify design and construction). However, no study has directly investigated the impact of capillary height on μAL properties. Here, we use Murray’s law and the Hagen-Poiseuille equation to design single-layer, small-scale μALs with capillary heights between 10 and 100 µm. Each µAL contained two blood channel types: capillaries for gas exchange; and distribution channels for delivering blood to/from capillaries. Three designs with capillary heights of 30, 60, and 100 µm were chosen for further modeling, implementation and testing with blood. Flow simulations were used to validate and ensure equal pressures. Designs were fabricated using soft lithography. Gas exchange and pressure drop were tested using whole bovine blood. All three designs exhibited similar pressure drops and gas exchange; however, the μAL with 60 µm tall capillaries had a significantly higher wall shear rate (although physiologic), smaller priming volume and smaller total blood contacting surface area than the 30 and 100 µm designs. Future μAL designs may need to consider the impact of capillary height when optimizing performance. Full article

We use a case of intact cord resuscitation to argue for the beneficial effects of an enhanced blood volume from placental transfusion for newborns needing resuscitation. We propose that intact cord resuscitation supports the process of physiologic neonatal transition, especially for many of those newborns appearing moribund. Transfer of the residual blood in the placenta provides the neonate with valuable access to otherwise lost blood volume while changing from placental respiration to breathing air. Our hypothesis is that the enhanced blood flow from placental transfusion initiates mechanical and chemical forces that directly, and indirectly through the vagus nerve, cause vasodilatation in the lung. Pulmonary vascular resistance is thereby reduced and facilitates the important increased entry of blood into the alveolar capillaries before breathing commences. In the presented case, enhanced perfusion to the brain by way of an intact cord likely led to regained consciousness, initiation of breathing, and return of tone and reflexes minutes after birth. Paramount to our hypothesis is the importance of keeping the umbilical cord circulation intact during the first several minutes of life to accommodate physiologic neonatal transition for all newborns and especially for those most compromised infants. Full article

This study compared the effects of varying aerobic training programs on pulmonary diffusing capacity (TL_CO), pulmonary diffusing capacity for nitric oxide (TL_NO), lung capillary blood volume (Vc) and alveolar–capillary membrane diffusing capacity (DM) of gases at rest and just after maximal exercise in young athletes. Sixteen healthy young runners (16–18 years) were randomly assigned to an intense endurance training program (IET, n = 8) or to a moderate endurance training program (MET, n = 8). The training volume was similar in IET and MET but with different work intensities, and each lasted for 8 weeks. Participants performed a maximal graded cycle bicycle ergometer test to measure maximal oxygen consumption (VO₂max) and maximal aerobic power (MAP) before and after the training programs. Moreover, TL_CO, TL_NO and Vc were measured during a single breath maneuver. After eight weeks of training, all pulmonary parameters with the exception of alveolar volume (VA) and inspiratory volume (VI) (0.104 < p < 0889; 0.001 < ES < 0.091), measured at rest and at the end of maximal exercise, showed significant group × time interactions (p < 0.05, 0.2 < ES < 4.0). Post hoc analyses revealed significant pre-to-post decreases for maximal heart rates (p < 0.0001, ES = 3.1) and improvements for VO₂max (p = 0.006, ES = 2.22) in the IET group. Moreover, post hoc analyses revealed significant pre-to-post improvements in the IET for DM, TL_NO, TL_CO and Vc (0.001 < p < 0.0022; 2.68 < ES < 6.45). In addition, there were increases in Vc at rest, VO₂max, TL_NO and DM in the IET but not in the MET participants after eight weeks of training with varying exercise intensities. Our findings suggest that the intensity of training may represent the most important factor in increasing pulmonary vascular function in young athletes. Full article

Swimming exercise at sea level causes a transient decrease in lung diffusing capacity for carbon monoxide (DL_CO). The exposure to hypobaric hypoxia can affect lung gas exchange, and hypoxic pulmonary vasoconstriction may elicit pulmonary oedema. The purpose of this study is to evaluate whether there are changes in DL_CO during a 14-day altitude training camp (1850 m) in elite swimmers and the acute effects of a combined training session of swimming in moderate hypoxia and 44-min cycling in acute normobaric severe hypoxia (3000 m). Participants were eight international level swimmers (5 females and 3 males; 17–24 years old; 173.5 ± 5.5 cm; 64.4 ± 5.3 kg) with a training volume of 80 km per week. The single-breath method was used to measure the changes in DL_CO and functional gas exchange parameters. No changes in DL_CO after a 14-day altitude training camp at 1850 m were detected but a decrease in alveolar volume (VA; 7.13 ± 1.61 vs. 6.50 ± 1.59 L; p = 0.005; d = 0.396) and an increase in the transfer coefficient of the lung for carbon monoxide (K_CO; 6.23 ± 1.03 vs. 6.83 ± 1.31 mL·min⁻¹·mmHg⁻¹·L⁻¹; p = 0.038; d = 0.509) after the altitude camp were observed. During the acute hypoxia combined session, there were no changes in DL_CO after swimming training at 1850 m, but there was a decrease in DL_CO after cycling at a simulated altitude of 3000 m (40.6 ± 10.8 vs. 36.8 ± 11.2 mL·min⁻¹·mmHg⁻¹; p = 0.044; d = 0.341). A training camp at moderate altitude did not alter pulmonary diffusing capacity in elite swimmers, although a cycling session at a higher simulated altitude caused a certain degree of impairment of the alveolar–capillary gas exchange. Full article

Hantavirus cardiopulmonary syndrome (HCPS) is characterized by capillary leak, pulmonary edema (PE), and shock, which leads to death in up to 40% of patients. Treatment is supportive, including mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO). Hemodynamic monitoring is critical to titrate therapy and to decide ECMO support. Transpulmonary thermodilution (TPTD) provides hemodynamic and PE data that have not been systematically used to understand HCPS pathophysiology. We identified 11 HCPS patients monitored with TPTD: eight on MV, three required ECMO. We analyzed 133 measurements to describe the hemodynamic pattern and its association with PE. The main findings were reduced stroke volume, global ejection fraction (GEF), and preload parameters associated with increased extravascular lung water and pulmonary vascular permeability compatible with hypovolemia, myocardial dysfunction, and increased permeability PE. Lung water correlated positively with heart rate (HR, r = 0.20) and negatively with mean arterial pressure (r = −0.27) and GEF (r = −0.36), suggesting that PE is linked to hemodynamic impairment. Pulmonary vascular permeability correlated positively with HR (r = 0.31) and negatively with cardiac index (r = −0.49), end-diastolic volume (r = −0.48), and GEF (r = −0.40), suggesting that capillary leak contributes to hypovolemia and systolic dysfunction. In conclusion, TPTD data suggest that in HCPS patients, increased permeability leads to PE, hypovolemia, and circulatory impairment. Full article

Combined pulmonary fibrosis and emphysema (CPFE) has been increasingly recognized over the past 10–15 years as a clinical entity characterized by rather severe imaging and gas exchange abnormalities, but often only mild impairment in spirometric and lung volume indices. In this review, we explore the gas exchange and mechanical pathophysiologic abnormalities of pulmonary emphysema, pulmonary fibrosis, and combined emphysema and fibrosis with the goal of understanding how individual pathophysiologic observations in emphysema and fibrosis alone may impact clinical observations on pulmonary function testing (PFT) patterns in patients with CPFE. Lung elastance and lung compliance in patients with CPFE are likely intermediate between those of patients with emphysema and fibrosis alone, suggesting a counter-balancing effect of each individual process. The outcome of combined emphysema and fibrosis results in higher lung volumes overall on PFTs compared to patients with pulmonary fibrosis alone, and the forced expiratory volume in one second (FEV₁)/forced vital capacity (FVC) ratio in CPFE patients is generally preserved despite the presence of emphysema on chest computed tomography (CT) imaging. Conversely, there appears to be an additive deleterious effect on gas exchange properties of the lungs, reflecting a loss of normally functioning alveolar capillary units and effective surface area available for gas exchange, and manifested by a uniformly observed severe reduction in the diffusing capacity for carbon monoxide (D_LCO). Despite normal or only mildly impaired spirometric and lung volume indices, patients with CPFE are often severely functionally impaired with an overall rather poor prognosis. As chest CT imaging continues to be a frequent imaging modality in patients with cardiopulmonary disease, we expect that patients with a combination of pulmonary emphysema and pulmonary fibrosis will continue to be observed. Understanding the pathophysiology of this combined process and the abnormalities that manifest on PFT testing will likely be helpful to clinicians involved with the care of patients with CPFE. Full article