Cardiorespiratory and aerobic demands of squat exercise.

Squatting, a traditional resistance exercise classified as strength training, relies on anaerobic pathways, but its aerobic aspects remain unclear. We examined heart rate and oxygen demand during squats, exploring variations across different strength statuses. It fills gaps in understanding the cardiorespiratory effects of squatting, especially during multiple sets. Twenty-two young healthy resistance trained men (age: 28 ± 4 years) participated. Maximal oxygen consumption (V̇O2max) and 1 repetition maximum (RM) of squat were measured. Participants performed 5 sets of squat exercises at 65% of 1RM for 10 repetitions with 3-min rest intervals. Heart rate and pulmonary gas exchange were measured during the squat exercise. Participants were divided into high strength (HS; upper 50%) and low strength (LS; lower 50%) groups based on a median split of their 1 RM squat values (normalized to their body weight). During 5 sets of squat exercise, oxygen consumption (V̇O2) increased up to 47.8 ± 8.9 ml/kg/min, corresponding to 100.6% of predetermined V̇O2max. The HS group achieved a greater highest point of V̇O2 in relation to V̇O2max than the LS group (108.0 vs. 93.7%). During the exercise intervals, V̇O2 exceeded V̇CO2, while during the rest intervals, V̇CO2 surpassed V̇O2. Our findings suggest that the oxygen demand during squatting is notably substantial, which may vary according to the training status.

Altered glucose kinetics occurs with aging: a new outlook on metabolic flexibility.

Our purpose was to determine how age affects metabolic flexibility and underlying glucose kinetics in healthy young and older adults. Therefore, glucose and lactate tracers along with pulmonary gas exchange data were used to determine glucose kinetics and respiratory exchange ratios [RER = carbon dioxide production (V̇co2)/oxygen consumption (V̇o2)] during a 2-h 75-g oral glucose tolerance test (OGTT). After an 12-h overnight fast, 28 participants, 15 young (21-35 yr; 7 men and 8 women) and 13 older (60-80 yr; 7 men and 6 women), received venous primed-continuous infusions of [6,6-2H]glucose and [3-13C]lactate with a [Formula: see text] bolus. After a 90-min metabolic stabilization and tracer equilibration period, volunteers underwent an OGTT. Arterialized glucose concentrations ([glucose]) started to rise 15 min post glucose consumption, peaked at 60 min, and remained elevated. As assessed by rates of appearance (Ra) and disposal (Rd) and metabolic clearance rate (MCR), glucose kinetics were suppressed in older compared to young individuals. As well, unlike in young individuals, fractional gluconeogenesis (fGNG) remained elevated in the older population after the oral glucose challenge. Finally, there were no differences in 12-h fasting baseline or peak RER values following an oral glucose challenge in older compared to young men and women, making RER an incomplete measure of metabolic flexibility in the volunteers we evaluated. Our study revealed that glucose kinetics are significantly altered in a healthy aged population after a glucose challenge. Furthermore, those physiological deficits are not detected from changes in RER during an OGTT.NEW & NOTEWORTHY To determine metabolic flexibility in response to an OGTT, we studied healthy young and older men and women to determine glucose kinetics and changes in RER. Compared to young subjects, glucose kinetics were suppressed in older healthy individuals during an OGTT. Surprisingly, the age-related changes in glucose flux were not reflected in RER measurements; thus, RER measurements do not give a complete view of metabolic flexibility in healthy individuals.

Scaled-up Microfluidic Lung Assist Device for Artificial Placenta Application with High Gas Exchange Capacity.

Premature neonates with underdeveloped lungs experience respiratory issues and need respiratory support, such as mechanical ventilation or extracorporeal membrane oxygenation (ECMO). The "artificial placenta" (AP) is a noninvasive approach that supports their lungs and reduces respiratory distress, using a pumpless oxygenator connected to the systemic circulation, and can address some of the morbidity issues associated with ECMO. Over the past decade, microfluidic blood oxygenators have garnered significant interest for their ability to mimic physiological conditions and incorporate innovative biomimetic designs. Achieving sufficient gas transfer at a low enough pressure drop for a pumpless operation without requiring a large volume of blood to prime such an oxygenator has been the main challenge with microfluidic lung assist devices (LAD). In this study, we improved the gas exchange capacity of our microfluidic-based artificial placenta-type LAD while reducing its priming volume by using a modified fabrication process that can accommodate large-area thin film microfluidic blood oxygenator (MBO) fabrication with a very high gas exchange surface. Additionally, we demonstrate the effectiveness of a LAD assembled by using these scaled-up MBOs. The LAD based on our artificial placenta concept effectively increases oxygen saturation levels by 30% at a flow rate of 40 mL/min and a pressure drop of 23 mmHg in room air, which is sufficient to support partial oxygenation for 1 kg preterm neonates in respiratory distress. When the gas ambient environment was changed to pure oxygen at atmospheric pressure, the LAD would be able to support premature neonates weighing up to 2 kg. Furthermore, our experiments reveal that the LAD can handle high blood flow rates of up to 150 mL/min and increase oxygen saturation levels by ∼20%, which is equal to an oxygen transfer of 7.48 mL/min in an enriched oxygen environment and among the highest for microfluidic AP type devices. Such performance makes this LAD suitable for providing essential support to 1-2 kg neonates in respiratory distress.

Acute physiological responses of blood flow restriction between high-intensity interval repetitions in trained cyclists.

Blood flow restriction (BFR) is increasingly being used to enhance aerobic performance in endurance athletes. This study examined physiological responses to BFR applied in recovery phases within a high-intensity interval training (HIIT) session in trained cyclists. Eleven competitive road cyclists (mean ± SD, age: 28 ± 7 years, body mass: 69 ± 6 kg, peak oxygen uptake: 65 ± 9 mL · kg-1 · min-1) completed two randomised crossover conditions: HIIT with (BFR) and without (CON) BFR applied during recovery phases. HIIT consisted of six 30-s cycling bouts at an intensity equivalent to 85% of maximal 30-s power (523 ± 93 W), interspersed with 4.5-min recovery. BFR (200 mmHg, 12 cm cuff width) was applied for 2-min in the early recovery phase between each interval. Pulmonary gas exchange (V̇O2, V̇CO2, and V̇E), tissue oxygen saturation index (TSI), heart rate (HR), and serum vascular endothelial growth factor concentration (VEGF) were measured. Compared to CON, BFR increased V̇CO2 and V̇E during work bouts (both p < 0.05, dz < 0.5), but there was no effect on V̇O2, TSI, or HR (p > 0.05). In early recovery, BFR decreased TSI, V̇O2, V̇CO2, and V̇E (all p < 0.05, dz > 0.8) versus CON, with no change in HR (p > 0.05). In late recovery, when BFR was released, V̇O2, V̇CO2, V̇E, and HR increased, but TSI decreased versus CON (all p < 0.05, dz > 0.8). There was a greater increase in VEGF at 3-h post-exercise in BFR compared to CON (p < 0.05, dz > 0.8). Incorporating BFR into HIIT recovery phases altered physiological responses compared to exercise alone.

Pulmonary gas exchange and ventilatory efficiency during exercise in health and diseases.

INTRODUCTION: Cardiopulmonary exercise testing (CPET) is nowadays used to study the exercise response in healthy subjects and in disease. Ventilatory efficiency is one of the main determinants in exercise tolerance, and its main variables are a useful tool to guide pathophysiologists toward specific diagnostic pathways, providing prognostic information and improving disease management, treatment, and outcomes. AREAS COVERED: This review will be based on today's available scientific evidence, describing the main physiological determinants of ventilatory efficiency at rest and during exercise, and focusing also on how CPET variables are modified in specific diseases, leading to the possibility of early diagnosis and management. EXPERT OPINION: Growing knowledge on CPET interpretation and a wider use of this clinical tool is expected in order to offer more precise diagnostic and prognostic information to patients and clinicians, helping in the management of therapeutic decisions. Future research could be able to identify new and more simple markers of ventilatory efficiency, and to individuate new interventions for the improvement of symptoms, such as exertional dyspnea.

Effects of extracorporeal CO2 removal on gas exchange and ventilator settings: a systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis to evaluate the impact of extracorporeal carbon dioxide removal (ECCO2R) on gas exchange and respiratory settings in critically ill adults with respiratory failure. METHODS: We conducted a comprehensive database search, including observational studies and randomized controlled trials (RCTs) from January 2000 to March 2022, targeting adult ICU patients undergoing ECCO2R. Primary outcomes were changes in gas exchange and ventilator settings 24 h after ECCO2R initiation, estimated as mean of differences, or proportions for adverse events (AEs); with subgroup analyses for disease indication and technology. Across RCTs, we assessed mortality, length of stay, ventilation days, and AEs as mean differences or odds ratios. RESULTS: A total of 49 studies encompassing 1672 patients were included. ECCO2R was associated with a significant decrease in PaCO2, plateau pressure, and tidal volume and an increase in pH across all patient groups, at an overall 19% adverse event rate. In ARDS and lung transplant patients, the PaO2/FiO2 ratio increased significantly while ventilator settings were variable. "Higher extraction" systems reduced PaCO2 and respiratory rate more efficiently. The three available RCTs did not demonstrate an effect on mortality, but a significantly longer ICU and hospital stay associated with ECCO2R. CONCLUSIONS: ECCO2R effectively reduces PaCO2 and acidosis allowing for less invasive ventilation. "Higher extraction" systems may be more efficient to achieve this goal. However, as RCTs have not shown a mortality benefit but increase AEs, ECCO2R's effects on clinical outcome remain unclear. Future studies should target patient groups that may benefit from ECCO2R. PROSPERO Registration No: CRD 42020154110 (on January 24, 2021).

The alveolus: Our current knowledge of how the gas exchange unit of the lung is constructed and repaired.

The mammalian lung completes its last step of development, alveologenesis, to generate sufficient surface area for gas exchange. In this process, multiple cell types that include alveolar epithelial cells, endothelial cells, and fibroblasts undergo coordinated cell proliferation, cell migration and/or contraction, cell shape changes, and cell-cell and cell-matrix interactions to produce the gas exchange unit: the alveolus. Full functioning of alveoli also involves immune cells and the lymphatic and autonomic nervous system. With the advent of lineage tracing, conditional gene inactivation, transcriptome analysis, live imaging, and lung organoids, our molecular understanding of alveologenesis has advanced significantly. In this review, we summarize the current knowledge of the constituents of the alveolus and the molecular pathways that control alveolar formation. We also discuss how insight into alveolar formation may inform us of alveolar repair/regeneration mechanisms following lung injury and the pathogenic processes that lead to loss of alveoli or tissue fibrosis.

The Effect of Recruitment Maneuver on Static Lung Compliance in Patients Undergoing General Anesthesia for Laparoscopic Cholecystectomy: A Single-Centre Prospective Clinical Intervention Study.

Background and Objectives: The aim of this study was to examine whether the use of an alveolar recruitment maneuver (RM) leads to a significant increase in static lung compliance (Cstat) and an improvement in gas exchange in patients undergoing laparoscopic cholecystectomy. Material and Methods: A clinical prospective intervention study was conducted. Patients were divided into two groups according to their body mass index (BMI): normal-weight (group I) and pre-obese and obese grade I (group II). Lung mechanics were monitored (Cstat, dynamic compliance-Cdin, peak pressure-Ppeak, plateau pressure-Pplat, driving pressure-DP) alongside gas exchange, and hemodynamic changes (heart rate-HR, mean arterial pressure-MAP) at six time points: T1 (induction of anesthesia), T2 (formation of pneumoperitoneum), T3 (RM with a PEEP of 5 cm H2O), T4 (RM with a PEEP of 7 cm H2O), T5 (desufflation), and T6 (RM at the end). The RM was performed by increasing the peak pressure by +5 cm of H2O at an equal inspiration-to-expiration ratio (I/E = 1:1) and applying a PEEP of 5 and 7 cm of H2O. Results: Out of 96 patients, 33 belonged to group I and 63 to group II. An increase in Cstat values occurred after all three RMs. At each time point, the Cstat value was measured higher in group I than in group II. A higher increase in Cstat was observed in group II after the second and third RM. Cstat values were higher at the end of the surgical procedure compared to values after the induction of anesthesia. The RM led to a significant increase in PaO2 in both groups without changes in HR or MAP. Conclusions: During laparoscopic cholecystectomy, the application of RM leads to a significant increase in Cstat and an improvement in gas exchange. The prevention of atelectasis during anesthesia should be initiated immediately after the induction of anesthesia, using protective mechanical ventilation and RM.

Effects of Positive End-expiratory Pressure on Pulmonary Perfusion Distribution and Intrapulmonary Shunt during One-lung Ventilation in Pigs: A Randomized Crossover Study.

BACKGROUND: During one-lung ventilation (OLV), positive end-expiratory pressure (PEEP) can improve lung aeration but might overdistend lung units and increase intrapulmonary shunt. The authors hypothesized that higher PEEP shifts pulmonary perfusion from the ventilated to the nonventilated lung, resulting in a U-shaped relationship with intrapulmonary shunt during OLV. METHODS: In nine anesthetized female pigs, a thoracotomy was performed and intravenous lipopolysaccharide infused to mimic the inflammatory response of thoracic surgery. Animals underwent OLV in supine position with PEEP of 0 cm H2O, 5 cm H2O, titrated to best respiratory system compliance, and 15 cm H2O (PEEP0, PEEP5, PEEPtitr, and PEEP15, respectively, 45 min each, Latin square sequence). Respiratory, hemodynamic, and gas exchange variables were measured. The distributions of perfusion and ventilation were determined by IV fluorescent microspheres and computed tomography, respectively. RESULTS: Compared to two-lung ventilation, the driving pressure increased with OLV, irrespective of the PEEP level. During OLV, cardiac output was lower at PEEP15 (5.5 ± 1.5 l/min) than PEEP0 (7.6 ± 3 l/min) and PEEP5 (7.4 ± 2.9 l/min; P = 0.004), while the intrapulmonary shunt was highest at PEEP0 (PEEP0: 48.1% ± 14.4%; PEEP5: 42.4% ± 14.8%; PEEPtitr: 37.8% ± 11.0%; PEEP15: 39.0% ± 10.7%; P = 0.027). The relative perfusion of the ventilated lung did not differ among PEEP levels (PEEP0: 65.0% ± 10.6%; PEEP5: 68.7% ± 8.7%; PEEPtitr: 68.2% ± 10.5%; PEEP15: 58.4% ± 12.8%; P = 0.096), but the centers of relative perfusion and ventilation in the ventilated lung shifted from ventral to dorsal and from cranial to caudal zones with increasing PEEP. CONCLUSIONS: In this experimental model of thoracic surgery, higher PEEP during OLV did not shift the perfusion from the ventilated to the nonventilated lung, thus not increasing intrapulmonary shunt.

Hemodynamic, ventilatory and gas exchange responses to exercise using a cycle ergometer and the incremental shuttle walk test in pregnant women.

BACKGROUND: Cardiovascular disease, including hypertension, in pregnant women is a leading cause of morbidity and mortality globally. The development of reference intervals for cardiovascular responses using exercising testing to measure oxygen utilisation (V̇O2) with cardiopulmonary exercise testing (CPET), and distances walked using the incremental shuttle walk test (ISWT), may be promising methods to assess and stratify pregnant women regarding their risk of adverse pregnancy outcomes, to encourage exercise during pregnancy, and to improve exercise prescriptions during pregnancy. We aimed to determine the reference intervals for V̇O2 at rest, anaerobic threshold (AT), and submaximal exercise using CPET, and the reference interval for the ISWT, to develop a correlation equitation that predicts submaximal V̇O2 from the distance walked in the ISWT, and to explore the relationship between hemoglobin (Hb) and ferritin concentration and V̇O2 at AT in women in second trimester. METHODS: After prospective IRB approval (HREC 15/23) and clinical trials registration (ANZCTR ACTRN12615000964516), and informed written consent, we conducted CPET and the ISWT according to international guidelines in a university associated tertiary referral obstetric and adult medicine hospital, in healthy pregnant women in second trimester (14 to 27 gestational weeks). Hemoglobin and ferritin concentrations were recorded from pathology results in the participants' medical records at the time of exercise testing. Adverse events were recorded. RESULTS: About 90 participants undertook CPET, 28 of which also completed the ISWT. The mean ± SD age and body mass index (BMI) were 32 ± 3.2 years, and 25 ± 2.7 kg/m2. Median (IQR) gestation was 23 (22-24) weeks. One in 4 women were 24 weeks or greater gestation. The reference intervals for V̇O2 at rest, AT, and submaximal exercise were 2.9 to 5.3, 8.1 to 20.7, and 14.1 to 30.5 mL/kg/min respectively. The reference interval for the ISWT was 218 to 1058 meters. The correlation equation to predict submaximal V̇O2 from the distance walked in the ISWT was submaximal V̇O2 (mL/kg/min) = 0.012*distance walked in ISWT (m) + 14.7 (95%CI slope 0.005-0.070, Pearson r = 0.5426 95%CI 0.2126-0.7615, P = .0029). Hemoglobin concentration was positively correlated with V̇O2 at AT (AT V̇O2 (mL/kg/min) = 0.08*Hb (g/L) + 4.9 (95%CI slope 0.0791-0.143, Pearson r = 0.2538 95%CI 0.049-0.438, P = .016). There was no linear association between ferritin and submaximal V̇O2 (Pearson r = 0.431 P = .697). There were no maternal or fetal complications. CONCLUSIONS: CPET and ISWT are safe and feasible in women in second trimester including those at or beyond 24 weeks gestation. We have established the reference interval for V̇O2 at rest, AT, and submaximal exercise by CPET, the reference interval for the distance walked for the ISWT, and a correlation equation to predict submaximal V̇O2 for use in clinical practice and research. Hemoglobin rather than ferritin is likely correlated with exercise capacity in pregnancy suggesting vigilance to correct lower hemoglobin levels may positively impact maternal health. CLINICAL TRIALS REGISTRY: The study was prospectively registered with the Australian and New Zealand Clinical Date of registration - 15/9/2015; Date of initial participant enrolment - 4/11/2015; Clinical trial identification number; ACTRN12615000964516; URL of the registration site - https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369216.

Limiting Overdistention or Collapse When Mechanically Ventilating Injured Lungs: A Randomized Study in a Porcine Model.

Rationale: It is unknown whether preventing overdistention or collapse is more important when titrating positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). Objectives: To compare PEEP targeting minimal overdistention or minimal collapse or using a compromise between collapse and overdistention in a randomized trial and to assess the impact on respiratory mechanics, gas exchange, inflammation, and hemodynamics. Methods: In a porcine model of ARDS, lung collapse and overdistention were estimated using electrical impedance tomography during a decremental PEEP titration. Pigs were randomized to three groups and ventilated for 12 hours: PEEP set at ⩽3% of overdistention (low overdistention), ⩽3% of collapse (low collapse), and the crossing point of collapse and overdistention. Measurements and Main Results: Thirty-six pigs (12 per group) were included. Median (interquartile range) values of PEEP were 7 (6-8), 11 (10-11), and 15 (12-16) cm H2O in the three groups (P < 0.001). With low overdistension, 6 (50%) pigs died, whereas survival was 100% in both other groups. Cause of death was hemodynamic in nature, with high transpulmonary vascular gradient and high epinephrine requirements. Compared with the other groups, pigs surviving with low overdistension had worse respiratory mechanics and gas exchange during the entire protocol. Minimal differences existed between crossing-point and low-collapse animals in physiological parameters, but postmortem alveolar density was more homogeneous in the crossing-point group. Inflammatory markers were not significantly different. Conclusions: PEEP to minimize overdistention resulted in high mortality in an animal model of ARDS. Minimizing collapse or choosing a compromise between collapse and overdistention may result in less lung injury, with potential benefits of the compromise approach.

Gas exchange parameters for the prediction of obstructive sleep apnea in infants.

STUDY OBJECTIVES: Sleep laboratory polysomnography is the gold standard for obstructive sleep apnea (OSA) diagnosis in infants, but its access remains limited. Oximetry-capnography is another simple and widely used tool that can provide information on the presence of desaturations and alveolar hypoventilation. However, its reliability is debated. This study aimed at examining its use in determining OSA severity in infants. METHODS: This retrospective study was conducted in a sleep unit in a tertiary hospital in infants < 4 months old with clinical signs of OSA or Pierre Robin sequence who underwent a 1-night polysomnography coupled with oximetry-capnography. RESULTS: Among the 78 infants included (median [interquartile range] age: 61 [45-89] days at polysomnography), 44 presented with Pierre Robin sequence and 34 presented with isolated airway obstruction. The clinical, sleep, and respiratory characteristics were not significantly different between the 2 subgroups. In the entire cohort, 63.5% had severe OSA. The median obstructive apnea-hypopnea index was 14.5 (7.4-5.9) events/h, peripheral oxygen saturation (SpO2) was 97.4% (96.5-98.1%), and transcutaneous carbon dioxide pressure (PtcCO2) was 41.1 mmHg (38.3-44.9). The optimal threshold to predict an obstructive apnea-hypopnea index > 10 events/h was 6 events/h for an oxygen desaturation index ≥ 3% (sensitivity, 95.7%; specificity, 51.9%) and 2 events/h for an oxygen desaturation index ≥ 4% (sensitivity, 95.7%; specificity, 48.1%). CONCLUSIONS: Whereas transcutaneous capnography does not appear to be sufficient in predicting severe OSA in infants < 4 months old with Pierre Robin sequence or clinical signs of OSA, oximetry may be a useful alternative for the screening of severe OSA in infants in the absence of polysomnography. CITATION: Gyapay R, Ioan I, Thieux M, et al. Gas exchange parameters for the prediction of obstructive sleep apnea in infants. J Clin Sleep Med. 2024;20(7):1059-1067.

Heart Rate Variability Thresholds: Agreement with Established Approaches and Reproducibility in Trained Females and Males.

PURPOSE: To determine in trained females and males i) the agreement between the gas exchange threshold (GET), lactate threshold 1 (LT1), and heart rate variability threshold 1 (HRVT1), as well as between the respiratory compensation point (RCP), lactate threshold 2 (LT2), and heart rate variability threshold 2 (HRVT2), and ii) the reproducibility of HRVT1 and HRVT2 during 2-min incremental step protocols. METHODS: Fifty-seven trained participants (24 females) completed a 2-min step incremental test to task failure. Nineteen participants (eight females) completed a second test to evaluate reproducibility. Gas exchange and ventilatory responses, blood lactate concentration, and RR time series were recorded to assess the oxygen consumption (V̇O 2 ) and heart rate (HR) associated with the GET, RCP, LT1, LT2, HRVT1, and HRVT2. RESULTS: V̇O 2 -GET versus V̇O 2 -HRVT1 and HR-GET versus HR-HRVT1 were statistically different for females (29.5 ± 4.0 vs 34.6 ± 6.1 mL·kg -1 ·min -1 ; 154 ± 11 vs 166 ± 12 bpm) and for males (33.9 ± 4.2 vs 42.7 ± 4.6 mL·kg -1 ·min -1 ; 145 ± 11 vs 165 ± 9 bpm; P < 0.001). V̇O 2 and HR at HRVT1 were greater than at LT1 ( P < 0.05). V̇O 2 -RCP versus V̇O 2 -HRVT2 and HR-RCP versus HR-HRVT2 were not statistically different for females (40.1 ± 4.7 vs 39.5 ± 6.7 mL·kg -1 ·min -1 ; 177 ± 9 vs 176 ± 9 bpm) and males (48.4 ± 5.4 vs 47.8 ± 4.8 mL·kg -1 ·min -1 ; 176 ± 8 vs 175 ± 9 bpm; P > 0.05). V̇O 2 and HR responses at LT2 were similar to HRVT2 ( P > 0.05). Intraclass correlation coefficient for V̇O 2 -HRVT1, HR-HRVT1, V̇O 2 -HRVT2, and HR-HRVT2 indicated good reproducibility when comparing the two different time points to standard methods. CONCLUSIONS: Whereas HRVT2 is a valid and reproducible estimate of the RCP/LT2, current approaches for HRVT1 estimation did not show good agreement with outcomes at GET and LT1.

Toward 3D printed microfluidic artificial lungs for respiratory support.

Microfluidic artificial lungs (µALs) are a new class of membrane oxygenators. Compared to traditional hollow-fiber oxygenators, µALs closely mimic the alveolar microenvironment due to their size-scale and promise improved gas exchange efficiency, hemocompatibility, biomimetic blood flow networks, and physiologically relevant blood vessel pressures and shear stresses. Clinical translation of µALs has been stalled by restrictive microfabrication techniques that limit potential artificial lung geometries, overall device size, and throughput. To address these limitations, a high-resolution Asiga MAX X27 UV digital light processing (DLP) 3D printer and custom photopolymerizable polydimethylsiloxane (PDMS) resin were used to rapidly manufacture small-scale µALs via vat photopolymerization (VPP). Devices were designed in SOLIDWORKS with 500 blood channels and 252 gas channels, where gas and blood flow channels were oriented orthogonally and separated by membranes on the top and bottom, permitting two-sided gas exchange. Successful devices were post-processed to remove uncured resin from microchannels and assembled with external tubing in preparation for gas exchange performance testing with ovine whole blood. 3D printed channel dimensions were 172 µm-tall × 320 µm-wide, with 62 µm-thick membranes and 124 µm-wide support columns. Measured outlet blood oxygen saturation (SO2) agreed with theoretical models and rated flow of the device was 1 mL min-1. Blood side pressure drop was 1.58 mmHg at rated flow. This work presents the highest density of 3D printed microchannels in a single device, one of the highest CO2 transfer efficiencies of any artificial lung to date, and a promising approach to translate µALs one step closer to the clinic.

Signal Variability Comparative Analysis of Healthy Early- and Late-Pubertal Children during Cardiopulmonary Exercise Testing.

PURPOSE: The kinetics of physiological responses to exercise have traditionally been characterized by estimating exponential equation parameters using iterative best-fit techniques of heart rate (HR) and gas exchange (respiratory rate, oxygen uptake (V̇O 2 ), carbon dioxide output, and ventilation). In this study, we present a novel approach to characterizing the maturation of physiological responses to exercise in children by accounting for response uncertainty and variability. METHODS: Thirty-seven early-pubertal (17 females, 20 males) and 44 late-pubertal (25 females, 19 males) participants performed three multiple brief exercise bouts (MBEB). MBEB consisted of ten 2-min bouts of cycle ergometry at constant work rate interspersed by 1-min rest. Exercise intensity was categorized as low, moderate, or high, corresponding to 40%, 60%, and 80% of peak work rate, and performed in random order on 3 separate days. We evaluated sample entropy (SampEn), approximate entropy, detrended fluctuation analysis, and average absolute local variability of HR and gas exchange. RESULTS: SampEn of HR and gas-exchange responses to MBEB was greater in early- compared with late-pubertal participants (e.g., V̇O 2 early-pubertal vs late-pubertal, 1.70 ± 0.023 vs 1.41 ± 0.027; P = 2.97 × 10 -14 ), and decreased as MBEB intensity increased (e.g., 0.37 ± 0.01 HR for low-intensity compared with 0.21 ± 0.014 for high intensity, P = 3.56 × 10 -17 ). Females tended to have higher SampEn than males (e.g., 1.61 ± 0.025 V̇O 2 for females vs 1.46 ± 0.031 for males, P = 1.28 × 10 -4 ). Average absolute local variability was higher in younger participants for both gas exchange and HR (e.g., early-pubertal vs late-pubertal V̇O 2 , 17.48 % ± 0.56% vs 10.24 % ± 0.34%; P = 1.18 × 10 -21 ). CONCLUSIONS: The greater entropy in signal response to a known, quantifiable exercise perturbation in the younger children might represent maturation-dependent, enhanced competition among physiological controlling mechanisms that originate at the autonomic, subconscious, and cognitive levels.

The algorithm used for the calculation of gas exchange affects the estimation of O2 uptake kinetics at the onset of moderate-intensity exercise.

At the start of a moderate-intensity square-wave exercise, after a short delay, breath-by-breath O2 uptake at the mouth is approximated to a mono-exponential function, whose time constant is considered matched to that of the O2 uptake of the working muscles. We compared the kinetic parameters obtained from the breath-by-breath gas exchange data yielded by the 'Independent-breath' algorithm (IND), which accounts for the changes in lung gas stores, with those obtained with the classical 'Expiration-only' algorithm (EXP). The two algorithms were applied on the same flow and gas fraction traces acquired on 10 healthy volunteers, performing 10 times the same moderate-intensity exercise transition. Repeated O2 uptake responses were stacked together and the kinetic parameters of a mono-exponential function were estimated by non-linear regression, removing the data pertaining to 1-s progressively longer initial periods (ΔTr ). Independently of ΔTr , the mean response time (time constant + time delay) obtained for the IND data was faster compared to the EXP data (∼43 s vs. ∼47 s, P < 0.001), essentially because of shorter time delays. Between ΔTr  = 16 s and ΔTr  = 29s, the time constants of the IND data decreased (30.7 s vs. 28.0 s, P < 0.05; drop = 10%), but less than those of the EXP data (32.2 s vs. 26.2 s, P < 0.001; drop = 23%); with the same ΔTr , the time constants of the two algorithms' data were not different (P > 0.07). The different decrease in the time constant, together with the different mean response time, suggests that the data yielded by the two algorithms provide a different picture of the phenomena occurring at the beginning of the exercise.