Pulmonary Ventilation Research Articles

PECULIARITIES OF PULMONARY VENTILATION RESPONSE TO DOSED HYPOXIA IN ELDERLY PEOPLE WITH IMPAIRED GLUCOSE TOLERANCE.

The aim: To determine the peculiarities of the response of pulmonary ventilation to hypoxia in elderly people with impaired glucose tolerance. Materials and methods: Forty-three elderly people were examined, including 20 patients with impaired glucose tolerance and 23 healthy individuals with preserved glucose tolerance. Fasting plasma glucose and insulin concentrations were determined, and the HOMA-IR insulin resistance index was calculated. Under conditions of normoxia and during a dosed hypoxic test (12% oxygen, duration 20 min), blood saturation and lung ventilation parameters were monitored. Results: Under conditions of normoxia, the indicators of lung ventilation function did not differ between the groups of elderly people with impaired and preserved glucose tolerance. Under conditions of hypoxia, elderly people with impaired glucose tolerance had a less significant increase in ventilation, despite the development of more severe arterial hypoxemia. This leads to a decrease in the ventilatory response to hypoxia in case of impaired carbohydrate metabolism. Conclusions: In people with impaired glucose tolerance, a less significant ventilatory response to hypoxia is combined with more pronounced insulin resistance.

Pathophysiology and Clinical Meaning of Ventilation-Perfusion Mismatch in the Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) remains an important clinical challenge with a mortality rate of 35-45%. It is being increasingly demonstrated that the improvement of outcomes requires a tailored, individualized approach to therapy, guided by a detailed understanding of each patient's pathophysiology. In patients with ARDS, disturbances in the physiological matching of alveolar ventilation (V) and pulmonary perfusion (Q) (V/Q mismatch) are a hallmark derangement. The perfusion of collapsed or consolidated lung units gives rise to intrapulmonary shunting and arterial hypoxemia, whereas the ventilation of non-perfused lung zones increases physiological dead-space, which potentially necessitates increased ventilation to avoid hypercapnia. Beyond its impact on gas exchange, V/Q mismatch is a predictor of adverse outcomes in patients with ARDS; more recently, its role in ventilation-induced lung injury and worsening lung edema has been described. Innovations in bedside imaging technologies such as electrical impedance tomography readily allow clinicians to determine the regional distributions of V and Q, as well as the adequacy of their matching, providing new insights into the phenotyping, prognostication, and clinical management of patients with ARDS. The purpose of this review is to discuss the pathophysiology, identification, consequences, and treatment of V/Q mismatch in the setting of ARDS, employing experimental data from clinical and preclinical studies as support.

Respiratory Muscle Interval Training Improves Exercise Capacity in Obese Adolescents during a 3-Week In-Hospital Multidisciplinary Body Weight Reduction Program.

The purpose of this study was to determine whether a novel approach of interval training targeted to the respiratory muscles (RMIT; normocapnic hyperpnea with resistance) in addition to a multidisciplinary in-hospital body weight reduction program (BWRP) was able to improve the integrative response to exercise in young patients with obesity. Nine male patients (17.9 ± 4.9 (x ± SD) years; 113.8 ± 16.3 kg) underwent 12 sessions of RMIT and eight age-and sex-matched patients underwent 12 sessions of a sham protocol (CTRL) during the same 3-week BWRP. Before and after the interventions the patients performed an incremental and a heavy-intensity constant work-rate (CWR>GET) cycling exercise to voluntary exhaustion. Body mass decreased by ~4.0 kg after both RMIT (p = 0.0001) and CTRL (p = 0.0002). Peak pulmonary O2 uptake (V˙O2) increased after RMIT (p = 0.02) and CTRL (p = 0.0007). During CWR>GET at ISO-time, V˙O2 (p = 0.0007), pulmonary ventilation (p = 0.01), heart rate (p = 0.02), perceived respiratory discomfort (RPER; p = 0.03) and leg effort (p = 0.0003) decreased after RMIT; only RPER (p = 0.03) decreased after CTRL. Time to exhaustion increased after RMIT (p = 0.0003) but not after CTRL. In young patients with obesity, RMIT inserted in a 3-week BWRP reduced the cardiorespiratory burden, the metabolic cost, the perceived effort, and improved exercise tolerance during heavy-intensity cycling.

Quantitative end-tidal carbon dioxide at initiation of resuscitation may help guide the ventilation of infants born at less than 30 weeks gestation.

Estimation of end-tidal carbon dioxide (EtCO2 ) with capnography can guide mask ventilation in infants born at less than 30 weeks of gestation. Chemical-sensitive colorimetric devices to detect CO2 are widely used at resuscitation. We aimed to quantify EtCO2 in the first breaths following initiation of mask ventilation at birth and correlated need for endotracheal intubation. Infants <30 weeks gestation receiving mask ventilation were randomised into two groups of mask-hold technique (one-person vs. two-person). Data on EtCO2 in the first 30 breaths, time to achieve 5 mmHg, 10 mmHg and 15 mmHg CO2 using a respiratory function monitor was determined. Twenty-five infants with a mean gestation of 27.3 (±3 weeks) and mean birth weight 920.4 (±188.3g) were analysed. The median EtCO2 was 5.6 mmHg in the first 10 breaths, whereas it was 12.6 mmHg for 11-20 breaths and 18 mmHg for 21-30 breaths. There was no significant difference in maximum median EtCO2 for the first 20 breaths, although EtCO2 was significantly lower in infants who were intubated (32.0 vs. 15.0, p=0.018). EtCO2 monitoring in infants <30 weeks gestation at birth is feasible and reflective of alveolar ventilation. EtCO2 may help guide ventilation of preterm infants at birth.

Association between maximal aerobic capacity and heart rate variability

Relevance. Сardiovascular status could be assessed by maximal aerobic capacity (VO2max) through direct analysis of the gases involved in pulmonary ventilation and monitoring fluctuations in intervals between beats over time as heart rate variability. The aim of the study was to investigate the relationship between VO2max and heart rate variability in young adults. Materials and Methods. A total of 100 young adults between the ages of 18 and 25 were included in observational study, who did not engage in any strenuous physical activity, 50 of whom were male and 50 of whom were female.There were measured Heart rate variability in the frequency domain; LF, HF, LF/HF, and time domain; SDNN, RMSSD, pNN 50, and VO2max were assessed using a treadmill test according to Graded Exercise Protocol. Results and Discussion. There was weak positive correlation of VO2max with LF ( r = 0.177) and weak negative correlation with HF ( r = -0.141). Male participants had a weak negative relationship between VO2 max and LF ( r = -0.075), whereas female respondents had a weak positive relationship(r = 0.286). There was weak negative correlation of VO2max with LF/HF ratio for male subjects but weak positive correlation ( r = -0.101) for female subjects. For male and female participants, there was a weak negative association of VO2max with SDNN ( r = -0.170) and ( r = -0.301), respectively. Male and female participants had a weak negative association of VO2max with RMSSD, with ( r = -0.154) and ( r = -0.284) respectively. Male and female participants had a slight negative association of VO2max with pNN 50, with ( r = -0.062) and ( r = -0.441) respectively. Conclusion. Significant variations were found in the time domain and frequency domain indices including HF and LF/HF ratio which represents the balance between sympathetic and parasympathetic responses.

Competencies in Basic Life Support after a Course with or without Rescue Ventilation: Historical Cohort Study.

Simplifying the international guidelines to improve skills after training and their retention over time has been one of the top priorities in recent years. The objective of our study was to compare the results of the practical skills learned during training in basic life support with and without pulmonary ventilation. This was a comparative study of historical cohorts consisting of undergraduate students in health sciences. In one cohort, rescue breathing was performed, and in the other, it was not. The same data collection instruments were used for both cohorts: a test type examination of knowledge, data from a smart mannequin and an instructor observation grid. The means of knowledge and practical skills scores collected by the mannequin were compared using independent sample t-tests. 497 students were recruited without significant differences between the two cohorts. The mean scores for knowledge and skills determined by the instructor and the mannequin were statistically higher in the cohort that did not perform rescue breathing. Students who participated in basic life support training that did not include rescue breathing scored better than those who participated in training that included this skill. Training with only compressions simplifies the guidelines and increases learning and content retention.

COVID-19 and athletes: Endurance sport and activity resilience study-CAESAR study.

Background: The COVID-19 pandemic and imposed restrictions influenced athletic societies, although current knowledge about mild COVID-19 consequences on cardiopulmonary and physiologic parameters remains inconclusive. This study aimed to assess the impact of mild COVID-19 inflection on cardiopulmonary exercise test (CPET) performance among endurance athletes (EA) with varied fitness level. Materials and Methods: 49 EA (nmale = 43, nfemale = 6, mean age = 39.94 ± 7.80yr, height = 178.45cm, weight = 76.62kg; BMI = 24.03kgm-2) underwent double treadmill or cycle ergometer CPET and body analysis (BA) pre- and post-mild COVID-19 infection. Mild infection was defined as: (1) without hospitalization and (2) without prolonged health complications lasting for >14days. Speed, power, heart rate (HR), oxygen uptake (VO2), pulmonary ventilation, blood lactate concentration (at the anaerobic threshold (AT)), respiratory compensation point (RCP), and maximum exertion were measured before and after COVID-19 infection. Pearson's and Spearman's r correlation coefficients and Student t-test were applied to assess relationship between physiologic or exercise variables and time. Results: The anthropometric measurements did not differ significantly before and after COVID-19. There was a significant reduction in VO2 at the AT and RCP (both p < 0.001). Pre-COVID-19 VO2 was 34.97 ± 6.43mlkg·min-1, 43.88 ± 7.31mlkg·min-1 and 47.81 ± 7.81mlkg·min-1 respectively for AT, RCP and maximal and post-COVID-19 VO2 was 32.35 ± 5.93mlkg·min-1, 40.49 ± 6.63mlkg·min-1 and 44.97 ± 7.00mlkg·min-1 respectively for AT, RCP and maximal. Differences of HR at AT (p < 0.001) and RCP (p < 0.001) was observed. The HR before infection was 145.08 ± 10.82bpm for AT and 168.78 ± 9.01bpm for RCP and HR after infection was 141.12 ± 9.99bpm for AT and 165.14 ± 9.74bpm for RCP. Time-adjusted measures showed significance for body fat (r = 0.46, p < 0.001), fat mass (r = 0.33, p = 0.020), cycling power at the AT (r = -0.29, p = 0.045), and HR at RCP (r = -0.30, p = 0.036). Conclusion: A mild COVID-19 infection resulted in a decrease in EA's CPET performance. The most significant changes were observed for VO2 and HR. Medical Professionals and Training Specialists should be aware of the consequences of a mild COVID-19 infection in order to recommend optimal therapeutic methods and properly adjust the intensity of training.

970: PHYSIOLOGY-BASED VENTILATOR COMPUTER DECISION SUPPORT OUTPERFORMS CLINICIANS IN AN IN SILICO TRIAL

Introduction: Intensivists are routinely required to titrate alveolar minute ventilation based on blood gas information. Survey data show that intensive care trainees feel insufficiently trained in ventilator management. Bedside decision support has the potential to facilitate more efficient ventilator titration and serve as a teaching tool for trainees. Methods: We developed an online ventilator calculator based upon arterial partial pressure of carbon dioxide (PaCO2) and Henderson-Hasselbalch equations, allowing clinicians to input ventilator parameters as well as current and desired blood gas information. We validated predictions among arterial blood gas (ABG) values from a single quaternary academic pediatric intensive care unit (PICU). We included all ABG values obtained between 1/1/2010 and 12/31/2020 among PICU patients receiving invasive pressure control, volume control, or volume targeted ventilation and concurrent pharmacologic muscle relaxation with a repeat blood gas analysis within 1-24 hours. We excluded ABGs from patients on extracorporeal support. We subsequently performed a retrospective in-silico trial on a subset of ABGs meeting criteria for ventilator weaning (pCO2 < 30 and pH > 7.35 or pCO2 < 50 and pH > 7.50) or escalation (pCO2 > 50 and pH < 7.30 or pCO2 > 45 and pH < 7.20), excluding patients with traumatic brain injury. Clinician behavior was compared against calculator recommendations, with a goal of achieving an ABG value that met neither weaning nor escalation criteria. Results: There were 16,835 included ABGs among 664 patients, with a median (IQR) time between ABGs of 3.8 (2.2-4.4) hours. The median (IQR) difference between predicted and actual PaCO2 values was 0.00 (-3.06-3.00) mmHg. 11,460/16,835 (68.1%) PaCO2 values were within 5 mmHg of predicted, and 14,902/16,835 (88.5%) were within 10 mmHg. There were 2,433 ABGs among 350 patients included in the in-silico trial. Calculator recommendations were preferable to clinician behavior in 1,149/1,534 (74.9%) weaning scenarios and 605/899 (67.3%) escalation scenarios. Conclusions: Computer decision support outperformed clinician actions in this retrospective in-silico trial and may provide a useful teaching tool for trainees. Prospective study is needed to determine feasibility and user satisfaction.

Complex ventilation problems with no simple solution

Daoud and Franck in this edition of the journal proffer an eloquent disquisition on alveolar compliance and resistance and describe ways in which we could make estimates of the effect of ventilation changes, using esophageal balloon manometry measure the trans alveolar pressure, and estimating the alveolar tidal volume using volumetric capnometry. 10 The article like the subject it addresses is complex and requires an active rather than passive read. It outlines the concepts clearly and highlights the need for accurate and exacting measurement. Complicating this is the need to provide simultaneous diaphragmatic and alveolar protective ventilation, which further complicates modelling of controlled ventilation strategies. 11 It remains something to be addressed in the future.

The optimal PEEP after alveolar recruitment maneuver assessed by electrical impedance tomography in healthy horses.

Electrical impedance tomography (EIT) has been an essential tool for assessing pulmonary ventilation in several situations, such as the alveolar recruitment maneuver (ARM) in PEEP titration to maintain the lungs open after atelectasis reversion. In the same way as in humans and dogs, in horses, this tool has been widely used to assess pulmonary aeration undergoing anesthesia, mechanical ventilation, recruitment maneuver, standing horses, or specific procedures. The present study aimed to evaluate the distribution of regional ventilation during ARM based on lung monitoring assessment by EIT, with a focus on better recruitment associated with less or no overdistention. Fourteen horses of 306 ± 21 kg undergoing isoflurane anesthesia in dorsal recumbency were used. The animals were mechanically ventilated with a tidal volume of 14 ml kg-1 and a respiratory rate of 7-9. An alveolar recruitment maneuver was instituted, increasing the PEEP by five cmH2O every 5 min until 32 cmH2O and decreasing it by five cmH2O every 5 min to 7 cmH2O. At each step of PEEP, arterial blood samples were collected for blood gas analysis, EIT images, hemodynamic, and respiratory mechanics. Associated with the CoV-DV increase, there was a significant decrease in the DSS during the ARM and a significant increase in the NSS when PEEP was applied above 12 cmH2O compared to baseline. The ComplROI showed a significant increase in the dependent area and a significant decrease in the non-dependent area during ARM, and both were compared to their baseline values. The driving pressure decreased significantly during the ARM, and Cst, PaO2, and PaO2/FiO2 ratio increased significantly. The VD/VT decreased significantly at DEPEEP17 and DEPEEP12. There was an HR increase at INPEEP27, INPEEP 32, and DEPEEP17 (p < 0.0001; p < 0.0001; and p < 0.05, respectively), those values being above the normal reference range for the species. The SAP, MAP, DAP, CI, and DO2I significantly decreased INPEEP32 (p < 0.05). The ARM by PEEP titration applied in the present study showed better ventilation distribution associated with better aeration in the dependent lung areas, with minimal overdistention between PEEP 17 and 12 cmH2O decreasing step. Those changes were also followed by improvements in static and regional compliance associated with increased oxygenation and pulmonary ventilation. ARM promoted a transitory decrease in arterial blood pressure and depression in CI with a concomitant drop in oxygen delivery, which should be best investigated before its routine use in clinical cases.

Impact of Two Resuscitation Sequences on Alveolar Ventilation during the First Minute of Simulated Pediatric Cardiac Arrest: Randomized Cross-Over Trial.

The International Liaison Committee on Resuscitation regularly publishes a Consensus on Science with Treatment Recommendations, but guidelines can nevertheless differ when knowledge gaps persist. In case of pediatric cardiac arrest, the American Heart Association recommends following the adult resuscitation sequence, i.e., starting with chest compressions. Conversely, the European Resuscitation Council advocates the delivery of five initial rescue breaths before starting chest compressions. This was a superiority, randomized cross-over trial designed to determine the impact of these two resuscitation sequences on alveolar ventilation in a pediatric model of cardiac arrest. The primary outcome was alveolar ventilation during the first minute of resuscitation maneuvers according to the guidelines used. A total of 56 resuscitation sequences were recorded (four sequences per team of two participants). The ERC approach enabled higher alveolar ventilation volumes (370 mL [203−472] versus 276 mL [140−360], p < 0.001) at the cost of lower chest compression fractions (57% [54;64] vs. 66% [59;68], p < 0.001). Although statistically significant, the differences found in this simulation study may not be clinically relevant. Therefore, and because of the importance of overcoming barriers to resuscitation, advocating a pediatric-specific resuscitation algorithm may not be an appropriate strategy.

First week of life respiratory management and pulmonary ventilation/perfusion matching in infants with bronchopulmonary dysplasia: a retrospective observational study

ObjectiveTo investigate the association between early neonatal respiratory management in infants with bronchopulmonary dysplasia (BPD) and the degree of pulmonary ventilation perfusion-matching (V/Q) at term.Methods30 preterm infants with a diagnosis of BPD who were initially treated with either controlled mechanical ventilation/continuous positive airway pressure (CMV/CPAP) (n = 14) or high-frequency oscillatory ventilation (HFOV) using a high lung-volume strategy (n = 16) were retrospectively included in this study. All infants underwent pulmonary V/Q single photon emission computed tomography at a median postmenstrual age of 37 weeks.ResultsInfants treated with HFOV had significantly larger proportion of the lung with matched V/Q as compared to infants treated with CMV/CPAP, median (interquartile range) 60.4% (55.5–66.0%) and 45.8% (37.8–53.1%) respectively (p = 0.01).ConclusionsIn infants who needed mechanical ventilation the first week of life and later developed BPD an association was observed between treatment with a HFOV and better pulmonary V/Q matching at near-term age.

Participation of the angiotensinergic and vasopressinergic mechanisms in the maintenance of cardiorespiratory parameters in sodium depleted rats

Changes in blood volume can be caused by different conditions, such as vomiting, diarrhea, alteration of sodium intake, trauma, or the use of diuretics, which can lead to severe health deterioration. Understanding the mechanisms involved in the maintenance of physiological parameters and the hydroelectrolytic balance of the human body during hypovolemia, can help with preventing and handling these high-risk situations. Hence, this study investigated cardiorespiratory [mean arterial pressure (MAP), heart rate (HR), pulmonary ventilation (VE)] and blood parameters, of sodium depleted rats with furosemide and the roles of the central and peripheral renin-angiotensin and the peripheral vasopressinergic systems in controlling blood pressure in these animals. Different groups under the same conditions received subcutaneous (s.c.) injections of furosemide (diuretic/saliuretic) or vehicle, intracerebroventricular (i.c.v.) or intravenous (i.v.) injections of losartan [angiotensin II (ANG II) AT1 receptor antagonist] or saline, and i.v. injections of Manning compound (AVPX, vasopressin V1 receptor antagonist). Sodium depletion increased the VE (708 ± 71, vs. normovolemic: 478 ± 40 mL/min/kg body wt) and did not modify baseline mean arterial pressure (104 ± 4, vs. normovolemic: 105 ± 4 mmHg) and heart rate (334 ± 20, vs. normovolemic: 379 ± 13 bpm). The i.v. losartan (10 mg/kg of body wt) treatment significantly reduced MAP in all groups and elevated HR, with a greater impact in sodium depleted rats before repletion. On the other hand, the i.c.v. losartan (3.3 μg/kg of body wt) and i.v. AVPX (10 μg/kg of body wt) treatments did not alter the MAP and HR in control, sodium depleted, and sodium repleted rats. These results indicate that sodium depletion affects cardiorespiratory control increasing baseline ventilation and peripheral angiotensinergic mechanisms are relevant for maintaining cardiovascular parameters in sodium depleted rats. Besides, this study suggests vasopressin V1 receptors do not participate in the maintenance of MAP and HR in sodium depleted animals with furosemide.

Perfusion imaging heterogeneity during NO inhalation distinguishes pulmonary arterial hypertension (PAH) from healthy subjects and has potential as an imaging biomarker

BackgroundWithout aggressive treatment, pulmonary arterial hypertension (PAH) has a 5-year mortality of approximately 40%. A patient’s response to vasodilators at diagnosis impacts the therapeutic options and prognosis. We hypothesized that analyzing perfusion images acquired before and during vasodilation could identify characteristic differences between PAH and control subjects.MethodsWe studied 5 controls and 4 subjects with PAH using HRCT and 13NN PET imaging of pulmonary perfusion and ventilation. The total spatial heterogeneity of perfusion (CV2Qtotal) and its components in the vertical (CV2Qvgrad) and cranio-caudal (CV2Qzgrad) directions, and the residual heterogeneity (CV2Qr), were assessed at baseline and while breathing oxygen and nitric oxide (O2 + iNO). The length scale spectrum of CV2Qr was determined from 10 to 110 mm, and the response of regional perfusion to O2 + iNO was calculated as the mean of absolute differences. Vertical gradients in perfusion (Qvgrad) were derived from perfusion images, and ventilation-perfusion distributions from images of 13NN washout kinetics.ResultsO2 + iNO significantly enhanced perfusion distribution differences between PAH and controls, allowing differentiation of PAH subjects from controls. During O2 + iNO, CV2Qvgrad was significantly higher in controls than in PAH (0.08 (0.055–0.10) vs. 6.7 × 10–3 (2 × 10–4–0.02), p < 0.001) with a considerable gap between groups. Qvgrad and CV2Qtotal showed smaller differences: − 7.3 vs. − 2.5, p = 0.002, and 0.12 vs. 0.06, p = 0.01. CV2Qvgrad had the largest effect size among the primary parameters during O2 + iNO. CV2Qr, and its length scale spectrum were similar in PAH and controls. Ventilation-perfusion distributions showed a trend towards a difference between PAH and controls at baseline, but it was not statistically significant.ConclusionsPerfusion imaging during O2 + iNO showed a significant difference in the heterogeneity associated with the vertical gradient in perfusion, distinguishing in this small cohort study PAH subjects from controls.

Automated didactic prototype of pulmonary ventilation exhibits a simulation of intrathoracic pressure variations during diaphragmatic function

The movement of air from the environment to the alveoli is a vital and complex phenomenon that occurs due to variations in intrathoracic and airway pressures in relation to the atmosphere. The construction of didactic prototypes can minimize the abstraction required in these in vivo phenomena. In this study, we automated a didactic prototype of pulmonary ventilation already described in literature to simulate and exhibit variations in intrathoracic pressure during diaphragmatic function. A pulmonary ventilation (PV) prototype was produced with recyclable materials, and automated by adapting a pressure sensor in the system to generate pressure curves as a function of time during the simulation of diaphragmatic function. The automated plunger’s downward traction induced by the servomotor (such as diaphragmatic) reduced the pressure inside the bottle (intrathoracic), and this variation can be observed graphically on a computer interface while the balloon was expanded, and atmospheric air invaded its interior. Conclusion: The incorporation of technology into a simple PV prototype allowed a safe and simulated demonstration of how the diaphragm induces the variation of the intrathoracic pressure in relation to the atmosphere concomitantly with the pulmonary deformation that occurs during inspiration and exhalation.

Knockdown of Brg1 reduced mucus secretion in HDM stimulated airway inflammation

BackgroundThe Brg1 (Brahma-related gene 1) is an important chromatin remodeling factor protein. The Brg1 protein can promote the transcriptional activation or inhibit target genes through regulating ATP hydrolysis which rearranges the nucleosomes position and the histone DNA interaction. In this study, we explored the role of Brg1 in house dust mite (HDM) stimulated airway inflammation. MethodsThe wild-type C57BL/6 mice (wild-type, WT) and alveolar epithelial cells specifically knockout Brg1 mice (Brg1fl/fl) were selected as the experimental subjects. HDM was used to stimulate human bronchial epithelial cells (16HBE) to construct an model of airway inflammation in vitro. The asthma group was established with HDM, and the control group was treated with normal saline. Wright's staining for the detection of differential counts of inflammatory cells in bronchoalveolar lavage fluid (BALF). Invasive lung function was used to assess the airway compliance. Hematoxylin and eosin (HE) staining and periodic acid-schiff (PAS) staining were used to detect mucus secretion. Immunohistochemistry was used to measure mucin glycoprotein 5AC (MUC5AC) protein expression in airway epithelium. Western blotting was used to detect the MUC5AC and JAK1/2-STAT6 proteins in mouse lung tissues and 16HBE cells. Co-immunoprecipitation (Co-IP) and Chromatin Immunoprecipitation (CHIP) were used to detect whether Brg1 could regulate the JAK1/2-STAT6 signaling pathway. ResultsThe airway inflammation, pulmonary ventilation resistance, airway mucus secretion, MUC5AC and IL-13 in BALF and MUC5AC protein expression in lung tissue of Brg1 knockout mice stimulated by HDM were lower than those of wild-type mice. The expression of MUC5AC protein in HDM stimulated Brg1 knockdown 16HBE cells was significantly lower than that in the control group. In vivo and in vitro, it was found that the activation of JAK1/2-STAT6 signal pathway in mouse lung tissue or 16HBE cells was inhibited after knockdown of Brg1 gene. The Co-IP and CHIP results showed that Brg1 could bind to the JAK1/2 promoter region and regulate the expression of JAK1/2 gene. ConclusionThe Brg1 may promote the secretion of airway mucus stimulated by HDM through regulating the JAK1/2-STAT6 pathway. Knockdown of Brg1 reduced mucus secretion in HDM stimulated airway inflammation.

Характеристика стійкого стану функцій спортсменів у видах спорту з варіативними умовами змагальної діяльності

The purpose of the study was to develop generalized and specific characteristics of the steady state of the highly qualified athletes, who specialize in the standard program of sports dance and boxing. Materials and methods. Twenty sportsmen-dancers and twenty boxers of high qualification took part in the research. Gas analysis. Measurements of О2 consumption reaction, СО2 emissions, minute volume of breathing were carried out using the MetaMax 3B analyzer. Ergometry. Modeling of standard conditions of measurement was carried out on the basis of bicycle ergometer Monark. Standard conditions are associated with the use of a given ergometric load power of 50 W. The composition of Cardiorespiratory Intermittent endurance test included eight accelerated 10-second intervals, eight 20-second rest intervals. The duration of the task is four minutes. Mathematic statistics. Descriptive statistics suggested determining the arithmetic mean – x ̅, standard deviation – S, as well as median – Me, maximum (max) and minimum (min) indices, 25% and 75% indices. Steady state is a period of competitive activity, in the process of which sportsmen demonstrate high level of technical and tactical skills and physical performance. Steady state diagnostics is an essential reserve for managing the functional support of special performance of athletes in sports with variable conditions of competitive activity. Results and discussion. An increase in the response of pulmonary ventilation indicates its role as a response to respiratory compensation of metabolic acidosis. Differences in the breathing response in standard measurement conditions are related to the specificity of the breathing response of athletes-dancers. To some extent, “artificial” management of the breathing response causes a decrease in the intensity of breathing cycles. Empirical knowledge indicates that this refers to the “aesthetic” component of the judges' assessment of the performance of the sports dance program. To some extent, this is related to the specifics of the formation of programs of special physical training, correction of certain structural components of functional maintenance of working capacity, in this case, the respiratory system. Another obvious fact is related to the structure of the load, when the intensity of the work of boxers causes more significant acidemic shifts and, as a result, predicts an increase in the reaction of pulmonary ventilation as a mechanism for removing excess CO2 during work. The increase (maintenance) of the O2 consumption response of athletes-dancers is associated with the formation of excess CO2 within the RER – 1.03–1.05 and excessive pulmonary ventilation in the range of 37.2–39.1. Boxers, respectively, with the formation of excess CO2 within the limits of RER – 1.07–1.09 and excessive pulmonary ventilation in the range of 40.0–44.1. The increase in excess ventilation in the third-fifth of dancers was 4.9%, 9.9% – in boxers, provided that the O2 consumption reaction remained stable. Conclusion. The steady state of the functional support of the special performance of athletes in sports with variable conditions of competitive activity ensures the stable development of cardio-respiratory system and aerobic energy supply in the middle of intense motor activity

Heart Rate Variability as an Indicator of the Regulatory Mechanism Condition in Body Physiological Adaptation

Research relevance: this article deals with aspects of heart rate variability (HRV) indicators as an indicator of the state of regulatory mechanisms of physiological adaptation of the body of foreign students in the process of education. Research purpose: analysis of HRV indicators, the state of the cardiovascular system (CVS), and the pulmonary ventilation system, as indicators of the state of the regulatory mechanisms of physiological adaptation of the body of foreign students in the process of education. Research materials and methods: students at the international school of medicine (ISM) were invited to the International University of Kyrgyzstan (IUK) (from the Republic of Pakistan) for 3 years of study. Anthropometric data (body mass index (BMI), pulse and arterial pressure indicators, vital capacity of the lungs (PE) (peak flowmetry), which are indicators of the physiological state of the body; particular changes in the spectral characteristics of the heart rhythm of foreign students during mental load (measurement VSR at rest and with load); the level of load endurance CVS. Research results: the main role in changes in regulatory mechanisms belongs to the cardiorespiratory system, which is responsible for supplying organs and tissues with oxygen and nutrients. Parameters of VSR allow assessing not only the existing state of health of a person, but also his potential opportunities. Conclusions: these research results are an important aspect for the development of concepts of regulation of psychological and physical stress during the development of the curriculum of medical faculties.

Modeling Physiological Predictors of Running Velocity for Endurance Athletes.

Background: Properly performed training is a matter of importance for endurance athletes (EA). It allows for achieving better results and safer participation. Recently, the development of machine learning methods has been observed in sports diagnostics. Velocity at anaerobic threshold (VAT), respiratory compensation point (VRCP), and maximal velocity (Vmax) are the variables closely corresponding to endurance performance. The primary aims of this study were to find the strongest predictors of VAT, VRCP, Vmax, to derive and internally validate prediction models for males (1) and females (2) under TRIPOD guidelines, and to assess their machine learning accuracy. Materials and Methods: A total of 4001 EA (nmales = 3300, nfemales = 671; age = 35.56 ± 8.12 years; BMI = 23.66 ± 2.58 kg·m-2; VO2max = 53.20 ± 7.17 mL·min-1·kg-1) underwent treadmill cardiopulmonary exercise testing (CPET) and bioimpedance body composition analysis. XGBoost was used to select running performance predictors. Multivariable linear regression was applied to build prediction models. Ten-fold cross-validation was incorporated for accuracy evaluation during internal validation. Results: Oxygen uptake, blood lactate, pulmonary ventilation, and somatic parameters (BMI, age, and body fat percentage) showed the highest impact on velocity. For VAT R2 = 0.57 (1) and 0.62 (2), derivation RMSE = 0.909 (1); 0.828 (2), validation RMSE = 0.913 (1); 0.838 (2), derivation MAE = 0.708 (1); 0.657 (2), and validation MAE = 0.710 (1); 0.665 (2). For VRCP R2 = 0.62 (1) and 0.67 (2), derivation RMSE = 1.066 (1) and 0.964 (2), validation RMSE = 1.070 (1) and 0.978 (2), derivation MAE = 0.832 (1) and 0.752 (2), validation MAE = 0.060 (1) and 0.763 (2). For Vmax R2 = 0.57 (1) and 0.65 (2), derivation RMSE = 1.202 (1) and 1.095 (2), validation RMSE = 1.205 (1) and 1.111 (2), derivation MAE = 0.943 (1) and 0.861 (2), and validation MAE = 0.944 (1) and 0.881 (2). Conclusions: The use of machine-learning methods allows for the precise determination of predictors of both submaximal and maximal running performance. Prediction models based on selected variables are characterized by high precision and high repeatability. The results can be used to personalize training and adjust the optimal therapeutic protocol in clinical settings, with a target population of EA.

Analysis of clinical features and genetic variants in three Chinese pedigrees affected with Limb girdle muscular dystrophy type 2I

To analyze the clinical features and genetic variants of three Chinese pedigrees affected with Limb girdle muscular dystrophy type 2I (LGMD2I). Clinical data and peripheral blood samples of the three probands and their family members were collected. Whole exome sequencing was carried out for the probands. Candidate variants were verified by Sanger sequencing of their family members. Probands 1 and 2 both featured weakness in the lower limbs. Proband 1 had lost walking ability and had pulmonary ventilation dysfunction. Proband 3 had lower limb pain, palpitations and asthma after exercise. Genetic sequencing revealed that proband 1 harbored compound heterozygous c.545A>G (p.Y182C) and c.1391A>T (p.N464I) variants of the FKRP gene, proband 2 harbored compound heterozygous c.545A>G (p.Y182C) and c.941C>T (p.T314M) variants of the FKRP gene, and proband 3 harbored compound heterozygous c.545A>G (p.Y182C) and c.161G>A (p.R54Q) variants. Among these, the c.161G>A (p.R54Q) variant was unreported previously. Compound heterozygous variants of the FKRP gene probably underlay the LGMD2I in the three patients. Whole exome sequencing is crucial for the diagnosis of LGMD2I. The identification of the novel variant also broadened the mutational spectrum of the FKRP gene.