Rebreathing Method Research Articles

Preconditioning with Moderate Hypoxia Increases Tolerance to Subsequent Severe Hypoxia in Rats with LPS-Induced Endotoxemia

Hyperproduction of mediators of LPS-induced inflammatory process (endotoxicosis, sepsis) initiates the development of acute respiratory failure (ARF), impaired gas exchange, progressive hypoxemia and hypercapnia, hypotension, respiratory arrest and death. Severe sepsis associated with hypoxemia remains the main cause of death, and therefore the development of methods to increase resistance to acute hypoxia in septic patients is an urgent task. The aim of the work was to study the effectiveness of preconditioning with short-term intermittent moderate hypoxia to increase tolerance to subsequent severe hypoxia in rats with LPS-induced endotoxicosis. The experiments were carried out on anesthetized and tracheostomated male Wistar rats. Endotoxicosis was modeled by administration of a lipopolysaccharide solution (Escherichia coli) in an amount of 7 mg/kg. To assess resistance to severe hypoxia, the rebreathing method of (RM) with a gradual decrease in oxygen in the rebreather from 21% to the onset of apnea was used. Hypoxic preconditioning (hypoxic training, HT) was also created by the method of RM in the mode of 3 cycles: reduction of the oxygen fraction in the rebreather to 12% – 3 min, 5 min – normoxia. 3 groups of animals were studied: I-control-NaCl, II–LPS, III–LPS+HT. The following parameters were recorded: external respiration, mean blood pressure (APm.), saturation (SpO2), fraction of inhaled O2, time of onset of apnea, the amount of spontaneous respiratory recovery (autoresuscitation) in the posthypoxic period. It was shown that the administration of LPS under normoxic conditions was accompanied by hyperventilation, hypoxemia and hypotension. The maximum deterioration in resistance to severe hypoxia was observed in rats with LPS, which was manifested by a decrease in APm, SpO2 and a decrease in the possibility of autoresuscitation after hypoxic apnea. The effect of HT prevented a decrease in blood pressure, SpO2 increased by 1.4 times, survival increased by 2 times, which is comparable to the level of normoxia before the introduction of LPS. It is assumed that the effectiveness of hypoxic preconditioning is due to the inhibition of the inflammatory response.

Nocturnal urination is associated with the presence of higher ventilatory chemosensitivity in patients with obstructive sleep apnea

PurposeChemosensitivity is an essential part of the pathophysiological mechanisms of obstructive sleep apnea (OSA). This study aims to use the rebreathing method to assess hypercapnic ventilatory response (HCVR) and analyze the association between chemosensitivity and certain symptoms in patients with OSA.MethodsA total of 104 male patients with diagnosed OSA were enrolled. The HCVR was assessed using rebreathing methods under hypoxia exposure to reflect the overall chemosensitivity. Univariate and multivariate linear regression were used to explore the association with chemosensitivity. Participants were enrolled in the cluster analysis using certain symptoms, basic characteristics, and polysomnographic indices.ResultsAt similar baseline values, the high chemosensitivity group (n = 39) demonstrated more severe levels of OSA and nocturnal hypoxia than the low chemosensitivity group (n = 65). After screening the possible associated factors, nocturnal urination, rather than OSA severity, was found to be positively associated with the level of chemosensitivity. Cluster analysis revealed three distinct groups: Cluster 1 (n = 32, 34.0%) held younger, obese individuals with nocturnal urination, elevated chemosensitivity level, and very severe OSA; Cluster 2 (41, 43.6%) included middle-aged overweighted patients with nocturnal urination, increased chemosensitivity level, but moderate-severe OSA; and Cluster 3 (n = 21, 22.3%) contained middle-aged overweighted patients without nocturnal urination, with a lowered chemosensitivity level and only moderate OSA.ConclusionThe presence of nocturnal urination in male patients with OSA may be a sign of higher levels of ventilatory chemosensitivity, requiring early therapy efforts independent of AHI levels.

Changes in hypoxic and hypercapnic ventilatory responses at high altitude measured using rebreathing methods.

Ventilatory responses to hypoxia and hypercapnia play a vital role in maintaining gas exchange homeostasis and in adaptation to high-altitude environments. This study investigates the mechanisms underlying sensitization of hypoxic and hypercapnic ventilatory response (HVR and HCVR, respectively) in individuals acclimatized to moderate high altitude (3,800 m). Thirty-one participants underwent chemoreflex testing using the Duffin-modified rebreathing technique. Measures were taken at sea level and after 2 days of acclimatization to high altitude. Ventilatory recruitment threshold (VRT), HCVR-Hyperoxia, HCVR-Hypoxia, and HVR were quantified. Acclimatization to high altitude resulted in increased HVR (P < 0.001) and HCVR-Hyperoxia (P < 0.001), as expected. We also observed that the decrease in VRT under hypoxic test conditions significantly contributed to the elevated HVR at high altitude since the change in VRT across hyperoxic and hypoxic test conditions was greater at high altitudes compared to baseline sea-level tests (P = 0.043). Pre-VRT, or basal, ventilation also increased at high altitudes (P < 0.001), but the change did not differ between oxygen conditions. Taken together, these data suggest that the increase in HVR at high altitude is at least partially driven by a larger decrease in the VRT in hypoxia versus hyperoxia at high altitude compared to sea level. This study highlights the intricacies of respiratory adaptations during acclimatization to moderate high altitude, shedding light on the roles of the VRT, baseline respiratory drive, and two-slope HCVR in this process. These findings contribute to our understanding of how human respiratory control responds to hypoxic and hypercapnic challenges at high altitude.NEW & NOTEWORTHY We report the first measurements of the hypoxic ventilatory response (HVR) after 2 days at high altitude using a CO2 rebreathing technique. We evaluated mechanisms by which the HVR becomes elevated with acclimatization (increased hypercapnic ventilatory response sensitivity in hypoxia, increased baseline respiratory drive in hypoxia, or lower ventilatory recruitment thresholds in hypoxia). For the first time, we report that decreases in the ventilatory recruitment threshold in hypoxia contribute to elevated HVR at high altitude.

Effect of Fluid Intake on Acute Changes in Plasma Volume: A Randomized Controlled Crossover Pilot Trial.

Plasma volume (PV) undergoes constant and dynamic changes, leading to a large intra-day variability in healthy individuals. Hydration is known to induce PV changes; however, the response to the intake of osmotically different fluids is still not fully understood. In a randomized controlled crossover trial, 18 healthy individuals (10 females) orally received an individual amount of an isotonic sodium-chloride (ISO), Ringer (RIN), or glucose (GLU) solution. Hemoglobin mass (Hbmass) was determined with the optimized carbon monoxide re-breathing method. Fluid-induced changes in PV were subsequently calculated based on capillary hemoglobin concentration ([Hb]) and hematocrit (Hct) before and then every 10 minutes until 120 min (t0-120) after the fluid intake and compared to a control trial arm (CON), where no fluid was administered. Within GLU and CON trial arms, no statistically significant differences from baseline until t120 were found (p > 0.05). In the ISO trial arm, PV was significantly increased at t70 (+138 mL, p = 0.01), t80 (+191 mL, p < 0.01), and t110 (+182 mL, p = 0.01) when compared to t0. Moreover, PV in the ISO trial arm was significantly higher at t70 (p = 0.02), t110 (p = 0.04), and t120 (p = 0.01) when compared to the same time points in the CON trial arm. Within the RIN trial arm, PV was significantly higher between t70 and t90 (+183 mL, p = 0.01) and between t110 (+194 mL, p = 0.03) and t120 (+186 mL, p < 0.01) when compared to t0. These results demonstrated that fluids with a higher content of osmotically active particles lead to acute hemodilution, which is associated with a decrease in [Hb] and Hct. These findings underpin the importance of the hydration state on PV and especially on PV constituent levels in healthy individuals.

Effects of the Birthplace Altitude and Training Volume on Hematological Characteristics in Youth and Junior Male Colombian Cyclists.

The long-term development of talent in endurance sports is a topic of interest. Among various factors, the importance of total hemoglobin mass (tHbmass) and the potential benefits of being an altitude-native athlete remain unclear, particularly in young categories. This study aimed to investigate the impact of altitude and training content on hematological characteristics by comparing young male cyclists age 15-16 and 17-18years who were born and trained at a moderate altitude (ie,greater than or equal to 2500m; MA) and cyclists who were born and trained at low altitude (below 1000m; LA). tHbmass (in grams and grams per kilogram), measured by using the optimized carbon monoxide rebreathing method during an incremental test on a cycle ergometer; hematocrit percentage, hemoglobin concentration; and erythrocyte, blood, and plasma volume were measured in youth male cyclists age 15-16years and junior cyclists age 17-18years who were born and trained at MA versus LA. All variables were analyzed with a 2-way (age [youth cyclist vs junior cyclist] × altitude level [MA vs LA]) analysis of variance with subsequent Tuckey post hoc test. Some altitude-induced benefits were reported in cyclists at age 15-16years in the MA group with higher values in hematocrit percentage, hemoglobin concentration, and tHbmass (grams per kilogram) (P < .05) than their LA counterparts. This was also observed at age 17-18years (P < .001), except for tHbmass, wherein no significant difference was found between MA and LA groups. In contrast, plasma volume was lower in MA than LA junior cyclists. (1) The altitude of birth and residence could generate an advantage in tHbmass in young male cyclists age 15-16 and 17-18years who train at MA compared with cyclists who are born and train at LA. (2) Altitude-induced benefits in physiological variables (hematocrit percentage, hemoglobin concentration, tHbmass in g·kg-1) were reported in cyclists at age 15-16years and partially at age 17-18years. In contrast, plasma volume was lower in MA than in LA junior cyclists. This may impact the strategies for identifying and developing talent in cycling.

Non-Invasive Cardiac Output Measurement Using Inert Gas Rebreathing Method during Cardiopulmonary Exercise Testing-A Systematic Review.

The use of inert gas rebreathing for the non-invasive cardiac output measurement has produced measurements comparable to those obtained by various other methods. However, there are no guidelines for the inert gas rebreathing method during a cardiopulmonary exercise test (CPET). In addition, there is also a lack of specific standards for assessing the non-invasive measurement of cardiac output during CPET, both for healthy patients and those suffering from diseases and conditions. This systematic review aims to describe the use of IGR for a non-invasive assessment of cardiac output during cardiopulmonary exercise testing and, based on the information extracted, to identify a proposed CPET report that includes an assessment of the cardiac output using the IGR method. This systematic review was conducted by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) guidelines. PubMed, Web of Science, Scopus, and Cochrane Library databases were searched from inception until 29 December 2022. The primary search returned 261 articles, of which 47 studies met the inclusion criteria for this review. This systematic review provides a comprehensive description of protocols, indications, technical details, and proposed reporting standards for a non-invasive cardiac output assessment using IGR during CPET. It highlights the need for standardized approaches to CPET and identifies gaps in the literature. The review critically analyzes the strengths and limitations of the studies included and offers recommendations for future research by proposing a combined report from CPET-IGR along with its clinical application.

Intravascular volumes and the influence on anemia assessed by a carbon monoxide rebreathing method in patients undergoing maintenance hemodialysis.

Fluid overload is a major challenge in hemodialysis patients and might cause hypervolemia. We speculated that hemodialysis patients reaching dry weight could have undetected hypervolemia and low hemoglobin (Hb) concentration (g/dL) due to hemodilution. The study included hemodialysis patients (n = 22) and matched healthy controls (n = 22). Blood volume, plasma volume, red blood cell volume, and total Hb mass were determined using a carbon monoxide (CO)-rebreathing method in hemodialysis patients reaching dry weight and controls. Blood volume measurements were also obtained by a dual-isotope labeling technique in a subgroup for validation purposes. In the hemodialysis group, the median specific blood volume was 89.3 mL/kg (interquartile range [IQR]: 76.7-95.4 mL/kg) and was higher than in the control group (79.9 mL/kg [IQR: 70.4-88.0 mL/kg]; p < 0.037). The median specific plasma volume was 54.7 mL/kg (IQR: 47.1-61.0 mL/kg) and 44.0 mL/kg (IQR: 38.7-49.5 mL/kg) in the hemodialysis and control groups, respectively (p < 0.001). Hb concentration was lower in hemodialysis patients (p < 0.001), whereas no difference in total Hb mass was observed between groups (p = 0.11). A correlation was found between blood volume measured by the CO-rebreathing test and the dual-isotope labeling technique in the control group (r = 0.83, p = 0.015), but not the hemodialysis group (r = 0.25, p = 0.60). The hemodialysis group had increased specific blood volume at dry weight due to high plasma volume, suggesting a hypervolemic state. However, correlation was not established against the dual-isotope labeling technique underlining that the precision of the CO-rebreathing test should be further validated. The total Hb mass was similar between hemodialysis patients and controls, unlike Hb concentration, which emphasizes that Hb concentration is an inaccurate marker of anemia among hemodialysis patients.

Cardiovascular responses of exercises performed within the extreme exercise domain.

Stroke volume (SV), heart rate (HR) and arterio-venous O2 difference (a-vO2diff) responses to heavy and severe-intensity exercise have been well documented; however, there is a lack of information on the SV, HR and a v-O2diff responses of work rates within extreme exercise domain. The aim of this study was, therefore, to focus on central and peripheral components of VO2 responses to exercises performed within the heavy, severe and extreme exercise domain. Eight well-trained male cyclists participated in this study. Maximal O2 consumption (VO2max) and corresponding work rate (P@VO2max) were determined by multisession constant work rate exercises. Cardiovascular responses to exercises were evaluated by nitrous-oxide rebreathing method with work rates from 40 % to 160 % of P@VO2max, VO2max corresponded to 324+/-39.4 W; however, maximal SV responses occurred at 205+/-54.3 W (p<0.01). Maximal cardiac output (Q), HR, and a vO2diff responses were revealed by the P@VO2max. VO2 response to exercise significantly decreased from severe-intense exercises to the first work rate of extreme exercise domain due to significant decreases in Q, SV, and HR responses (p<0.05), except a v-O2diff (p>0.05). Moreover, non-significant decreases in Q, SV, and a v-O2diff were evaluated as response to increase in work rate belonging to extreme work rates (p>0.05), except the HR (p<0.05). Work rates within the lower district of the extreme exercise domain have an important potential to improve peripheral component of VO2, while the P@VO2max seems the most appropriate intensity for aerobic endurance development as it maximizes the central component of VO2max.

#2694 URAEMIC CARDIOMYOPATHY AS PREMATURE PRESBYCARDIA

Abstract Background and Aims Presbycardia, the age-related decline in cardiac function, has been shown in the general population by demonstrating gradual decline in peak cardiac performance with advancing age [1]. Chronic kidney disease (CKD) has shown phenotypic similarities with premature aging. Studies have shown accelerated vascular aging and skeletal muscle wasting in CKD. However, it is not known whether CKD patients show age related decline in cardiac function and whether the impairment is more pronounced for the given age (premature presbycardia). In the present study, we set out to test the hypothesis that CKD patients have premature presbycardia by measuring peak cardiac power (CPOpeak) non-invasively across different age groups. Method A cross sectional study (n = 170) of healthy male volunteers (n = 100) and male CKD patients (n = 70) spanning ages 19 to 75 years. CKD patients were grouped into early (CKD 2–3, n = 29) and late CKD (CKD 4–5, n = 41). Patients with diabetes or any known cardiovascular diseases were excluded. CPOpeak was measured using a specialised cardiopulmonary exercise test (CPX) using CO2 rebreathing method [2]. The association between age and CPOpeak was evaluated. The regression lines of CKD patients and healthy volunteers were compared using ANCOVA. P&amp;lt;0.05 is considered significant. Results The mean eGFR of early CKD and late CKD were 57.8±17.2 ml/min and 16.8±5.8 ml/min respectively. The mean CPOpeak of the study groups were 5.35±0.94 W (Control), 4.93±0.71 W (early CKD) and 4.26±0.69 W (late CKD). Fig. 1 shows the association between CPOpeak and age along with the regression equations for the individual study groups. Comparison of the regression lines using ANCOVA did not show any difference in slopes between the groups (P = NS). There was a diminution in CPOpeak of 0.2W per 10 years of advancing age. However, for any given age, the CPOpeak was diminished by 0.38 W in early CKD (P = 0.023) and 0.93 W in late CKD (P&amp;lt;10−3) compared to control. In other words, the cardiac age was older by 19 years in early CKD and by 46.5 years in late CKD compared to healthy volunteers. Conclusion The results demonstrate that CKD is associated with premature presbycardia. This phenomenon may offer explanation for the high prevalence of heart failure in advanced CKD. Further studies exploring the underlying mechanisms of premature aging in CKD may be worthwhile in the future.

Hemoglobin mass and performance responses during 4 weeks of normobaric "live high-train low and high".

To investigate whether 4 weeks of normobaric "live high-train low and high" (LHTLH) causes different hematological, cardiorespiratory, and sea-level performance changes compared to living and training in normoxia during a preparation season. Nineteen (13 women, 6 men) cross-country skiers competing at the national or international level completed a 28-day period (∼18 h day-1 ) of LHTLH in normobaric hypoxia of ∼2400 m (LHTLH group) including two 1 h low-intensity training sessions per week in normobaric hypoxia of 2500 m while continuing their normal training program in normoxia. Hemoglobin mass (Hbmass ) was assessed using a carbon monoxide rebreathing method. Time to exhaustion (TTE) and maximal oxygen uptake (VO2max ) were measured using an incremental treadmill test. Measurements were completed at baseline and within 3 days after LHTLH. The control group skiers (CON) (seven women, eight men) performed the same tests while living and training in normoxia with ∼4 weeks between the tests. Hbmass in LHTLH increased 4.2 ± 1.7% from 772 ± 213 g (11.7 ± 1.4 g kg-1 ) to 805 ± 226 g (12.5 ± 1.6 g kg-1 ) (p < 0.001) while it was unchanged in CON (p = 0.21). TTE improved during the study regardless of the group (3.3 ± 3.4% in LHTLH; 4.3 ± 4.8% in CON, p < 0.001). VO2max did not increase in LHTLH (61.2 ± 8.7 mL kg-1 min-1 vs. 62.1 ± 7.6 mL kg-1 min-1 , p = 0.36) while a significant increase was detected in CON (61.3 ± 8.0-64.0 ± 8.1 mL kg-1 min-1 , p < 0.001). Four-week normobaric LHTLH was beneficial for increasing Hbmass but did not support the short-term development of maximal endurance performance and VO2max when compared to the athletes who lived and trained in normoxia.

Cardiopulmonary exercise testing and heart failure: a tale born from oxygen uptake.

Since 50 years, cardiopulmonary exercise testing (CPET) plays a central role in heart failure (HF) assessment. Oxygen uptake (VO2) is one of the main HF prognostic indicators, then paralleled by ventilation to carbon dioxide (VE/VCO2) relationship slope. Also anaerobic threshold retains a strong prognostic power in severe HF, especially if expressed as a percent of maximal VO2 predicted value. Moving beyond its absolute value, a modern approach is to consider the percentage of predicted value for peak VO2 and VE/VCO2 slope, thus allowing a better comparison between genders, ages, and races. Several VO2 equations have been adopted to predict peak VO2, built considering different populations. A step forward was made possible by the introduction of reliable non-invasive methods able to calculate cardiac output during exercise: the inert gas rebreathing method and the thoracic electrical bioimpedance. These techniques made possible to calculate the artero-venous oxygen content differences (ΔC(a-v)O2), a value related to haemoglobin concentration, pO2, muscle perfusion, and oxygen extraction. The role of haemoglobin, frequently neglected, is however essential being anaemia a frequent HF comorbidity. Finally, peak VO2 is traditionally obtained in a laboratory setting while performing a standardized physical effort. Recently, different wearable ergo-spirometers have been developed to allow an accurate metabolic data collection during different activities that better reproduce HF patients' everyday life. The evaluation of exercise performance is now part of the holistic approach to the HF syndrome, with the inclusion of CPET data into multiparametric prognostic scores, such as the MECKI score.

Influence of rapidly oscillating inspired O2 and N2 concentrations on pulmonary vascular function and lung fluid balance in healthy adults.

Introduction: Aircrew may experience rapidly oscillating inspired O2/N2 ratios owing to fluctuations in the on-board oxygen delivery systems (OBOG). Recent investigations suggest these oscillations may contribute to the constellation of physiologic events in aircrew of high-performance aircraft. Therefore, the purpose of this study was to determine whether these "operationally-relevant" environmental challenges may cause decrements in measures of pulmonary vascular physiology. Methods: Thirty healthy participants (Age: 29 ± 5years) were recruited and assigned to one of the three exposures. Participants were instrumented for physiologic monitoring and underwent baseline cardiopulmonary physiology testing (ground level) consisting of a rebreathe method for quantifying pulmonary blood flow (Qc), pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (Dm). Ultrasound was used to quantify "comet tails" (measure of lung fluid balance). After baseline testing, the participants had two 45min exposures to an altitude of 8,000ft where they breathed from gas mixtures alternating between 80/20 and 30/70 O2/N2 ratios at the required frequency (30s, 60s, or 120s), separated by repeat baseline measure. Immediately and 45min after the second exposure, baseline measures were repeated. Results: We observed no changes in Qc, Dm or Vc during the 60s exposures. In response to the 30s oscillation exposure, there was a significantly reduced Qc and Vc at the post-testing period (p = 0.03). Additionally, exposure to the 120s oscillations resulted in a significant decrease in Vc at the recovery testing period and an increase in the Dm/Vc ratio at both the post and recovery period (p < 0.01). Additionally, we observed no changes in the number of comet tails. Conclusion: These data suggest "operationally-relevant" changes in inspired gas concentrations may cause an acute, albeit mild pulmonary vascular derecruitment, reduced distention and/or mild pulmonary-capillary vasoconstriction, without significant changes in lung fluid balance or respiratory gas exchange. The operational relevance remains less clear, particularly in the setting of additional environmental stressors common during flight (e.g., g forces).

Validity and reliability of capillary vs. Venous blood for the assessment of haemoglobin mass and intravascular volumes.

Objectives: Haemoglobin mass (Hbmass) assessment with the carbon monoxide rebreathing method is a more accurate estimate than other measures of oxygen-carrying capacity. Blood may be collected by several means and differences in the measured variables may exist as a result. The present study assessed the validity and reliability of calculated Hbmass and intravascular volumes obtained from capillary blood (CAP) when compared to venous blood (VEN) draws. Methods: Twenty-two adults performed a carbon monoxide rebreathing procedure with paired VEN and CAP draws at baseline, pre-rebreathing and post-rebreathing (POST). Thirteen of these participants performed this protocol on two occasions to assess the data reliability from both blood sampling sites. In a second experiment, 14 adults performed a 20-min seated and a 20-min supine rest to assess for the effect of posture on haematological parameters. Results: Haemoglobin mass (CAP = 948.8 ± 156.8g; VEN = 943.4 ± 157.3 g, p = 0.108) and intravascular volume (CAP = 6.5 ± 1L; VEN = 6.5 ± 0.9 L, p = 0.752) were statistically indifferent, had low bias (Hbmass bias = 14.45 ± 40.42g, LoA -64.78g-93.67g) and were highly correlated between sampling techniques. Reliability analysis demonstrated no difference in the mean change in variables calculated from both sampling sites and good to excellent intraclass correlation coefficients (>0.700), however, typical measurement error was larger in variables measured using CAP (VEN Hbmass TE% = 2.1%, CAP Hbmass TE% = 5.5%). The results indicate that a supine rest prior to the rebreathing protocol would have a significant effect on haemoglobin concentration and haematocrit values compared to a seated rest, with no effect on carboxyhaemoglobin %. Conclusion: The present study demonstrates that CAP and VEN were comparable for the calculation of Hbmass and intravascular volumes in terms of accuracy. However, reduced reliability and increased error in the CAP variables indicates that there are methodological considerations to address when deciding which blood drawing technique to utilise. To reduce this CAP error, increased replicate analyses are required.

Strategies to improve respiratory chemoreflex characterization by Duffin's rebreathing.

What is the central question of this study? We assessed the test-retest variability of respiratory chemoreflex characterization by Duffin's modified rebreathing method and explored whether signal averaging of repeated trials improves confidence in parameter estimation. What is the main finding and its importance? Modified rebreathing is a reproducible method to characterize responses of central and peripheral respiratory chemoreflexes. Signal averaging of multiple repeated tests minimizes within- and between-test variability, improves the confidence of chemoreflex characterization and reduces the minimal change in parameters required to establish an effect. Future experiments that apply this method might benefit from signal averaging to improve its discriminatory effect. We assessed the test-retest variability of central and peripheral respiratory chemoreflex characterization by Duffin's modified rebreathing method and explored whether signal averaging of repeated trials improves confidence in parameter estimation. Over four laboratory visits, 13 participants (mean±SD age, 25±5years) performed six repetitions of modified rebreathing in isoxic-hypoxic conditions [end-tidal ( ) = 50mmHg] and isoxic-hyperoxic conditions ( =150mmHg). End-tidal ( ), and minute ventilation ( E ) were measured breath-by-breath, by gas analyser and pneumotachograph. The E versus relationships were fitted with a piecewise model to estimate the ventilatory recruitment threshold (VRT) and the slope above the VRT ( E S). Breath-by-breath data from the three within- and between-day trials were averaged using two approaches [simple average (fit then average) and ensemble average (average then fit)] and compared with a single-trial fit. Variability was assessed by intraclass correlation (ICC) and coefficient of variance (CV), and the minimal detectable change was computed for each approach using two independent sets of three trials. Within days, the VRT and E S exhibited excellent test-retest variability in both hyperoxic conditions (VRT: ICC=0.965, CV=2.3%; E S: ICC=0.932, CV=15.5%) and hypoxic conditions (VRT: ICC=0.970, CV=2.9%; E S: ICC=0.891, CV=17.2%). Between-day reproducibility was also excellent (hyperoxia, VRT: ICC=0.930, CV=2.2%; E S: ICC=0.918, CV=14.2%; and hypoxia, VRT: ICC=0.940, CV=3.0%; E S: ICC=0.880, CV=18.1%). Compared with a single-trial fit, there were no differences in VRT or E S using the simple average or ensemble average approaches; however, ensemble averaging reduced the minimal detectable change for E S from 2.95 to 1.39Lmin-1 mmHg-1 (hyperoxia) and from 3.64 to 1.82 Lmin-1 mmHg-1 (hypoxia). Single trials of modified rebreathing are reproducible; however, signal averaging of repeated trials improves confidence in parameter estimation.

Comparison of the automatised and the optimised carbon monoxide rebreathing methods

Recently, a new automated carbon monoxide (CO) rebreathing method (aCO) to estimate haemoglobin mass (Hbmass) was introduced. The aCO method uses the same CO dilution principle as the widely used optimised CO rebreathing method (oCO). The two methods differ in terms of CO administration, body position, and rebreathing time. Whereas with aCO, CO is administered automatically by the system in a supine position of the subject, with oCO, CO is administered manually by an experienced operator with the subject sitting. Therefore, the aim of this study was to quantify possible differences in Hbmass estimated with the two methods. Hbmass was estimated in 18 subjects (9 females, 9 males) with oCO using capillary blood samples (oCOc) and aCO taking simultaneously venous blood samples (aCOv) and capillary blood samples (aCOc). Overall, Hbmass was different between the three measurement procedures (F = 57.55, p < .001). Hbmass was lower (p < .001) for oCOc (737 g ± 179 g) than for both aCOv (825 g ± 189 g, −9.3%) and aCOc (835 g ± 189 g, −10.6%). There was no difference in Hbmass estimated with aCOv and aCOc procedures (p = .12). Three factors can likely explain the 10% difference in Hbmass: differences in calculations (including a factor for myoglobin flux), body position (distribution of CO in blood circulation) during rebreathing, and time of blood sampling. Moreover, the determination of Hbmass with aCO is possible with capillary blood sampling instead of venous blood sampling.

Thermal Rebreathing Model for Evaluation of Infant Bedding Materials

Abstract Carbon dioxide (CO2) rebreathing is a recognized hazard, particularly for infants. A new thermal rebreathing method and apparatus have been developed for measuring and comparing the degree to which various soft bedding materials perform with respect to this hazard. The new methodology simplifies the evaluation process and uses less costly equipment than the incumbent expensive and complex CO2 rebreathing model. Using warm air as a proxy for CO2, it relies on a highly sensitive differential thermometer to measure air temperature differences that correlate to the level of rebreathing. The apparatus is portable and requires neither the use of a gas analyzer nor a source of CO2. Test results comparing the two methods show strong correlation validating the new thermal concept. The availability of a simple CO2 rebreathing method and apparatus will promote quantitative evaluation of this hazard among a wider group of users, including infant product developers and manufacturers. Additional studies are suggested to further develop the thermal rebreathing model.

Removal of the influence of plasma volume fluctuations for the athlete biological passport and stability of haematological variables in active women taking oral contraception.

The haematological module of the athlete biological passport (ABP) monitors longitudinal haematological variations that could be indicative of blood manipulation. This study applied a multi‐parametric model previously validated in elite cyclists to compare inferred and actual PV variations, whereas the potential influence of the oral contraceptive pill (OCP) cycle on the ABP blood biomarkers and plasma volume (PV) in 14 physically active women taking OCPs was also investigated. Blood and serum samples were collected each week for 8 weeks, and the ABP haematological variables were determined according to the World Anti‐Doping Agency guidelines. Transferrin (sTFN), ferritin (FERR), albumin (ALB), calcium (Ca), creatinine (CRE), total protein (TP) and low‐density lipoprotein (LDL) were additionally computed as ‘volume‐sensitive’ variables in a multivariate analysis to determine individual estimations of PV variations. Actual PV variations were indirectly measured using a validated carbon monoxide rebreathing method. We hypothesised ABP markers to be stable during a standard OCP cycle and estimated PV variations similar to measured PV variations. Measured PV variations were in good agreement with the predictions and allowed to explain an atypical passport finding (ATPF). The ABP biomarkers, Hbmass and PV were stable over 8 weeks. Significant differences occurred only between Week 7 and Week 1, with lower levels of haemoglobin concentration ([Hb]), haematocrit (HCT) and red blood cell count (RBC)(−4.4%, p < 0.01; −5.1%, p < 0.01; −5.2%, p < 0.01) and higher levels of PV at week 7 (+9%, p = 0.05). We thus concluded that estimating PV variations may help interpret individual ABP haematological profiles in women.

Estimated plasma volume status is a modest predictor of true plasma volume excess in compensated chronic heart failure patients

Plasma volume and especially plasma volume excess is a relevant predictor for the clinical outcome of heart failure patients. In recent years, estimated plasma volume based on anthropometric characteristics and blood parameters has been used whilst direct measurement of plasma volume has not entered clinical routine. It is unclear whether the estimation of plasma volume can predict a true plasma volume excess. Plasma volume was measured in 47 heart failure patients (CHF, 10 female) using an abbreviated carbon monoxide rebreathing method. Plasma volume and plasma volume status were also estimated based on two prediction formulas (Hakim, Kaplan). The predictive properties of the estimated plasma volume status to detect true plasma volume excess > 10% were analysed based on logistic regression and receiver operator characteristics. The area under the curve (AUC) to detect plasma volume excess based on calculation of plasma volume by the Hakim formula is 0.65 (with a positive predictive value (PPV) of 0.62 at a threshold of − 16.5%) whilst the AUC for the Kaplan formula is 0.72 (PPV = 0.67 at a threshold of − 6.3%). Only the estimated plasma volume status based on prediction of plasma volume by the Kaplan formula formally appears as an acceptable predictor of true plasma volume excess, whereas calculation based on the Hakim formula does not sufficiently predict a true plasma volume excess. The low positive predictive values for both methods suggest that plasma volume status estimation based on these formulas is not suitable for clinical decision making.

VALIDITY OF THE STRINGER FORMULA FOR EVALUATING THE PROGRESSION OF CARDIAC STROKE VOLUME DURING INCREMENTAL EXERCISE

PURPOSE: The Stringer formula (ST; Stringer et al. 1997) aims to estimate cardiac output (Q̇) non-invasively during cardiopulmonary exercise testing (CPET). ST considers the arterio-venous oxygen difference as a function of the percentage oxygen consumption (V˙O2), where Q̇ST = V˙O2 / [5.72 + 0.105 * %V˙O2max]. If heart rate (HR) is known, stroke volume (SV) = Q̇/HR. It is unclear whether the progression of SV during incremental exercise (i.e., increase, plateau, or decrease) can be validly monitored via Q̇ST. Our aim was to compare the progression of SV obtained with ST with an established inert gas rebreathing method (RB). METHODS: Sixteen male participants (181 ± 8 cm, 78.0 ± 6.7 kg, 26 ± 4 years; V˙O2max 55 ± 10 mL/min/kg) completed an incremental test (6 steps, 3 min) ranging 40-90% V˙O2max with CPET and RB (Innocor, Innovision, DK) on a cycle ergometer. At the end of each stage, Q̇RB was measured via RB. V˙O2max had been determined before. The data set was analyzed graphically and statistically (regression, Bland-Altman plots, correlation). To assess individual progressions, SVST and SVRB were normalized (nor) to the corresponding maximum. Positive correlations of SVnorRB and SVnorST were used as indicators of progression agreement and also validated graphically. RESULTS: Ninety measurements >40% V˙O2max resulted in the following regressions: Q̇RB = 5.162*V˙O2 + 4.414 (r = 0.84) and Q̇ST = 4.658* V˙O2 + 8.511 (r = 0.91). The correlation of absolute Q̇ST vs. Q̇RB was r = 0.83 and SVST vs. SVRB was r = 0.71, respectively. Correlation of Q̇norST vs. Q̇norRB was r = 0.93 and SVnorST vs. SVnorRB was r = 0.21. The mean of the differences for Q̇RB-Q̇ST was -2.6 ± 2.9 L/min and for SVRB-SVST -20 ± 19 mL. In 12 participants, correlations between SVRB and SVST were positive (r ≥ 0.48 ≤ 0.86), indicating an agreement of the progression of SVST and SVRB. Four correlation coefficients were negative. Graphical analysis confirmed the interpretation of the correlation coefficients. CONCLUSIONS: Despite the strong correlation of Q̇RB vs. Q̇ST during incremental exercise, the progression of SVRB was not validly determined by ST in 25% of the participants. Hence, ST does not appear to be appropriate for this purpose.

A Comparative Assessment of Effects of Major Mediators ofAcute Phase Response (IL-1, TNF-α, IL-6) on Breathing Pattern and Survival Rate in Rats with Acute Progressive Hypoxia.

A pressing issue of the day is the identification of therapeutic targets to suppress the “cytokine storm” in COVID-19 complicated by acute respiratory distress syndrome (ARDS) with concomitant hypoxemia. However, the key cytokine and its relative contribution to the pathogenesis of ARDS, which leads to high mortality, are unknown. A comparative assessment of the effect of elevated systemic levels of pro-inflammatory cytokines IL-1β, TNF-1α and IL-6 on the respiratory patterns and survival rate in rats was carried out under progressively increasing acute hypoxia. Increasing hypoxia was simulated by a rebreathing method (from normoxia to apnea). The recorded parameters were the breathing pattern components (tidal volume and respiratory rate), minute ventilation (MV), oxygen saturation, apnea onset time, and posthypoxic survival rate. A comparative analysis was carried out under mild, moderate and severe hypoxia (at FIO2 = 15, 12 and 8%, respectively). It was shown that increasing hypoxia was accompanied by an acute suppression of the compensatory elevation of MV in rats with increased systemic levels of IL-1β and TNF-1α. By contrast, IL-6 caused an intensive elevation of MV with increasing hypoxia. Acute hypoxia (FIO2 < 8%), in all experimental series, was accompanied by an impairment of the respiratory rhythm up to the development of apnea. Posthypoxic breathing restoration (survival rate) was 50% with IL-1β and TNF-1α and only 10% with IL-6. The obtained results indicate that the elevated IL-6 level, despite the absence of respiratory disorders at the initial stage of the developing pathologic process, leads to a higher mortality in rats compared to IL-1β and TNF-1α. This allows considering IL-6 as an early prognostic biomarker of a high risk of mortality under severe hypoxemia.