Arterial O2 Saturation Research Articles

Fontan hemodynamics in adults with obesity compared to overweight and normal body mass index: a retrospective invasive exercise study.

The effects of obesity on Fontan hemodynamics are poorly understood. Accordingly, we assessed its impact on exercise invasive hemodynamics and exercise capacity. Seventy-seven adults post-Fontan undergoing exercise cardiac catheterization (supine cycle protocol) were retrospectively identified using an institutional database and categorized according to the presence of obesity (body mass index [BMI] >30 kg/m2) and overweight/normal BMI (BMI≤30 kg/m2). There were 18 individuals with obesity (BMI 36.4±3 kg/m2) and 59 (BMI 24.1±3.6 kg/m2) with overweight/normal BMI. Peak oxygen consumption (VO2) on noninvasive cardiopulmonary exercise testing was lower in patients with obesity (15.6±3.5 vs 19.6±5.8 ml/kg/min, p=0.04). At rest, systemic flow (Qs) (7.0 [4.8; 8.3] vs 4.8 [3.9; 5.8] l/min, p=0.001), pulmonary artery (PA) pressure (16.3±3.5 vs 13.1±3.5 mmHg, p=0.002), and PA wedge pressure (PAWP) (11.7±4.4 vs 8.9±3.1 mmHg, p=0.01) were higher, while arterial O2 saturation was lower (89.5% [86.5; 92.3] vs 93% [90; 95]) in obesity compared to overweight/normal BMI. Similarly, patients with obesity had higher exercise PA pressure (29.7±6.5 vs 24.7±6.8 mmHg, p=0.01) and PAWP (23.0±6.5 vs 19.8±7.3 mmHg, p=0.047), but lower arterial O2 saturation (82.4±7.0% vs 89% [85; 92], p=0.003). Adults post-Fontan with obesity have worse aerobic capacity, increased Qs, higher filling pressures, and decreased arterial O2 saturation compared to those with overweight/normal BMI, both at rest and during exercise, mirroring the findings observed in the obesity phenotype of heart failure with preserved ejection fraction. Whether treating obesity and its cardiometabolic sequelae in Fontan patients will improve hemodynamics and outcomes requires further study.

The role of the heart in the evolution of aerobic performance.

Aerobic metabolism underlies vital traits such as locomotion and thermogenesis, and aerobic capacity influences fitness in many animals. The heart is a key determinant of aerobic capacity, but the relative influence of cardiac output versus other steps in the O2 transport pathway remains contentious. In this Commentary, we consider this issue by examining the mechanistic basis for adaptive increases in aerobic capacity (thermogenic V̇O2,max; also called summit metabolism) in deer mice (Peromyscus maniculatus) native to high altitude. Thermogenic V̇O2,max is increased by acclimation to cold hypoxia (simulating high-altitude conditions), and high-altitude populations generally have greater V̇O2,max than their low-altitude counterparts. This plastic and evolved variation in V̇O2,max is associated with corresponding variation in maximal cardiac output, along with variation in other traits across the O2 pathway (e.g. arterial O2 saturation, blood haemoglobin content and O2 affinity, tissue O2 extraction, tissue oxidative capacity). By applying fundamental principles of gas exchange, we show that the relative influence of cardiac output on V̇O2,max depends on the O2 diffusing capacity of thermogenic tissues (skeletal muscles and brown adipose tissues). Functional interactions between cardiac output and blood haemoglobin content determine circulatory O2 delivery and thus affect V̇O2,max, particularly in high-altitude environments where erythropoiesis can increase haematocrit and blood viscosity. There may also be functional linkages between cardiac output and tissue O2 diffusion due to the role of blood flow in determining capillary haematocrit and red blood cell flux. Therefore, the functional interactions between cardiac output and other traits in the O2 pathway underlie the adaptive evolution of aerobic capacities.

Examining the Influence of Cognitive Load and Environmental Conditions on Autonomic Nervous System Response in Military Aircrew: A Hypoxia-Normoxia Study.

Executing flight operations demand that military personnel continuously perform tasks that utilize low- and high-order cognitive functions. The autonomic nervous system (ANS) is crucial for regulating the supply of oxygen (O2) to the brain, but it is unclear how sustained cognitive loads of different complexities may affect this regulation. Therefore, in the current study, ANS responses to low and high cognitive loads in hypoxic and normoxic conditions were evaluated. The present analysis used data from a previously conducted, two-factor experimental design. Healthy subjects (n = 24) aged 19 to 45 years and located near Fort Novosel, AL, participated in the parent study. Over two, 2-h trials, subjects were exposed to hypoxic (14.0% O2) and normoxic (21.0% O2) air while simultaneously performing one, 15-min and one, 10-min simulation incorporating low- and high-cognitive aviation-related tasks, respectively. The tests were alternated across five, 27-min epochs; however, only epochs 2 through 4 were used in the analyses. Heart rate (HR), HR variability (HRV), and arterial O2 saturation were continuously measured using the Warfighter MonitorTM (Tiger Tech Solutions, Inc., Miami, FL, USA), a previously validated armband device equipped with electrocardiographic and pulse oximetry capabilities. Analysis of variance (ANOVA) regression models were performed to compare ANS responses between the low- and high-cognitive-load assessments under hypoxic and normoxic conditions. Pairwise comparisons corrected for familywise error were performed using Tukey's test within and between high and low cognitive loads under each environmental condition. Across epochs 2 through 4, in both the hypoxic condition and the normoxic condition, the high-cognitive-load assessment (MATB-II) elicited heightened ANS activity, reflected by increased HR (+2.4 ± 6.9 bpm) and decreased HRV (-rMSSD: -0.4 ± 2.7 ms and SDNN: -13.6 ± 14.6 ms). Conversely, low cognitive load (ADVT) induced an improvement in ANS activity, with reduced HR (-2.6 ± 6.3 bpm) and increased HRV (rMSSD: +1.8 ± 6.0 ms and SDNN: vs. +0.7 ± 6.3 ms). Similar observations were found for the normoxic condition, albeit to a lower degree. These within-group ANS responses were significantly different between high and low cognitive loads (HR: +5.0 bpm, 95% CI: 2.1, 7.9, p < 0.0001; rMSSD: -2.2 ms, 95% CI: -4.2, -0.2, p = 0.03; SDNN: -14.3 ms, 95% CI: -18.4, -10.1, p < 0.0001) under the hypoxic condition. For normoxia, significant differences in ANS response were only observed for HR (+4.3 bpm, 95% CI: 1.2, 7.4, p = 0.002). Lastly, only high cognitive loads elicited significant differences between hypoxic and normoxic conditions but just for SDNN (-13.3 ms, 95% CI, -17.5, -8.9, p < 0.0001). Our study observations suggest that compared to low cognitive loads, performing high-cognitive-load tasks significantly alters ANS activity, especially under hypoxic conditions. Accounting for this response is critical, as military personnel during flight operations sustain exposure to high cognitive loads of unpredictable duration and frequency. Additionally, this is likely compounded by the increased ANS activity consequent to pre-flight activities and anticipation of combat-related outcomes.

Respiratory Syncytial Virus and Influenza Infections in Children in Ulaanbaatar, Mongolia, 2015-2021.

Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021. This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O2 saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT-PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray. Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2-6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p-value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases. In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity.

Influence of hemoglobin-O2 affnity on aerobic capacity in deer mice

High-altitude hypoxia can constrain tissue O2 supply, and several high-altitude populations and species have evolved adaptations to overcome this challenge. Evolved increases in hemoglobin-O2 (Hb-O2) affnity are pervasive across high-altitude taxa, but the influence of such increases on aerobic capacity (maximal O2 consumption) in hypoxia remains contentious. The influence of Hb-O2 affnity on aerobic capacity in hypoxia could vary depending on other traits in the O2 transport pathway, but this possibility is poorly understood. We examined this issue in deer mice ( Peromyscus maniculatus), which is found from sea level to &gt;4300m altitude in the Rocky Mountains. Mice from populations native to high altitude and low altitude were born and raised to adulthood in captivity. Low-altitude mice (n=14) were acclimated to warm (25°C) normoxia, and high-altitude mice (n=14) were acclimated to cold (5°C) hypoxia (~12 kPa O2) for 6 weeks, creating two groups with very different capacities for O2 transport in hypoxia. Aerobic capacity for thermogenesis (VO2max) was then measured in hypoxia after each of three pharmacological treatments to manipulate Hb-O2 affnity: saline (control); efaproxiral, a negative allosteric regulator that decreases Hb-O2 affnity; and sodium cyanate, which covalently modifies Hb and increases Hb-O2 affnity. In control conditions, high-altitude mice had higher VO2max and arterial O2 saturation (SaO2) in hypoxia and higher Hb-O2 affnity (lower P50) than low-altitude mice. Efaproxiral reduced SaO2 and led to similar decreases in VO2max in both populations. Sodium cyanate increased SaO2 in hypoxia in both populations. However, this was only associated with an increase in VO2max in 7 of 14 high-altitude mice and 4 of 14 low-altitude mice. Our results suggest that Hb-O2 affnity may be optimal for aerobic capacity in hypoxia in high-altitude mice, and that reductions in Hb-O2 affnity reduce performance. Supported by NSERC of Canada. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of lower body negative pressure on cardiac and cerebral function in postural orthostatic tachycardia syndrome: A pilot MRI assessment.

Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging. Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of -25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO2 ) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O2 saturation (SvO2 ; susceptometry-based oximetry), and arterial O2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p < 0.001) with no group differences (HC: +9 ± 8 bpm; POTS: +13 ± 11 bpm; p = 0.35). Biventricular volumes, SV, and Qc decreased during LBNP (p < 0.001). CBF and SvO2 decreased with LBNP (p = 0.01 and 0.03, respectively) but not cerebral VO2 (effect of LBNP: p = 0.28; HC: -0.2 ± 3.7 mL/min; POTS: +1.1 ± 2.0 mL/min; p = 0.33 between groups). Regional cerebral perfusion decreased during LBNP (p < 0.001) but was not different between groups. These data suggest patients with POTS have preserved cardiac and cerebrovascular function.

Respiratory Effects of Continuous Positive Airway Pressure Administered during Recovery from General Anesthesia in Brachycephalic Dogs.

This study aimed to evaluate the benefits of applying 5 cmH2O of CPAP using a pediatric helmet during the recovery phase from general anesthesia in brachycephalic dogs. Brachycephalic dogs undergoing various surgical procedures were included in this study, and a total of 64 subjects were randomly assigned to receive either standard oxygen supplementation (NO-CPAP group) or oxygen supplementation combined with CPAP (CPAP group). This study evaluated arterial blood pH, blood gas partial pressures of O2 and CO2, arterial blood O2 saturation, and related parameters during recovery. The dogs were monitored, and helmet tolerance was assessed using predefined criteria. Of the initially assessed 69 dogs, 64 were enrolled: 32 in the CPAP group and 32 in the NO-CPAP group. Fifteen dogs in the NO-CPAP group were excluded based on predetermined criteria. The CPAP group showed significant improvements in PaO2, PaO2/FiO2, P(A-a)O2, F-Shunt, and respiratory rate compared with the NO-CPAP group (p < 0.001). The incidence of reintubation and helmet intolerance was higher in the NO-CPAP group (18% and 15.6%, respectively) than in the CPAP group (0%). This study highlights the potential benefits of incorporating CPAP, delivered through a pediatric helmet, in the perioperative management of brachycephalic dogs.

Exercise catheterization in adults post-Fontan with normal and abnormal haemodynamic criteria: Insights into normal Fontan physiology.

The normal (i.e. expected) haemodynamics in adults post-Fontan remain poorly delineated. Moreover, the definitions of elevated exercise pulmonary artery (PA) and PA wedge pressure (PAWP) for this population have not been described. Seventy-two adults post-Fontan undergoing exercise catheterization were categorized into abnormal (Group I, n = 59; defined as resting mean PA ≥14 mmHg and/or PAWP ≥12 mmHg, ΔPAWP/Δsystemic flow [Qs] >2 mmHg/L/min, and/or ΔPA/Δpulmonary flow >3 mmHg/L/min) and normal (Group II, n = 13) haemodynamics. Thirty-nine patients with non-cardiac dyspnoea (NCD) were included as controls. There was no difference in exercise arterial oxygen saturation (87% [81-92] vs. 89% [85-93], p = 0.29), while exercise PA pressure (27 [23-31] vs. 16 [14.5-19.5] mmHg, p < 0.001) and PAWP were higher (21 [18-28] vs. 12 [8-14] mmHg, p < 0.001) in Group I. At peak exercise, Group I had lower heart rate (97 [81-120] vs. 133 [112.5-147.5] bpm, p < 0.001) and Qs response (67.3 [43.8-93.1] vs. 105.9 (82-118.5) % predicted, p < 0.001) than Group II. Exercise superior vena cava pressures were higher (16 [14-22.5] vs. 5.5 [3-7.3] mmHg, p < 0.001) and arterial oxygen saturation lower (89% [85-93] vs. 97% [96-98], p < 0.001) in Group II compared to NCD, while no differences in PAWP, stroke volume index, heart rate, or Qs response were seen. If defined as two standard deviations above mean values for Group II, elevated PAWP and mean PA pressure post-Fontan would correspond to 20.6 mmHg and 25.8 mmHg, respectively. PAWP >20 mmHg and mean PA pressure >25 mmHg could be used to define elevated values during exercise in adults post-Fontan. The major discrepancy in exercise haemodynamics among Group II compared to controls appears to be the degree of systemic venous hypertension and arterial desaturation.

Assessing amyloid plaque burden in aging marmosets and genetically engineered PSEN1 mutation carriers using 11C‐PiB PET

AbstractBackgroundThere is an urgent need to develop novel animal models to investigate the underlying cellular and molecular root causes of the pathogenesis and progression of AD. Our group has worked to establish the common marmoset as the first primate‐specific model of AD to reveal the earliest cellular and molecular events of AD processes and allow charting of AD progression from its inception. For this, we established a colony of outbred marmosets and used genetic engineering techniques to generate marmosets carrying the PSEN1‐C410Y and PSEN1‐A426P mutations that cause early‐onset, familial AD. The present study aims to use PET imaging to access and track the progression of Ab plaque burden non‐invasively and longitudinally in our marmoset models of AD.MethodMarmosets anesthetized with isoflurane delivered via a facemask were placed in a preclinical PET/CT scanner customized with marmoset‐specific beds. Respiratory rate, heart rate, arterial O2 saturation, and rectal temperature were monitored and maintained at normal physiological values. Our PET imaging protocol follows the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The amyloid‐binding 11C‐Pittsburgh Compound B (11C‐PiB) was delivered intravenously in doses varying from 18.5 – 185 MBq (0.5 – 5 mCi). A 90‐min dynamic acquisition was performed immediately following the radiotracer injection, followed by a 3D CT scan acquired at 200 µm isotropic resolution. After the PET/CT neuroimaging scan, the marmosets were recovered from anesthesia and returned to their home cages.ResultWe observed positive 11C‐PiB binding and retention in the brains of aging outbred marmosets and in marmosets harboring PSEN1 mutations. Significant 11C‐PiB retention was observed in the cortex and white matter tracts. The areas with the highest 11C‐PiB retention were the lateral frontal cortex, anterior cingulate cortex, and temporal lobe regions.ConclusionThis study demonstrates using 11C‐PiB to track Ab plaque burden in the brains of aging marmosets and marmosets harboring PSEN1 mutations. As observed in human patients of AD, the amount of 11C‐PiB bound (measured in SUV and SUVR units) varied from animal to animal, and we are currently performing group analysis to investigate the dependence of 11C‐PiB retention on age and sex. This research was funded by NIH/NIA grants R24AG073190 and U19AG074866.

Assessing amyloid plaque burden in aging marmosets and genetically engineered PSEN1 mutation carriers using 11C‐PiB PET

AbstractBackgroundThere is an urgent need to develop novel animal models to investigate the underlying cellular and molecular root causes of the pathogenesis and progression of AD. Our group has worked to establish the common marmoset as the first primate‐specific model of AD to reveal the earliest cellular and molecular events of AD processes and allow charting of AD progression from its inception. For this, we established a colony of outbred marmosets and used genetic engineering techniques to generate marmosets carrying the PSEN1‐C410Y and PSEN1‐A426P mutations that cause early‐onset, familial AD. The present study aims to use PET imaging to access and track the progression of Ab plaque burden non‐invasively and longitudinally in our marmoset models of AD.MethodMarmosets anesthetized with isoflurane delivered via a facemask were placed in a preclinical PET/CT scanner customized with marmoset‐specific beds. Respiratory rate, heart rate, arterial O2 saturation, and rectal temperature were monitored and maintained at normal physiological values. Our PET imaging protocol follows the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The amyloid‐binding 11C‐Pittsburgh Compound B (11C‐PiB) was delivered intravenously in doses varying from 18.5 – 185 MBq (0.5 – 5 mCi). A 90‐min dynamic acquisition was performed immediately following the radiotracer injection, followed by a 3D CT scan acquired at 200 µm isotropic resolution. After the PET/CT neuroimaging scan, the marmosets were recovered from anesthesia and returned to their home cages.ResultWe observed positive 11C‐PiB binding and retention in the brains of aging outbred marmosets and in marmosets harboring PSEN1 mutations. Significant 11C‐PiB retention was observed in the cortex and white matter tracts. The areas with the highest 11C‐PiB retention were the lateral frontal cortex, anterior cingulate cortex, and temporal lobe regions.ConclusionThis study demonstrates using 11C‐PiB to track Ab plaque burden in the brains of aging marmosets and marmosets harboring PSEN1 mutations. As observed in human patients of AD, the amount of 11C‐PiB bound (measured in SUV and SUVR units) varied from animal to animal, and we are currently performing group analysis to investigate the dependence of 11C‐PiB retention on age and sex.This research was funded by NIH/NIA grants R24AG073190 and U19AG074866.

Insulin resistance without coexisting hyperglycaemia is not independently associated with cardiorespiratory fitness or its components in women

Abstract Background Insulin resistance (IR) is a globally prevalent condition in which tissues’ response to insulin is diminished. Cardiorespiratory fitness (peak O2 uptake (VO2peak)) is determined by Fick’s equation (VO2 = cardiac output (CO) × arteriovenous O2 difference (Ca-vO2) = heart rate × stroke volume (SV) × Ca-vO2) and diffusion law (VO2 = diffusive O2 conductance (DO2) × constant k × venous O2 pressure (PvO2)). Several studies suggest an association between IR and decreased VO2peak, but the association has been questioned by analyses taking account of body size and composition, and potential mechanisms behind the association are unknown. Purpose To test a hypothesis that IR is not independently associated with VO2peak or its components. Methods Fifty of 144 women, who had participated in baseline experiments of three intervention studies, were included in this retrospective cross-sectional study; see Table 1 for subject characteristics. The inclusion criteria were age 18-40 years, body mass index 18.5-40 kg/m2, Caucasian origin, and available data on key measures. The exclusion criteria were diseases, medications, and other factors possibly affecting VO2peak. We measured haemoglobin, fasting glucose, and fasting insulin concentrations (blood), assessed IR (homeostasis model assessment (HOMA-IR)), and measured body size and composition (bioimpedance). The subjects performed an incremental cycling test to volitional fatigue; we measured ventilatory gas exchange (spiroergometry), arterial O2 saturation (oximetry), and SV and CO (impedance cardiography), and calculated Ca-vO2, DO2, and PvO2. We analysed VO2peak and its components as absolute (e.g. L/min) and ratiometrically scaled values (e.g. mL/min/kg), and when appropriate, also as allometrically scaled values (e.g. mL/min/kg^x, where 0 &amp;lt; x &amp;lt; 1) after identifying optimal variable-specific exponents. Results VO2peak scaled to body mass (BM) as well as SVpeak and COpeak scaled to body surface area (BSA) were inversely associated with the body size variables they were scaled to (all P &amp;lt; 0.013). Contrariwise, this was not the case when we optimally scaled VO2peak to fat-free mass (FFM), SVpeak to FFM^0.55, COpeak to FFM^0.50, and DO2peak to FFM (all 0.066 &amp;lt; P &amp;lt; 0.977). HOMA-IR was inversely associated with VO2peak scaled to BM but not in a multivariate analysis, whereas HOMA-IR was not associated with VO2peak scaled to FFM (Table 2); we made alike observations with SVpeak and COpeak (data not shown). Further, VO2peak scaled to BM as well as SVpeak and COpeak scaled to BSA were or tended to be up to 15 % higher in a group with HOMA-IR&amp;lt;3.0 than in a group with HOMA-IR≥3.0, while other peak exercise data did not differ between the groups (Table 1). Conclusion Body size and composition significantly affect conclusions drawn regarding VO2peak and its components. Taking this into account, IR without coexisting hyperglycaemia is not independently associated with VO2peak or its components in women.Table 1Table 2

Physiological and skeletal muscle responses to high-intensity interval exercise in Thoroughbred horses.

The purpose of this study was to determine whether acute high-intensity interval exercise or sprint interval exercise induces greater physiological and skeletal muscle responses compared to moderate-intensity continuous exercise in horses. In a randomized crossover design, eight trained Thoroughbred horses performed three treadmill exercise protocols consisting of moderate-intensity continuous exercise (6 min at 70% VO2max; MICT), high-intensity interval exercise (6 × 30 s at 100% VO2max; HIIT), and sprint interval exercise (6 × 15 s at 120% VO2max; SIT). Arterial blood samples were collected to measure blood gas variables and plasma lactate concentration. Biopsy samples were obtained from the gluteus medius muscle before, immediately after, 4 h, and 24 h after exercise for biochemical analysis, western blotting and real-time RT-PCR. Effects of time and exercise protocol were analyzed using mixed models (p < 0.05). Heart rate and plasma lactate concentration at the end of exercise were higher in HIIT and SIT than those in MICT (heart rate, HIIT vs. MICT, p = 0.0005; SIT vs. MICT, p = 0.0015; lactate, HIIT vs. MICT, p = 0.0014; SIT vs. MICT, p = 0.0003). Arterial O2 saturation and arterial pH in HIIT and SIT were lower compared with MICT (SaO2, HIIT vs. MICT, p = 0.0035; SIT vs. MICT, p = 0.0265; pH, HIIT vs. MICT, p = 0.0011; SIT vs. MICT, p = 0.0023). Muscle glycogen content decreased significantly in HIIT (p = 0.0004) and SIT (p = 0.0016) immediately after exercise, but not in MICT (p = 0.19). Phosphorylation of AMP-activated protein kinase (AMPK) in HIIT showed a significant increase immediately after exercise (p = 0.014), but the increase was not significant in MICT (p = 0.13) and SIT (p = 0.39). At 4 h after exercise, peroxisome proliferator-activated receptor γ co-activator-1α mRNA increased in HIIT (p = 0.0027) and SIT (p = 0.0019) and vascular endothelial growth factor mRNA increased in SIT (p = 0.0002). Despite an equal run distance, HIIT and SIT cause more severe arterial hypoxemia and lactic acidosis compared with MICT. In addition, HIIT activates the AMPK signaling cascade, and HIIT and SIT elevate mitochondrial biogenesis and angiogenesis, whereas MICT did not induce any significant changes to these signaling pathways.

Abstract 12910: Exercise Hemodynamics Unmasks Stage C Heart Failure With Preserved Ejection Fraction and Impaired Peripheral Oxygen Extraction in Stage A/B Patients in a Safety-Net Center

Introduction: There is a gap in research evaluating hemodynamics and impaired peripheral oxygen extraction in Stage A/B HFpEF in diverse groups. We sought to characterize the prevalence of impaired cardiac/peripheral profiles in Stage A/B HFpEF at Boston Medical Center. Hypothesis: We hypothesize both abnormal cardiac and peripheral profiles will be unmasked in exercising Stage A/B HFpEF patients. Methods: Invasive cardiopulmonary exercise testing (iCPET) was performed in 30 individuals with Stage A/B HFpEF. Significant valvular or pulmonary disease were excluded. Criteria for an impaired cardiac profile, with reclassification to Stage C, included exercise PCWP ≥ 25 mmHg or ΔPCWP/ΔCO slope &gt; 2 mmHg/L/min. An impaired peripheral profile was defined as O 2 extraction ratio (peak arterio-venous oxygen saturation difference)/ (1.34*rest hemoglobin*rest arterial O 2 saturation) &lt; 50%. With an approved IRB, the analysis was conducted in R. Results: Cohort clinical data shown in Table with 47% non-white and 57% female patients. Exercise unmasked Stage C HFpEF in 23 (77%) of cases; 17% had an impaired peripheral profile (O 2 extraction ratio 43 ± 7) and 10% (3 out of 30 patients) had concomitant impaired cardiac and peripheral profiles. Both cardiac and peripheral metrics correlated to metabolic parameters: peak oxygen consumption correlated to PCWP (rho -0.52, p&lt;0.004) and extraction ratio correlated to oxygen-uptake efficiency slope (rho 0.40, p=0.029). Conclusions: In our diverse cohort, a significant proportion of Stage A/B patients reclassified to Stage C HFpEF via invasive exercise testing; abnormal peripheral profiles were also noted. Impaired cardiac and peripheral profile metrics were related to metabolic parameters. Broader implementation of iCPET in early disease stages and attention to both cardiac and peripheral profiles in diverse populations will guide further HFpEF research in novel mechanisms and therapeutics.

Liver Fibrosis Scores Are Associated With Resting and Exercise Fontan and Pulmonary Artery Wedge Pressures: Insights Into FALD.

Alterations in liver perfusion and venous hypertension have been implicated in the pathophysiology of Fontan-associated liver disease (FALD). However, the correlation between exercise hemodynamics and markers of FALD have not been studied. We performed a retrospective review of 32 consecutive adults undergoing exercise catheterisation at the Mayo Clinic, Minnesota. Invasive hemodynamics were correlated with aspartate transaminase to platelet ratio index (APRI) and the Fibrosis-4 (Fib-4) score, well validated surrogates of liver fibrosis. The mean age was 30.9 ± 7 years. The mean APRI was 0.5±0.2 and the mean Fib-4 score 1.3 ± 0.8. Fib-4 scores correlated with spleen size on abdominal imaging (r= 0.40; P= 0.03). Resting Fontan pressure was 13.9 ± 3.9 mm Hg and pulmonary artery wedge pressure (PAWP) 10.0 ± 3.5 mm Hg. At peak exercise (69.4 ± 23.2 W), Fontan pressures increased to 26.5 ± 6.2 mm Hg and PAWP to 22.4±7.1 mm Hg. APRI and Fib-4 score were directly related to Fontan pressure and PAWP at rest and during exercise, and inversely related to exercise arterial O2 saturation. Fib-4 inversely correlated with O2 delivery indices. Similarly, when categorising patients according to high APRI (>0.5 vs ≤ 0.5) or Fib-4 score (≥ 1.45 vs < 1.45) according to previously proposed cutoffs for diagnosis of liver fibrosis, those with elevated scores had higher resting and exercise Fontan and PAWP pressure with lower O2 arterial saturation. ARPI and Fib-4 score correlated with resting and exercise Fontan pressure and PAWP. In addition, Fib-4 scores were inversely related to O2 delivery indices. These findings support a role played by hepatic venous hypertension and reduced O2 supply in patients with FALD.

Respiratory support with nasal high flow without supplemental oxygen in patients undergoing endoscopic retrograde cholangiopancreatography under moderate sedation: a prospective, randomized, single-center clinical trial

BackgroundNasal high flow (NHF) may reduce hypoxia and hypercapnia during an endoscopic retrograde cholangiopancreatography (ERCP) procedure under sedation. The authors tested a hypothesis that NHF with room air during ERCP may prevent intraoperative hypercapnia and hypoxemia.MethodsIn the prospective, open-label, single-center, clinical trial, 75 patients undergoing ERCP performed with moderate sedation were randomized to receive NHF with room air (40 to 60 L/min, n = 37) or low-flow O2 via a nasal cannula (1 to 2 L/min, n = 38) during the procedure. Transcutaneous CO2, peripheral arterial O2 saturation, a dose of administered sedative and analgesics were measured.ResultsThe primary outcome was the incidence of marked hypercapnia during an ERCP procedure under sedation observed in 1 patient (2.7%) in the NHF group and in 7 patients (18.4%) in the LFO group; statistical significance was found in the risk difference (-15.7%, 95% CI -29.1 – -2.4, p = 0.021) but not in the risk ratio (0.15, 95% CI 0.02 – 1.13, p = 0.066).In secondary outcome analysis, the mean time-weighted total PtcCO2 was 47.2 mmHg in the NHF group and 48.2 mmHg in the LFO group, with no significant difference (-0.97, 95% CI -3.35 – 1.41, p = 0.421). The duration of hypercapnia did not differ markedly between the two groups either [median (range) in the NHF group: 7 (0 – 99); median (range) in the LFO group: 14.5 (0 – 206); p = 0.313] and the occurrence of hypoxemia during an ERCP procedure under sedation was observed in 3 patients (8.1%) in the NHF group and 2 patients (5.3%) in the LFO group, with no significant difference (p = 0.674).ConclusionsRespiratory support by NHF with room air did not reduce marked hypercapnia during ERCP under sedation relative to LFO. There was no significant difference in the occurrence of hypoxemia between the groups that may indicate an improvement of gas exchanges by NHF.Trial registrationjRCTs072190021.The full date of first registration on jRCT: August 26, 2019.

Study of Correlation of Arterial Blood Gas Measurements with Peripheral Venous Blood Gas Values in Adult Patients Admitted in ICU in Tertiary Care Hospital in Central India – A Cross-Sectional Study

Objectives: Arterial blood gas (ABG) analysis is an essential investigation for assessment of ventilation, oxygenation and acid–base status in critically ill patients. Arterial puncture to obtain arterial blood is more invasive procedure than venous and has more potential complications. The present study was undertaken to find out the correlation between arterial and peripheral venous blood gas (VBG) values for PO2 (Partial pressure of oxygen), PCO2 (Partial pressure of carbon dioxide), pH (Potential of hydrogen) and HCO3 (bicarbonates). Material and Methods: A total of 131 consecutive patients admitted to intensive care unit (ICU) requiring ABG analysis to determine their acid–base status or ventilatory status were included in the study. Arterial and venous blood samples were obtained with a heparinised syringe within &lt;15 min, after performing modified Allen’s test and were analysed using blood gas analysis machine. The mean of pH, pCO2, HCO3, and PO2, values in arterial and venous samples was determined, along with peripheral arterial oxygen saturation (SpO2) of patients. Results: ABG and VBG analysis correlated well for pH, pCO2 and HCO3, as their correlation coefficient (r) were 0.976, 0.992 and 0.984, respectively, whereas PO2 has correlation coefficient of 0.010 which suggests that there was poor correlation in PO2. For each unit increase in pCO2, pH and HCO3 of VBG, all these ABG changes by 0.9831 units, 0.914 units and 0.992 units, respectively. Peripheral O2 saturation (SpO2) correlates well with arterial O2 saturation, however, does not correlate with venous O2 saturation. Conclusion: The results show that VBG analysis can be a substitute for ABG for evaluation of ventilatory function and acid–base imbalance for pH, pCO2 and HCO3 in patients of ICU setup in many clinical contexts.

Effect of high ambient temperature on physiological responses during incremental exercise in Thoroughbred horses

Several reports have suggested that the risk of exertional heat illness (EHI) in Thoroughbred racehorses increases in high ambient temperatures. Heat dissipation in horses during exercise becomes less efficient when the body temperature and ambient temperature are close. Therefore, we hypothesised that exercise at 40 °C may increase body temperature, oxygen consumption, and cardiac output during incremental exercise tests compared to 20 and 30 °C. Six trained Thoroughbred horses were studied in a randomised, crossover design at three ambient temperatures with a 6-day washout period. Using a 3% inclined treadmill, horses performed incremental exercise tests at 1.7, 3.5, 6, 8, and 10 m/s for 90 s at ambient temperatures of 20, 30, and 40 °C. The effects of ambient temperature at 10 m/s on physiological variables were analysed using mixed models (P&lt;0.05). Pulmonary arterial temperature and rectal temperature at 40 °C were higher than those at 20 °C (P&lt;0.001) and 30 °C (P&lt;0.001). Similarly, oxygen consumption (vs 20 °C, P=0.009; vs 30 °C, P=0.006) and cardiac output (vs 20 °C, P=0.001; vs 30 °C, P=0.001) at 40 °C were higher than those at 20 and 30 °C. Arterial O2 partial pressure, O2 saturation, and pH at 40 °C were lower than those at 20 and 30 °C. Arterial CO2 partial pressure at 40 °C was higher than that at 20 and 30 °C. No differences were observed in arterial-mixed venous O2 concentration difference (P=0.391) and plasma lactate concentration (P=0.134) at different ambient temperatures. These results indicate that exercise at 40 °C causes excessive high body temperature, decreased running economy, and increased cardiac output compared to exercise at 20 and 30 °C. We strongly suggest that trainers and veterinarians should anticipate the occurrence of increased thermal stresses when ambient temperature is extremely high even in dry conditions and prepare to mitigate the risk of EHI from the perspective of equine welfare.

393 PERIODIC BREATHING: WHAT HAPPENS IN THE MUSCLE?

Abstract Periodic breathing (PB) is a recognized sign of poor prognosis in heart failure (HF). It is defined as a cyclic fluctuation of minute ventilation, and oxygen uptake (V̇O2) and carbon dioxide elimination (V̇CO2) at the lungs. It is unknow whether PB influences O2 availability in the cardiac, respiratory and locomotor muscles. To evaluate whether O2 availability at the muscles was affected by PB, we measured at rest, continuously and simultaneously, ventilation, ventilatory gas exchange, arterial hemoglobin O2 saturation and oxygenated/deoxygenated haemoglobin (O2Hb/HHb) content over the quadriceps by near infra-red spectroscopy (NIRS) in a patient with severe HF due to a dilated cardiomyopathy with severe biventricular dysfunction with PB at rest. NIRS application in clinical medicine started after the observation that biological tissues are quite transparent to light in the near infrared spectrum (i.e.700-1,300 nm), the second critical element that enables the use of NIRS is the oxygenation-dependent light absorbing characteristics of haemoglobin (Hb): by applying different light impulse wavelengths, the relative changes in O2Hb and HHb concentration in skeletal muscle can be monitored. The left panel shows cyclic fluctuation of ventilation, V̇O2, V̇CO2, PetO2 and PetCO2 patterns, which are partially out of phase between each other and respiratory exchange ratio pattern, and haemoglobin O2 saturation shows a cyclic pattern (95-90%). The cycle length of ventilation was 110 ± 6 s with an amplitude of 28.9 ± 5.1 l/min. NIRS (upper right panel) shows a directionally opposite fluctuation of O2Hb and HHb with a cycle length similar to that observed with ventilation. The average fluctuation on 6 consecutive cycles was 2.95% ± 0.27 (p&amp;lt;0.0001) and 2.73% ± 0.27 (p&amp;lt;0.0001) for O2Hb and HHb respectively. Total Hb was not significantly affected by PB in the muscle, 0.22%±0.38 (p=ns). The present study is the first recording of periodic oscillations of O2 saturated and desaturated Hb concentration at the muscular level at rest in a patient with severe HF and PB: we speculate that the cyclic ventilatory pattern is responsible for a cycling of ventilation and perfusion coupling in the lung. This so-called ventilation/perfusion mismatch induces cyclic fluctuation of blood flow to perfused but unventilated or poorly ventilated (shunt and low V̇A/Q) lung zones and to unperfused or poorly perfused (high V̇A/Q and dead space) ventilated lung zones.

Development and validation of a mathematical model to simulate human cardiovascular and respiratory responses to battlefield trauma.

Mathematical models of human cardiovascular and respiratory systems provide a viable alternative to generate synthetic data to train artificial intelligence (AI) clinical decision-support systems and assess closed-loop control technologies, for military medical applications. However, existing models are either complex, standalone systems that lack the interface to other applications or fail to capture the essential features of the physiological responses to the major causes of battlefield trauma (i.e., hemorrhage and airway compromise). To address these limitations, we developed the cardio-respiratory (CR) model by expanding and integrating two previously published models of the cardiovascular and respiratory systems. We compared the vital signs predicted by the CR model with those from three models, using experimental data from 27 subjects in five studies, involving hemorrhage, fluid resuscitation, and respiratory perturbations. Overall, the CR model yielded relatively small root mean square errors (RMSEs) for mean arterial pressure (MAP; 20.88 mm Hg), end-tidal CO2 (ETCO2 ; 3.50 mm Hg), O2 saturation (SpO2 ; 3.40%), and arterial O2 pressure (PaO2 ; 10.06 mm Hg), but a relatively large RMSE for heart rate (HR; 70.23 beats/min). In addition, the RMSEs for the CR model were 3% to 10% smaller than the three other models for HR, 11% to 15% for ETCO2 , 0% to 33% for SpO2 , and 10% to 64% for PaO2 , while they were similar for MAP. In conclusion, the CR model balances simplicity and accuracy, while qualitatively and quantitatively capturing human physiological responses to battlefield trauma, supporting its use to train and assess emerging AI and control systems.

Aqp5-/- mice exhibit reduced maximal body O2 consumption under cold exposure, normal pulmonary gas exchange, and impaired formation of brown adipose tissue.

The fundamental body functions that determine maximal O2 uptake (V̇o2max) have not been studied in Aqp5-/- mice (aquaporin 5, AQP5). We measured V̇o2max to globally assess these functions and then investigated why it was found altered in Aqp5-/- mice. V̇o2max was measured by the Helox technique, which elicits maximal metabolic rate by intense cold exposure of the animals. We found V̇o2max reduced in Aqp5-/- mice by 20%-30% compared with wild-type (WT) mice. As AQP5 has been implicated to act as a membrane channel for respiratory gases, we studied whether this is caused by the known lack of AQP5 in the alveolar epithelial membranes of Aqp5-/- mice. Lung function parameters as well as arterial O2 saturation were normal and identical between Aqp5-/- and WT mice, indicating that AQP5 does not contribute to pulmonary O2 exchange. The cause for the decreased V̇o2max thus might be found in decreased O2 consumption of an intensely O2-consuming peripheral organ such as activated brown adipose tissue (BAT). We found indeed that absence of AQP5 greatly reduces the amount of interscapular BAT formed in response to 4 wk of cold exposure, from 63% in WT to 25% in Aqp5-/- animals. We conclude that lack of AQP5 does not affect pulmonary O2 exchange, but greatly inhibits transformation of white to brown adipose tissue. As under cold exposure, BAT is a major source of the animals' heat production, reduction of BAT likely causes the decrease in V̇o2max under this condition.