Wagner diagram for modeling O2pathway - calculation and graphical display by the Helsinki O2pathway tool.

OBJECTIVE: Maximal O2uptake (V̇O2max) reflects the individual's maximal rate of O2transport and utilization through the integrated whole-body pathway composed of the lungs, heart, blood, circulation, and metabolically active tissues. As such, V̇O2maxis strongly associated with physical capacity as well as overall health and thus acts as one predictor of physical performance and as a vital sign in determination of status and progress of numerous clinical conditions. Quantifying the contribution of single parts of the multistep O2pathway to V̇O2maxprovides mechanistic insights into exercise (in)tolerance and into therapy-, training-, or disuse-induced adaptations at individual or group levels. We developed a desktop application (Helsinki O2Pathway Tool - HO2PT) to model numerical and graphical display of the O2pathway based on the "Wagner diagram" originally formulated by Peter D. Wagner and his colleagues. Approach: The HO2PT was developed and programmed in Python to integrate the Fick principle and Fick's law of diffusion into a computational system to import, calculate, graphically display, and export variables of the Wagner diagram. Main results: The HO2PT models O2pathway both numerically and graphically according to the Wagner diagram and pertains to conditions under which the mitochondrial oxidative capacity of metabolically active tissues exceeds the capacity of the O2transport system to deliver O2to the mitochondria. The tool is based on the Python open source code and libraries and freely and publicly available online for Windows, macOS, and Linux operating systems. Significance: The HO2PT offers a novel functional and demonstrative platform for those interested in examining V̇O2maxand its determinants by using the Wagner diagram. It will improve access to and usability of Wagner's and his colleagues' integrated physiological model and thereby benefit users across the wide spectrum of contexts such as scientific research, education, exercise testing, sports coaching, and clinical medicine. .

Cardiorespiratory fitness is linked with heart rate variability during stress in "at-risk" adults.

BACKGROUND: Physiological mechanisms explaining why cardiorespiratory fitness (CRF) predicts cardiovascular morbidity and mortality are incompletely understood. We examined if CRF modifies vagally mediated heart rate variability (HRV) during acute physical or psychosocial stress or night-time sleep in adults with cardiovascular risk factors. METHODS: Seventy-eight adults (age 56 years [IQR 50-60], 74% female, body mass index 28 kg/m2 [IQR 25-31]) with frequent cardiovascular risk factors participated in this cross-sectional study. They went through physical (treadmill cardiopulmonary exercise test [CPET]) and psychosocial (Trier Social Stress Test for Groups [TSST-G]) stress tests and night-time sleep monitoring (polysomnography). Heart rate (HR) and vagally mediated HRV (root mean square of successive differences between normal R-R intervals [RMSSD]) were recorded during the experiments and analyzed by taking account of potential confounders. RESULTS: CRF (peak O2 uptake) averaged 99% (range 78-126) in relation to reference data. From pre-rest to moderate intensities during CPET and throughout TSST-G, HR did not differ between participants with CRF below median (CRFlower) and CRF equal to or above median (CRFhigher), whereas CRFhigher had higher HRV than CRFlower, and CRF correlated positively with HRV in all participants. Meanwhile, CRF had no independent associations with HR or HRV levels during slow-wave sleep, the presence of metabolic syndrome was not associated with recorded HR or HRV levels, and single factors predicted HRV responsiveness independently only to limited extents. CONCLUSIONS: CRF is positively associated with prevailing vagally mediated HRV at everyday levels of physical and psychosocial stress in adults with cardiovascular risk factors.

Cardiorespiratory Fitness Estimation Based on Heart Rate and Body Acceleration in Adults With Cardiovascular Risk Factors: Validation Study.

BACKGROUND: Cardiorespiratory fitness (CRF) is an independent risk factor for cardiovascular morbidity and mortality. Adding CRF to conventional risk factors (eg, smoking, hypertension, impaired glucose metabolism, and dyslipidemia) improves the prediction of an individual's risk for adverse health outcomes such as those related to cardiovascular disease. Consequently, it is recommended to determine CRF as part of individualized risk prediction. However, CRF is not determined routinely in everyday clinical practice. Wearable technologies provide a potential strategy to estimate CRF on a daily basis, and such technologies, which provide CRF estimates based on heart rate and body acceleration, have been developed. However, the validity of such technologies in estimating individual CRF in clinically relevant populations is poorly known. OBJECTIVE: The objective of this study is to evaluate the validity of a wearable technology, which provides estimated CRF based on heart rate and body acceleration, in working-aged adults with cardiovascular risk factors. METHODS: In total, 74 adults (age range 35-64 years; n=56, 76% were women; mean BMI 28.7, SD 4.6 kg/m2) with frequent cardiovascular risk factors (eg, n=64, 86% hypertension; n=18, 24% prediabetes; n=14, 19% type 2 diabetes; and n=51, 69% metabolic syndrome) performed a 30-minute self-paced walk on an indoor track and a cardiopulmonary exercise test on a treadmill. CRF, quantified as peak O2 uptake, was both estimated (self-paced walk: a wearable single-lead electrocardiogram device worn to record continuous beat-to-beat R-R intervals and triaxial body acceleration) and measured (cardiopulmonary exercise test: ventilatory gas analysis). The accuracy of the estimated CRF was evaluated against that of the measured CRF. RESULTS: Measured CRF averaged 30.6 (SD 6.3; range 20.1-49.6) mL/kg/min. In all participants (74/74, 100%), mean difference between estimated and measured CRF was -0.1 mL/kg/min (P=.90), mean absolute error was 3.1 mL/kg/min (95% CI 2.6-3.7), mean absolute percentage error was 10.4% (95% CI 8.5-12.5), and intraclass correlation coefficient was 0.88 (95% CI 0.80-0.92). Similar accuracy was observed in various subgroups (sexes, age, BMI categories, hypertension, prediabetes, and metabolic syndrome). However, mean absolute error was 4.2 mL/kg/min (95% CI 2.6-6.1) and mean absolute percentage error was 16.5% (95% CI 8.6-24.4) in the subgroup of patients with type 2 diabetes (14/74, 19%). CONCLUSIONS: The error of the CRF estimate, provided by the wearable technology, was likely below or at least very close to the clinically significant level of 3.5 mL/kg/min in working-aged adults with cardiovascular risk factors, but not in the relatively small subgroup of patients with type 2 diabetes. From a large-scale clinical perspective, the findings suggest that wearable technologies have the potential to estimate individual CRF with acceptable accuracy in clinically relevant populations.

Measuring psychosocial stress with heart rate variability-based methods in different health and age groups.

Objective.Autonomic nervous system function and thereby bodily stress and recovery reactions may be assessed by wearable devices measuring heart rate (HR) and its variability (HRV). So far, the validity of HRV-based stress assessments has been mainly studied in healthy populations. In this study, we determined how psychosocial stress affects physiological and psychological stress responses in both young (18-30 years) and middle-aged (45-64 years) healthy individuals as well as in patients with arterial hypertension and/or either prior evidence of prediabetes or type 2 diabetes. We also studied how an HRV-based stress index (Relax-Stress Intensity, RSI) relates to perceived stress (PS) and cortisol (CRT) responses during psychosocial stress.Approach.A total of 197 participants were divided into three groups: (1) healthy young (HY,N = 63), (2) healthy middle-aged (HM,N = 61) and (3) patients with cardiometabolic risk factors (Pts,N = 73, 32-65 years). The participants underwent a group version of Trier Social Stress Test (TSST-G). HR, HRV (quantified as root mean square of successive differences of R-R intervals, RMSSD), RSI, PS, and salivary CRT were measured regularly during TSST-G and a subsequent recovery period.Main results.All groups showed significant stress reactions during TSST-G as indicated by significant responses of HR, RMSSD, RSI, PS, and salivary CRT. Between-group differences were also observed in all measures. Correlation and regression analyses implied RSI being the strongest predictor of CRT response, while HR was more closely associated with PS.Significance.The HRV-based stress index mirrors responses of CRT, which is an independent marker for physiological stress, around TSST-G. Thus, the HRV-based stress index may be used to quantify physiological responses to psychosocial stress across various health and age groups.

Altered Expiratory Flow Dynamics at Peak Exercise in Adult Men With Well-Controlled Type 1 Diabetes.

Type 1 diabetes may, in time, cause lung dysfunction including airflow limitation. We hypothesized that ventilatory flow morphology during a cardiopulmonary exercise test (CPET) would be altered in adult men with well-controlled type 1 diabetes. Thirteen men with type 1 diabetes [glycated hemoglobin A1c 59 (9) mmol/mol or 7.5 (0.8)%, duration of diabetes 12 (9) years, and age 33.9 (6.6) years] without diagnosed diabetes-related complications and 13 healthy male controls [age 37.2 (8.6) years] underwent CPET on a cycle ergometer (40 W increments every 3 min until volitional fatigue). We used a principal component analysis based method to quantify ventilatory flow dynamics throughout the CPET protocol. Last minute of each increment, peak exercise, and recovery were examined using linear mixed models, which accounted for relative peak oxygen uptake and minute ventilation. The type 1 diabetes participants had lower expiratory peak flow (P = 0.008) and attenuated slope from expiration onset to expiratory peak flow (P = 0.012) at peak exercise when compared with the healthy controls. Instead, during submaximal exercise and recovery, the type 1 diabetes participants possessed similar ventilatory flow dynamics to that of the healthy controls. In conclusion, men with relatively well-controlled type 1 diabetes and without clinical evidence of diabetes-related complications exhibited attenuated expiratory flow at peak exercise independently of peak oxygen uptake and minute ventilation. This study demonstrates that acute exercise reveals alterations in ventilatory function in men with type 1 diabetes but not until peak exercise.

Tooth Clenching Induces Abnormal Cerebrovascular Responses in Migraineurs.

Prevalence of masticatory parafunctions, such as tooth clenching and grinding, is higher among migraineurs than non-migraineurs, and masticatory dysfunctions may aggravate migraine. Migraine predisposes to cerebrovascular disturbances, possibly due to impaired autonomic vasoregulation, and sensitization of the trigeminovascular system. The relationships between clenching, migraine, and cerebral circulation are poorly understood. We used Near-Infrared Spectroscopy to investigate bilateral relative oxy- (%Δ[O2Hb]), deoxy- (%Δ[HHb]), and total (%Δ[tHb]) hemoglobin concentration changes in prefrontal cortex induced by maximal tooth clenching in twelve headache-free migraineurs and fourteen control subjects. From the start of the test, migraineurs showed a greater relative increase in right-side %Δ[HHb] than controls, who showed varying reactions, and right-side increase in %Δ[tHb] was also greater in migraineurs (p < 0.001 and p < 0.05, respectively, time-group interactions, Linear mixed models). With multivariate regression model, migraine predicted the magnitude of maximal blood pressure increases, associated in migraineurs with mood scores and an intensity of both headache and painful signs of temporomandibular disorders (pTMD). Although changes in circulatory parameters predicted maximal NIRS responses, the between-group differences in the right-side NIRS findings remained significant after adjusting them for systolic blood pressure and heart rate. A family history of migraine, reported by all migraineurs and four controls, also predicted maximal increases in both %Δ[HHb] and %Δ[tHb]. Presence of pTMD, revealed in clinical oral examination in eight migraineurs and eight controls, was related to maximal %Δ[HHb] increase only in controls. To conclude, the greater prefrontal right-side increases in cerebral %Δ[HHb] and %Δ[tHb] may reflect disturbance of the tooth clenching-related cerebral (de)oxygenation based on impaired reactivity and abnormal microcirculation processes in migraineurs. This finding may have an impact in migraine pathophysiology and help to explain the deleterious effect of masticatory dysfunctions in migraine patients. However, the role of tooth clenching as a migraine trigger calls for further studies.

One-year unsupervised individualized exercise training intervention enhances cardiorespiratory fitness but not muscle deoxygenation or glycemic control in adults with type 1 diabetes.

Adaptations to long-term exercise training in type 1 diabetes are sparsely studied. We examined the effects of a 1-year individualized training intervention on cardiorespiratory fitness, exercise-induced active muscle deoxygenation, and glycemic control in adults with and without type 1 diabetes. Eight men with type 1 diabetes (T1D) and 8 healthy men (CON) matched for age, anthropometry, and peak pulmonary O2 uptake, completed a 1-year individualized training intervention in an unsupervised real-world setting. Before and after the intervention, the subjects performed a maximal incremental cycling test, during which alveolar gas exchange (volume turbine and mass spectrometry) and relative concentration changes in active leg muscle deoxygenated (Δ[HHb]) and total (Δ[tHb]) hemoglobin (near-infrared spectroscopy) were monitored. Peak O2 pulse, reflecting peak stroke volume, was calculated (peak pulmonary O2 uptake/peak heart rate). Glycemic control (glycosylated hemoglobin A1c (HbA1c)) was evaluated. Both T1D and CON averagely performed 1 resistance-training and 3-4 endurance-training sessions per week (∼1 h/session at ∼moderate intensity). Training increased peak pulmonary O2 uptake in T1D (p = 0.004) and CON (p = 0.045) (group × time p = 0.677). Peak O2 pulse also rose in T1D (p = 0.032) and CON (p = 0.018) (group × time p = 0.880). Training increased leg Δ[HHb] at peak exercise in CON (p = 0.039) but not in T1D (group × time p = 0.052), while no changes in leg Δ[tHb] at any work rate were observed in either group (p > 0.05). HbA1c retained unchanged in T1D (from 58 ± 10 to 59 ± 11 mmol/mol, p = 0.609). In conclusion, 1-year adherence to exercise training enhanced cardiorespiratory fitness similarly in T1D and CON but had no effect on active muscle deoxygenation or glycemic control in T1D.

Altered cardiorespiratory response to exercise in overweight and obese women with polycystic ovary syndrome.

In polycystic ovary syndrome (PCOS), cardiovascular risk is increased. Peak O2 uptake (V˙O2peak) predicts the cardiovascular risk. We were the first to examine the contribution of systemic O2 delivery and arteriovenous O2 difference to V˙O2peak in overweight and obese women with PCOS. Fifteen overweight or obese PCOS women and 15 age-, anthropometry-, and physical activity-matched control women performed a maximal incremental cycling exercise test. Alveolar gas exchange (volume turbine and mass spectrometry), arterial O2 saturation (pulse oximetry), and cardiac output (CO) (impedance cardiography) were monitored. Hb concentration was determined. Arterial O2 content and arteriovenous O2 difference (C(a-v)O2) (Fick equation) were calculated. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR). PCOS women had lower V˙O2peak than controls (40 ± 6 vs. 46 ± 5 mL/min/kg fat-free mass [FFM], P = 0.011). Arterial O2 content was similarly maintained in the groups throughout the exercise test (P > 0.05). Linear regression analysis revealed a pronounced response of CO to increasing V˙O2 in PCOS women during the exercise test: A ∆CO/∆V˙O2 slope was steeper in PCOS women than in controls (ß = 5.84 vs. ß = 5.21, P = 0.004). Eventually, the groups attained similar peak CO and peak CO scaled to FFM (P > 0.05). Instead, C(a-v)O2 at peak exercise was lower in PCOS women than in controls (13.2 ± 1.6 vs. 14.8 ± 2.4 mL O2/100 mL blood, P = 0.044). HOMA-IR was similar in the groups (P > 0.05). The altered cardiorespiratory responses to exercise in overweight and obese PCOS women indicate that PCOS per se is associated with alterations in peripheral adjustments to exercise rather than with limitations of systemic O2 delivery.

Central and peripheral cardiovascular impairments limit VO(2peak) in type 1 diabetes.

PURPOSE: Cardiovascular risk, predicted by peak O2 uptake (VO(2peak)), is increased in type 1 diabetes. We examined the contribution of central and peripheral mechanisms to VO(2peak) in physically active adults with type 1 diabetes. METHODS: Seven men with type 1 diabetes and 10 healthy age-, anthropometry-, and physical activity-matched men performed incremental cycling exercise until volitional fatigue. Alveolar gas exchange (turbine and mass spectrometry), cardiac function and systemic vascular resistance (impedance cardiography), and local active leg muscle deoxygenation and blood flow (near infrared spectroscopy) were monitored. Arterial-venous O2 difference was calculated (Fick principle). Blood volume (BV) (carbon monoxide rebreathing method) and glycemic control (glycosylated hemoglobin) were determined. RESULTS: The group with diabetes had lower VO(2peak) than controls (47 ± 5 vs 56 ± 7 mL·min·kg fat-free mass, P < 0.05). At peak exercise, fat-free mass-adjusted stroke volume (SV) and cardiac output (CO) were lower and systemic vascular resistance was higher in the group with diabetes than those in controls (P < 0.05). Leg muscle blood flow was reduced independently of CO in the group with diabetes at peak exercise (P < 0.05), whereas arterial-venous O2 difference was similar in the groups throughout the exercise (P > 0.05). The group with diabetes had lower relative BV than controls (P < 0.01), and BV correlated positively with peak SV and peak CO (P < 0.001). In the group with diabetes, peak SV and peak CO correlated (P < 0.05) and peak leg muscle blood flow tended to correlate (P = 0.070) inversely with glycosylated hemoglobin. CONCLUSIONS: Both central and peripheral cardiovascular impairments limit VO(2peak) in physically active adults with type 1 diabetes. Importantly, central limitations, and probably peripheral limitations as well, are associated with glycemic control.

Alveolar gas exchange, oxygen delivery and tissue deoxygenation in men and women during incremental exercise.

We investigated whether leg and arm skeletal muscle, and cerebral deoxygenation, differ during incremental cycling exercise in men and women, and if women's lower capacity to deliver O2 affects tissue deoxygenation. Men (n=10) compared to women (n=10), had greater cardiac output, which with greater hemoglobin concentration produced greater absolute (QaO2) and body size-adjusted oxygen delivery (QaO2i) at peak exercise. Despite women's lower peak QaO2, their leg muscle deoxygenation was similar at a given work rate and QaO2, but less than in men at peak exercise (Δtissue saturation index -27.1 ± 13.2% vs. -11.8 ± 5.7%, P<0.01; Δ[deoxyhemoglobin] 15.03 ± 8.57 µM vs. 3.73 ± 3.98 µM, P<0.001). At peak exercise, oxygen uptake was associated both with QaO2 and leg muscle deoxygenation (both P<0.01). Arm muscle and cerebral deoxygenation did not differ between sexes at peak exercise. Thus, both high O2 delivery and severe active muscle deoxygenation are determinants of good exercise performance, and active muscle deoxygenation responses are regulated partly in a sex-specific manner with an influence of exercise capacity.

Alveolar gas exchange and tissue oxygenation during incremental treadmill exercise, and their associations with blood O(2) carrying capacity.

The magnitude and timing of oxygenation responses in highly active leg muscle, less active arm muscle, and cerebral tissue, have not been studied with simultaneous alveolar gas exchange measurement during incremental treadmill exercise. Nor is it known, if blood O(2) carrying capacity affects the tissue-specific oxygenation responses. Thus, we investigated alveolar gas exchange and tissue (m. vastus lateralis, m. biceps brachii, cerebral cortex) oxygenation during incremental treadmill exercise until volitional fatigue, and their associations with blood O(2) carrying capacity in 22 healthy men. Alveolar gas exchange was measured, and near-infrared spectroscopy (NIRS) was used to monitor relative concentration changes in oxy- (Δ[O(2)Hb]), deoxy- (Δ[HHb]) and total hemoglobin (Δ[tHb]), and tissue saturation index (TSI). NIRS inflection points (NIP), reflecting changes in tissue-specific oxygenation, were determined and their coincidence with ventilatory thresholds [anaerobic threshold (AT), respiratory compensation point (RC); V-slope method] was examined. Blood O(2) carrying capacity [total hemoglobin mass (tHb-mass)] was determined with the CO-rebreathing method. In all tissues, NIPs coincided with AT, whereas RC was followed by NIPs. High tHb-mass associated with leg muscle deoxygenation at peak exercise (e.g., Δ[HHb] from baseline walking to peak exercise vs. tHb-mass: r = 0.64, p < 0.01), but not with arm muscle- or cerebral deoxygenation. In conclusion, regional tissue oxygenation was characterized by inflection points, and tissue oxygenation in relation to alveolar gas exchange during incremental treadmill exercise resembled previous findings made during incremental cycling. It was also found out, that O(2) delivery to less active m. biceps brachii may be limited by an accelerated increase in ventilation at high running intensities. In addition, high capacity for blood O(2) carrying was associated with a high level of m. vastus lateralis deoxygenation at peak exercise.