Arterial-venous Oxygen Difference Research Articles

Mechanisms of adaptations in cardiorespiratory fitness with exercise prescriptions differing in volume and intensity in middle-age men

Background: To examine the mechanisms of adaptations in cardiorespiratory fitness with different dose of amount and intensity exercise training in middle-aged men. Methods: A total of 67 sedentary subjects aged 40-49 yr were assigned to participate for 12 weeks in a control group or in one of three exercise groups: 1) low volume/moderate intensity 2) low volume/vigorous intensity and 3) high volume/vigorous intensity. They were tested for VO2max, cardiac output (Q) and stroke volume (SV) before and after training and maximal arterial-venous oxygen difference (a-vO2diff) calculated by the Fick Equation. Results: Contrasted to control group, VO2max increased similar in both LVVI and HVVI groups after 12 weeks; It indicated that the intensity of exercise appears to make a greater benefit than the amount of exercise on VO2max. However, Maximal cardiac output (Qmax) and a-vO2diff contributed to increase VO2max were differences in both of vigorous intensity groups. In LVVI group, Qmax together with maximal a-vO2diff contributed to the greater VO2max; in HVVI group, the majority of the increment in VO2max was relied on larger Qmax whereas a widened a-vO2diff. Conclusion: It is appropriate to recommend vigorous intensity exercise to improve cardiorespiratory fitness and encourage higher amount to confer additional benefit for Qmax.

Changes of Entropy Index and Cerebral Oxygen Metabolism in the Maintenance of Remifentanil Anesthesia and Their Predictive Value for Postoperative Hyperalgesia.

Objective To explore the changes of entropy index and cerebral oxygen metabolism in the maintenance of remifentanil anesthesia and the predictive value of postoperative hyperalgesia. Methods A total of 266 patients undergoing general anesthesia in our hospital from January 2020 to October 2021 were selected, and remifentanil was used to maintain anesthesia. The state entropy, reaction entropy, and cerebral oxygen metabolism indexes (cerebral oxygen uptake rate (CERO2), arterial-venous blood oxygen difference (Da-jvO2)) of patients before induction of anesthesia, 15 minutes during the operation, and at the end of the operation were compared. The influencing factors of postoperative hyperalgesia were analyzed. The logistic regression model of postoperative hyperalgesia was established, and the value of entropy index and cerebral oxygen metabolism in predicting postoperative hyperalgesia was evaluated by drawing the receiver operating characteristic curve (ROC). Results The state entropy, response entropy, and CERO2 at 30 min during the operation and at the end of the operation were lower than those before the induction of anesthesia, and Da-jvO2 was higher than that before the induction of anesthesia (P < 0.001). At the end of the operation, the state entropy, reaction entropy, and CERO2 were higher than 30 minutes during the operation, and Da-jvO2 was lower than 30 minutes during the operation (P < 0.001). The dosage of remifentanil, reaction entropy, and CERO2 at the end of the operation entered the logistic model. The AUC value of the reaction entropy and CERO2 combined to predict postoperative hyperalgesia at the end of the operation was 0.851 greater than the reaction entropy at the end of the operation (χ2 = 3.847, P = 0.036), CERO2 (χ2 = 2.589, P = 0.010) single index predictive value. Conclusion The entropy index and cerebral oxygen metabolism in general anesthesia patients change with the progress and discontinuation of remifentanil maintenance anesthesia, and the combination of the two has a high predictive power in postoperative hyperalgesia risk assessment. When the reaction entropy > 54.23, CERO2 > 34.14%, or the total dosage of remifentanil ≥ 30 μg/kg at the end of the operation, we should be highly vigilant of the occurrence of postoperative hyperalgesia and postoperative analgesia management should be strengthened.

Use of the SpO2/FiO2 Diagram to Assess Gas Exchange in Horses Under General Anaesthesia

The aim of this study was to evaluate the validity of the SpO2/FiO2 diagram in estimating gas exchange in horses under general anaesthesia. In this prospective, controlled clinical study were included 10 horses under general anaesthesia. FiO2 was progressively reduced with the following steps: 0.6, 0.4, 0.3 and 0.21; SpO2 was recorded at each step. An arterial blood sample was collected at the steps of 1.0 and 0.21, to calculate intrapulmonary shunt with the Fshunt formula. The Fshunt value calculated at 0.21 FiO2 was defined as “Fshunt 0.21”, the one calculated at 1.0 FiO2 as “Fshunt 1.0”. The FiO2 vs SpO2 data points were analyzed using a computer algorithm which uses the haemoglobin and a fixed value for arterial–venous oxygen difference of 3.5 mL/dL. The algorithm estimates a shunt value fitting the obtained data with an ideal SpO2/FiO2 curve. The value of shunt (Sshunt) was considered for the study. Correlation between “Fshunt 1.0”, “Fshunt0.21” and SShunt was determined using the Spearman Rank Correlation Coefficient test, the analysis of the regression curve and the coefficient of determination (r2). Values of P < .05 were considered statistically significant. A significant and strong correlation (P = .0069; r = 0.839; r2=0.6194) and a significant and moderate correlation (P = .0443; r = 0.644; r2=0.2336) was found between Sshunt and “Fshunt 1.0” and between Sshunt and “Fshunt 0.21”, respectively. The SpO2/FiO2 diagram proved to be a useful and non-invasive tool to characterize gas exchange in horses under general anaesthesia and mechanical ventilation.

Positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome: the heterogeneous effects

BackgroundWe hypothesized that as CARDS may present different pathophysiological features than classic ARDS, the application of high levels of end-expiratory pressure is questionable. Our first aim was to investigate the effects of 5–15 cmH2O of PEEP on partitioned respiratory mechanics, gas exchange and dead space; secondly, we investigated whether respiratory system compliance and severity of hypoxemia could affect the response to PEEP on partitioned respiratory mechanics, gas exchange and dead space, dividing the population according to the median value of respiratory system compliance and oxygenation. Thirdly, we explored the effects of an additional PEEP selected according to the Empirical PEEP-FiO2 table of the EPVent-2 study on partitioned respiratory mechanics and gas exchange in a subgroup of patients.MethodsSixty-one paralyzed mechanically ventilated patients with a confirmed diagnosis of SARS-CoV-2 were enrolled (age 60 [54–67] years, PaO2/FiO2 113 [79–158] mmHg and PEEP 10 [10–10] cmH2O). Keeping constant tidal volume, respiratory rate and oxygen fraction, two PEEP levels (5 and 15 cmH2O) were selected. In a subgroup of patients an additional PEEP level was applied according to an Empirical PEEP-FiO2 table (empirical PEEP). At each PEEP level gas exchange, partitioned lung mechanics and hemodynamic were collected.ResultsAt 15 cmH2O of PEEP the lung elastance, lung stress and mechanical power were higher compared to 5 cmH2O. The PaO2/FiO2, arterial carbon dioxide and ventilatory ratio increased at 15 cmH2O of PEEP. The arterial–venous oxygen difference and central venous saturation were higher at 15 cmH2O of PEEP. Both the mechanics and gas exchange variables significantly increased although with high heterogeneity. By increasing the PEEP from 5 to 15 cmH2O, the changes in partitioned respiratory mechanics and mechanical power were not related to hypoxemia or respiratory compliance. The empirical PEEP was 18 ± 1 cmH2O. The empirical PEEP significantly increased the PaO2/FiO2 but also driving pressure, lung elastance, lung stress and mechanical power compared to 15 cmH2O of PEEP.ConclusionsIn COVID-19 ARDS during the early phase the effects of raising PEEP are highly variable and cannot easily be predicted by respiratory system characteristics, because of the heterogeneity of the disease.

Isolated Knee Extensor Exercise Training Improves Skeletal Muscle Vasodilation, Blood Flow and Functional Capacity in HFpEF Patients

Background Patients with HFpEFexperience severe exercise intolerance due in part to impaired skeletal muscle vascular function during exercise. Whole body exercise interventions yield only modest improvements in cardiac function and functional capacity, and are often not well-tolerated due to severe dyspnea. Therefore, training interventions that isolate smaller muscle groups to improve vascular function may be effective at improving exercise capacity in HFpEF patients while minimizing shortness of breath. Hypothesis Eight weeks of isolated knee extension (KE) exercise training will improve leg blood flow and increase exercise capacity in patients with HFpEF. Methods Nine HFpEF patients (66±5 years, 6 females) performed graded KE exercise (5, 10, and 15W) and maximal aerobic exercise testing (cycle ergometer) before and after 8 weeks of isolated KE training (3x per week, 30 min per leg). Vascular function was assessed by measuring skeletal muscle blood flow (femoral artery ultrasound), mean arterial pressure (ECG-gated sphygmomanometer), and femoral vascular conductance (FVC; index of vasodilation) during graded KE exercise. Functional capacity, quantified as peak pulmonary oxygen uptake (V̇O2, Douglas bags), peak cardiac output (Qc, acetylene rebreathing) and arterial-venous oxygen difference (a-v O2 diff) were measured during a graded maximal cycle exercise to assess cardiac and peripheral adaptations to isolated KE training. Results Eight weeks of isolated KE training lowered blood pressure (Δ: pre: 22±13, post: 12±10.1 mmHg; P=0.02) and improved blood flow (Δ: pre: 950±332, post: 1263±355 ml/min; P=0.02) during 15W isolated KE exercise. The increase in blood flow was due to improved skeletal muscle vasodilation (ΔFVC: pre: 810±417, post: 1234±347 ml/min/100mmHg; P=0.01). During maximal exercise testing, KE training had a small but variable effect on peak Qc (pre: 12.5±3.7, post: 13.2±3.9 l/min; P=0.19), and peripheral oxygen extraction (a-v O2 diff: pre: 10.6±1.8, post: 11.0±1.7 ml/100ml; P=0.17), but resulted in a 13% improvement in peak V̇O2 (pre:12.5±5.5, post: 14.0±6.0; P=0.01). Conclusions Eight weeks of isolated KE training improved skeletal muscle vascular function and blood flow delivery during KE exercise, resulting in improved functional capacity in patients with HFpEF. Exercise interventions aimed at increasing skeletal muscle and vascular function may be effective therapeutic options for HFpEF patients that experience severe dyspnea during whole body exercise.

Factors contributing to exercise capacity in chronic thromboembolic pulmonary hypertension with near-normal hemodynamics

Despite improved survival for patients with chronic thromboembolic pulmonary hypertension (CTEPH) due to progressive medical and interventional treatment, impaired exercise capacity remains common due to poorly understood mechanisms. We aimed to clarify the exercise capacity of CTEPH patients with near-normal pulmonary hemodynamics and evaluate its determinants among the hemodynamic, peripheral (e.g., oxygen use by the peripheral tissues), and muscular (e.g., skeletal muscle strength) factors. Three hundred and twenty-nine patients with CTEPH (mean age, 63 ± 12 years; men/women, 73/256) with a near-normal mean pulmonary artery pressure (≤30 mm Hg) at rest were enrolled. We assessed exercise capacity by peak oxygen consumption (peak VO2) using cardiopulmonary exercise testing with a right heart catheter. We also measured the 6-minute walk distance (6MWD) and quadriceps muscle strength. The mean pulmonary artery pressure was 19 ± 4 mmHg and mean cardiac output was 4.8 ± 1.5 L/min at rest. The mean 6MWD was 444 ± 101 m, while the mean peak VO2 was 14.4 ± 3.9 mL/min/kg. A multivariate model that predicted 6MWD included quadriceps strength (β = 0.45, p < 0.001) and peak arterial venous oxygen difference (β = 0.29, p < 0.001). In contrast, the peak VO2 was best correlated with mPAP-CO slope (β = -0.30, p < 0.001), followed by quadriceps strength and peak arterial venous oxygen difference. The 6MWD performance may be significantly influenced by peripheral oxygen use and muscular factors, while peak VO2 is influenced by hemodynamic and peripheral factors in CTEPH patients with near-normal hemodynamics.

Cardiorespiratory mechanisms underlying the impaired oxygen uptake kinetics at exercise onset after stroke.

Oxygen uptake (V˙O2) kinetics at the onset of exercise is slower in patients with stroke than in healthy adults. However, little is known about the cardiorespiratory mechanisms underlying the impaired V˙O2 kinetics. This study aimed to investigate the relative effect of impaired oxygen delivery and utilisation on V˙O2 kinetics at the onset of submaximal exercise in patients with stroke by comparing the time constants of cardiac output (τCO) and V˙O2 (τV˙O2). In addition, we aimed to examine the association between the kinetics of cardiorespiratory variables and functional outcomes. We included 21 patients with stroke (15 males, mean [SD] age 58.7 [9.5] years, mean days post-stroke 67.9 [30.9]). A submaximal constant-load exercise test was performed to measure τV˙O2, τCO, and the time constant of arterialvenous oxygen difference (τAVO2diff). The ratio of τCO to τV˙O2 was calculated to assess the matching of oxygen delivery and consumption. Fugl-Meyer lower-extremity motor scores, comfortable gait speeds, and Functional Independence Measure motor scores were used as functional variables. Mean (SD) τAVO2diff was markedly shorter than τV˙O2 and τCO (26.1 [7.1] vs. 38.7 [10.2] and 46.6 [23.2 s], P<0.05), with no significant difference between τV˙O2 and τCO (P=0.444). The greater ratio of τCO to τV˙O2 was related to poorer motor function (rho=-0.484, P=0.026) and slower comfortable gait speed (r=-0.482, P=0.027). An increase in CO was slower than that in AVO2diff in patients with stroke. Therefore, V˙O2 kinetics in patients with stroke appears to be affected by a delayed increase in CO rather than AVO2diff. Furthermore, these patients with motor and gait impairments may have a poor matching of oxygen delivery and consumption during exercise onset.

Effects of an allosteric hemoglobin affinity modulator on arterial blood gases and cardiopulmonary responses during normoxic and hypoxic low-intensity exercise.

Numerous pathophysiological conditions induce hypoxemia-related cardiopulmonary perturbations, decrements in exercise capacity, and debilitating symptoms. Accordingly, this study investigated the efficacy of an allosteric hemoglobin modulator (voxelotor) to enhance arterial oxygen saturation during low-intensity exercise in hypoxia. Eight normal healthy subjects (36 ± 7 yr; 73.8 ± 9.5 kg; 3 women) completed a submaximal cycling test (60 W) under normoxic ([Formula: see text]: 0.21; O2 partial pressure: 144 mmHg) and hypoxic ([Formula: see text]: 0.125; O2 partial pressure: 82 mmHg) conditions before (day 1) and after (day 15) 14 days of oral drug administration. While stationary on a cycle ergometer and during exercise, ratings of perceived exertion (RPE) and dyspnea, oxygen consumption (V̇o2), and cardiac output (Q) were measured noninvasively, while arterial blood pressure (MAP) and blood gases ([Formula: see text], [Formula: see text], and [Formula: see text]) were measured invasively. The 14-day drug administration left shifted the oxygen-hemoglobin dissociation curve (ODC; p50 measured at standard pH and Pco2; day 1: 28.0 ± 2.1 mmHg vs. day 15: 26.1 ± 1.8 mmHg, P < 0.05). RPE, dyspnea, V̇o2, Q, and MAP were not different between day 1 and day 15. [Formula: see text] was similar during normoxia on day 1 and day 15 while stationary but higher during exercise (day 1: 95.2 ± 0.4% vs. day 15: 96.6 ± 0.3%, P < 0.05). [Formula: see text] was higher during hypoxia on day 15 while stationary (day 1: 82.9 ± 3.4% vs. day 15: 90.9 ± 1.8%, P < 0.05) and during exercise (day 1: 73.6 ± 2.5% vs. day 15: 84.8 ± 2.7%, P < 0.01). [Formula: see text] and [Formula: see text]were systematically higher and lower, respectively, after drug (P < 0.01), while the alveolar-arterial oxygen difference was unchanged suggesting hyperventilation contributed to the rise in [Formula: see text]. Oral administration of voxelotor left shifted the ODC and stimulated a mild hyperventilation, leading to improved arterial oxygen saturation without altering V̇o2 and central hemodynamics during rest and low-intensity exercise. This effect was more pronounced during submaximal hypoxic exercise, when arterial desaturation was more evident. Additional studies are needed to determine the effects of voxelotor during maximal exercise and under chronic forms of hypoxia.NEW & NOTEWORTHY In humans, a novel allosteric hemoglobin-oxygen affinity modulator was administered to comprehensively examine the cardiopulmonary consequences of stabilizing a portion of the available hemoglobin in a high-oxygen affinity state during submaximal exercise in normoxia and hypoxia. Oral administration of voxelotor enhanced arterial oxygen saturation during submaximal exercise without altering oxygen consumption and central hemodynamics; however, the partial pressure of arterial carbon dioxide was reduced and the partial pressure of arterial oxygen was increased implying that hyperventilation also contributed to the increase in oxygen saturation. The preservation of arterial oxygen saturation and content was particularly evident during hypoxic submaximal exercise, when arterial desaturation typically occurs, but this did not influence arterial-venous oxygen difference.

Using arterial-venous oxygen difference to guide red blood cell transfusion strategy

BackgroundGuidelines recommend a restrictive red blood cell transfusion strategy based on hemoglobin (Hb) concentrations in critically ill patients. We hypothesized that the arterial-venous oxygen difference (A-V O2diff), a surrogate for the oxygen delivery to consumption ratio, could provide a more personalized approach to identify patients who may benefit from transfusion.MethodsA prospective observational study including 177 non-bleeding adult patients with a Hb concentration of 7.0–10.0 g/dL within 72 h after ICU admission. The A-V O2diff, central venous oxygen saturation (ScvO2), and oxygen extraction ratio (O2ER) were noted when a patient’s Hb was first within this range. Transfusion decisions were made by the treating physician according to institutional policy. We used the median A-V O2diff value in the study cohort (3.7 mL) to classify the transfusion strategy in each patient as “appropriate” (patient transfused when the A-V O2diff > 3.7 mL or not transfused when the A-V O2diff ≤ 3.7 mL) or “inappropriate” (patient transfused when the A-V O2diff ≤ 3.7 mL or not transfused when the A-V O2diff > 3.7 mL). The primary outcome was 90-day mortality.ResultsPatients managed with an “appropriate” strategy had lower mortality rates (23/96 [24%] vs. 36/81 [44%]; p = 0.004), and an “appropriate” strategy was independently associated with reduced mortality (hazard ratio [HR] 0.51 [95% CI 0.30–0.89], p = 0.01). There was a trend to less acute kidney injury with the “appropriate” than with the “inappropriate” strategy (13% vs. 26%, p = 0.06), and the Sequential Organ Failure Assessment (SOFA) score decreased more rapidly (p = 0.01). The A-V O2diff, but not the ScvO2, predicted 90-day mortality in transfused (AUROC = 0.656) and non-transfused (AUROC = 0.630) patients with moderate accuracy. Using the ROC curve analysis, the best A-V O2diff cutoffs for predicting mortality were 3.6 mL in transfused and 3.5 mL in non-transfused patients.ConclusionsIn anemic, non-bleeding critically ill patients, transfusion may be associated with lower 90-day mortality and morbidity in patients with higher A-V O2diff.Trial registrationClinicalTrials.gov, NCT03767127. Retrospectively registered on 6 December 2018.

Hemodynamic Response to Exercise in Patients Supported by Continuous Flow Left Ventricular Assist Devices

ObjectivesThis study sought to characterize the hemodynamic response to exercise in LVAD-supported patients and identify parameters most strongly associated with peak oxygen consumption (VO2). BackgroundDespite improved survival for heart failure patients afforded by continuous flow left ventricular assist devices (LVADs), peak exercise capacity remains impaired. Mechanisms underlying this reduced functional capacity remain poorly understood. MethodsPatients referred for post-VAD hemodynamic optimization from December 2017 through June 2019 were enrolled. Swan Ganz catheters were inserted and upright incremental bicycle ergometry with respiratory gas analysis was performed. Hemodynamic measurements, mixed venous saturation, and arterial blood pressure were recorded every 3 min during exercise. Linear correlations were performed between peak VO2 (ml/min) and peak Fick cardiac output (CO), peak device flow, the assumed intrinsic CO derived as Fick CO-device flow, peak pressure differential across the LVAD (mean arterial pressure−pulmonary capillary wedge pressure), peak pressure differential across right ventricle (mean pulmonary artery pressure − right atrial pressure) and systemic vascular resistance. ResultsForty-five patients supported by axial flow pumps (n = 12) and centrifugal flow pumps (n = 33) were studied. There were 34 men and 11 women. Age averaged 60 ± 10 years. Peak VO2 averaged 10.6 ± 3.1 ml/kg/min. Fick CO had the greatest correlation with peak VO2 with r = 0.73 (p < 0.0001) followed by intrinsic CO (r = 0.67; p < 0.0001). Multivariate model that best predicted peak VO2 included Fick CO and peak arterial venous oxygen (AVO2) difference. ConclusionsLVAD supported patients have severely impaired peak exercise capacity. The peak Fick cardiac output was the best correlate of peak exercise performance.

Looking Beyond A-vo2 Difference: Peripheral Adaptations And Vo2Max In Trained And Untrained Adults

PURPOSE: Observing little-to-no increase in arterial-venous oxygen difference (a-vO2diff) following endurance training, some previous investigations have attributed little importance to factors peripheral to the heart, such as maximal mitochondrial oxygen consumption (MitoVO2max) and convective (QmO2) and diffusive (DmO2) muscle oxygen delivery in the training-induced increase in VO2max. As lack of change in a-vO2diff does not necessarily indicate a lack of change in peripheral function, the purpose of this study was to determine the combined influences of adaptations peripheral to the heart in the endurance-training-associated increase in VO2max. METHODS: Arterial-venous blood draws and Doppler ultrasound during maximal single leg knee extension (KE) exercise were used to quantify QmO2, DmO2, a-vO2diff and KEVO2max when free of upstream limitations from the heart in 10 untrained and 10 trained young males. Mitochondrial respiration of muscle biopsied from the vastus lateralis was used to quantify MitoVO2max when free from upstream oxygen supply limitations. RESULTS: In agreement with previous investigations, QmO2 and KEVO2max were 20-35% greater in the trained (P<0.05), while a-vO2diff was not markedly different (P>0.05, See Figures A-C). Nevertheless, training was associated with a 50-100% increases in DmO2 and MitoVO2max, (P<0.05). When plotted as a Wagner diagram (Figure D), it becomes clear that the greater KEVO2max in the trained is the result of 3 synergistic adaptations (1. increased MitoVO2max, 2. increased QmO2 and 3. enhanced DmO2), which, together, raise VO2max more than each adaptation would alone. CONCLUSIONS: Despite minimal changes in a-vO2diff, the training-associated increase in KEVO2max is dependent upon specific peripheral factors within the muscle exhibiting a greater capacity, including mitochondrial respiratory capacity, as well as convective and diffusive muscle oxygen delivery.

Submaximal Exercise Responses Before and During Long Duration Space Flight

PURPOSE: To document the cardiopulmonary responses to submaximal exercise during long-duration International Space Station (ISS) missions. METHODS: Astronauts (n=14) assigned to ISS missions (range: 91-192 d) performed cycle exercise testing ~90 d before launch, ~15 d after launch and every ~30 d thereafter. Peak oxygen consumption (VO2pk) data were previously reported (Moore, et al, 2014). Heart rate (HR, ECG), and oxygen consumption (VO2, Portable Pulmonary Function System, DAC, Denmark) were measured at rest and during 5-min work rates prescribed to elicit 25, 50, and 75% of preflight VO2pk. Cardiac output (Q, Freon 22/SF6 technique) was measured at rest and the 25 and 50% stages. Stroke volume (SV) and arterial-venous oxygen difference (a-v O2d) were calculated. Inflight outcomes were compared to preflight values using mixed-model linear regression with preflight body weight as a covariate. To account for multiplicity, significance thresholds for P values were adjusted (Hochberg procedure). No time trend during flight was evident, thus inflight data are reported as a single outcome. RESULTS: During spaceflight, neither resting VO2 (Pre: 0.41 ± 0.12, In: 0.33 ± 0.07 L/min; Mean ± SD) nor HR (Pre: 71 ± 10, In: 69 ± 11 bpm) differed from preflight, but resting Q (Pre: 5.8 ± 0.9; In: 7.6 ± 0.9 L/min) and SV (Pre: 83 ± 19, In: 112 ± 21 ml/beat) were higher while resting a-v O2d was lower (Pre: 7.0 ± 2.0, In: 4.4 ± 0.8 ml O2/100 mL). During exercise, VO2 was lower at the 25% stage during flight (Pre: 0.95 ± 0.19, In: 0.81 ± 0.14 L/min), but did not differ from preflight during any other exercise stage. Inflight HR did not differ from preflight in the 25% stage (Pre: 88 ± 11, In: 89 ± 14 bpm), but HR was elevated during the 50% stage (Pre: 113 ± 15, In: 122 ± 16 bpm) and the 75% stage (Pre: 147 ± 16, In: 158 ± 16 bpm). In contrast to rest, exercise Q and SV did not differ from pre- to inflight, although a-v O2d was reduced during both the 25% stage (Pre: 9.8 ± 0.8, In: 7.7 ± 0.5 ml O2/100 mL) and the 50% stage (Pre: 12.8 ± 0.9, In: 10.2 ± 0.8 ml O2/100 mL). CONCLUSION: Lower VO2 during the 25% stage on ISS may result from reduced metabolic cost of pedal upstroke. Maintained exercise Q and SV during flight suggest central cardiovascular factors did not limit submaximal exercise at these levels. Lower a-v O2d during flight may be related to altered blood flow distribution in space.

Exercise Induces Peripheral Muscle But Not Cardiac Adaptations After Stroke: A Randomized Controlled Pilot Trial

ObjectiveTo explore the physiological factors affecting exercise-induced changes in peak oxygen consumption and function poststroke. DesignSingle-center, single-blind, randomized controlled pilot trial. SettingCommunity stroke services. ParticipantsAdults (N=40; age>50y; independent with/without stick) with stroke (diagnosed >6mo previously) were recruited from 117 eligible participants. Twenty participants were randomized to the intervention group and 20 to the control group. No dropouts or adverse events were reported. InterventionsIntervention group: 19-week (3times/wk) progressive mixed (aerobic/strength/balance/flexibility) community group exercise program. Control group: Matched duration home stretching program. Main Outcome Measures(1) Pre- and postintervention: maximal cardiopulmonary exercise testing with noninvasive (bioreactance) cardiac output measurements; and (2) functional outcome measures: 6-minute walk test; timed Up and Go test, and Berg Balance Scale. ResultsExercise improved peak oxygen consumption (18±5 to 21±5mL/(kg⋅min); P<.01) and peak arterial-venous oxygen difference (9.2±2.7 to 11.4±2.9mL of O2/100mL of blood; P<.01), but did not alter cardiac output (17.2±4 to 17.7±4.2L/min; P=.44) or cardiac power output (4.8±1.3 to 5.0±1.35W; P=.45). A significant relation existed between change in peak oxygen consumption and change in peak arterial-venous oxygen difference (r=.507; P<.05), but not with cardiac output. Change in peak oxygen consumption did not strongly correlate with change in function. ConclusionsExercise induced peripheral muscle, but not cardiac output, adaptations after stroke. Implications for stroke clinical care should be explored further in a broader cohort.

Use of Oxygen Pulse in Predicting Doppler-Derived Maximal Stroke Volume in Adolescents.

Clinical exercise physiologists and physicians administering stress tests in the young have used oxygen pulse as a surrogate measure of stroke volume. It is important to recognize 1) the accuracy of O₂ pulse in predicting maximal stroke volume during exercise, and 2) the normal pattern of O₂ pulse during a progressive exercise test. This study examined both of these issues in a cohort of 44 healthy adolescent males and females (ages 14-16 years) who performed routine progressive cycle exercise to exhaustion. Gas exchange variables were measured by standard open circuit techniques. Stroke volume at rest and during exercise was assessed by the Doppler ultrasound method. At peak exercise O₂ pulse correlated closely with stroke volume (r = .73) with a SEE of 12.6 ml·beat⁻¹. Values of maximal O₂ pulse in nonathletic boys and girls were 13.3 ± 2.5 and 11.0 ± 1.7 ml·beat⁻¹, respectively. After the initial workload, a steady rise was observed in O₂ pulse, entirely reflecting an increasing arterial venous oxygen difference, with a slope of approximately 4 ml/beat per 100 watts work load. The findings support the use of O₂ pulse as a valid predictor of stroke volume during exercise in youth with a moderately high level of accuracy.

The Use of the Ratio between the Veno-arterial Carbon Dioxide Difference and the Arterial-venous Oxygen Difference to Guide Resuscitation in Cardiac Surgery Patients with Hyperlactatemia and Normal Central Venous Oxygen Saturation.

Background:After cardiac surgery, central venous oxygen saturation (ScvO2) and serum lactate concentration are often used to guide resuscitation; however, neither are completely reliable indicators of global tissue hypoxia. This observational study aimed to establish whether the ratio between the veno-arterial carbon dioxide and the arterial-venous oxygen differences (P(v−a)CO2/C(a−v)O2) could predict whether patients would respond to resuscitation by increasing oxygen delivery (DO2).Methods:We selected 72 patients from a cohort of 290 who had undergone cardiac surgery in our institution between January 2012 and August 2014. The selected patients were managed postoperatively on the Intensive Care Unit, had a normal ScvO2, elevated serum lactate concentration, and responded to resuscitation by increasing DO2 by >10%. As a consequence, 48 patients responded with an increase in oxygen consumption (VO2) while VO2 was static or fell in 24.Results:At baseline and before resuscitative intervention in postoperative cardiac surgery patients, a P(v−a)CO2/C(a−v)O2 ratio ≥1.6 mmHg/ml predicted a positive VO2 response to an increase in DO2 of >10% with a sensitivity of 68.8% and a specificity of 87.5%.Conclusions:P(v−a)CO2/C(a−v)O2 ratio appears to be a reliable marker of global anaerobic metabolism and predicts response to DO2 challenge. Thus, patients likely to benefit from resuscitation can be identified promptly, the P(v−a)CO2/C(a−v)O2 ratio may, therefore, be a useful resuscitation target.

PARIS: A good start for exercise in HFPEF.

Heart failure (HF) is a complex clinical syndrome characterized by a constellation of signs and symptoms involving various organ systems. Structural and/or functional cardiac abnormalities form a cornerstone to the pathophysiology of HF. However, extracardiac dysfunction plays an equally important role in its development and progression.1 Approximately 50% or more of HF patients have HF with preserved left ventricular ejection fraction (HFPEF), and the proportion is higher among women and the elderly.2,3 The main symptoms of this entity – similar to HF with reduced ejection fraction (HFREF) – are related to exercise intolerance4–9 (dyspnea and fatigue) as well as reduced quality of life.5 However, the pathophysiology of exercise intolerance in this group of patients is not well understood. There is scarcity in HFPEF mechanistic clinical studies and relatively few data regarding its treatment.10 Exercise intolerance can be objectively expressed by reduced peak exercise oxygen consumption (VO2) measured by expired gas analysis, a technique that is valid and reproducible in patients with HFPEF.11,12 According to Fick's equation, reduced peak VO2 results from either reduced cardiac output (CO), peripheral arterial-venous oxygen difference (A-VO2 Diff), or both. Many studies have reported that endurance exercise training (EET) improves peak VO2 in patients with HFREF,13,14 and that this improvement results from favorable changes in cardiac,13,15–17 peripheral vascular,15 and skeletal muscle function.16,18–20 These changes increase oxygen delivery to, and utilization by, the active muscles (i.e., increased A-VO2 Diff). In contrast, there are only four studies of such kind in patients with HFPEF21–24 and the mechanisms of exercise training effects in this group are not known yet.

Endothelin-A-mediated vasoconstriction during exercise with advancing age.

The endothelin-1 vasoconstrictor pathway contributes to age-related elevations in resting peripheral vascular tone primarily through activation of the endothelin subtype A (ET(A)) receptor. However, the regulatory influence of ET(A)-mediated vasoconstriction during exercise in the elderly is unknown. Thus, in 17 healthy volunteers (n = 8 young, 24±2 years; n = 9 old, 70±2 years), we examined leg blood flow, mean arterial pressure, leg arterial-venous oxygen (O2) difference, and leg O2 consumption (VO2) at rest and during knee-extensor exercise before and after intra-arterial administration of the ET(A) antagonist BQ-123. During exercise, BQ-123 administration increased leg blood flow to a greater degree in the old (+29±5 mL/min/W) compared with the young (+16±3 mL/min/W). The increase in leg blood flow with BQ-123 was accompanied by an increase in leg VO2 in both groups, suggesting a reduced efficiency following ET(A) receptor blockade. Together, these findings have identified an age-related increase in ET(A)-mediated vasoconstrictor activity that persists during exercise, suggesting an important role of this pathway in the regulation of exercising skeletal muscle blood flow and maintenance of arterial blood pressure in the elderly.

Defining cardiac adaptations and safety of endurance training in patients with m.3243A&gt;G-related mitochondrial disease

BackgroundCardiac hypertrophic remodelling and systolic dysfunction are common in patients with mitochondrial disease and independent predictors of morbidity and early mortality. Endurance exercise training improves symptoms and skeletal muscle function, yet cardiac adaptations are unknown.Methods and resultsBefore and after 16-weeks of training, exercise capacity, cardiac magnetic resonance imaging and phosphorus-31 spectroscopy, disease burden, fatigue, quality of life, heart rate variability (HRV) and blood pressure variability (BPV) were assessed in 10 adult patients with m.3243A>G-related mitochondrial disease, and compared to age- and gender-matched sedentary control subjects. At baseline, patients had increased left ventricular mass index (LVMI, p < 0.05) and LV mass to end-diastolic volume ratio, and decreased longitudinal shortening and myocardial phosphocreatine/adenosine triphosphate ratio (all p < 0.01). Peak arterial–venous oxygen difference (p < 0.05), oxygen uptake (VO2) and power were decreased in patients (both p < 0.01) with no significant difference in cardiac power output. All patients remained stable and completed ≥ 80% sessions. With training, there were similar proportional increases in peak VO2, anaerobic threshold and work capacity in patients and controls. LVMI increased in both groups (p < 0.01), with no significant effect on myocardial function or bioenergetics. Pre- and post-exercise training, HRV and BPV demonstrated increased low frequency and decreased high frequency components in patients compared to controls (all p < 0.05).ConclusionPatients with mitochondrial disease and controls achieved similar proportional benefits of exercise training, without evidence of disease progression, or deleterious effects on cardiac function. Reduced exercise capacity is largely mediated through skeletal muscle dysfunction at baseline and sympathetic over-activation may be important in pathogenesis.

Maximal strength training and increased work efficiency: contribution from the trained muscle bed

Maximal strength training (MST) reduces pulmonary oxygen uptake (Vo(2)) at a given submaximal exercise work rate (i.e., efficiency). However, whether the increase in efficiency originates in the trained skeletal muscle, and therefore the impact of this adaptation on muscle blood flow and arterial-venous oxygen difference (a-vO(2diff)), is unknown. Thus five trained subjects partook in an 8-wk MST intervention consisting of half-squats with an emphasis on the rate of force development during the concentric phase of the movement. Pre- and posttraining measurements of pulmonary Vo(2) (indirect calorimetry), single-leg blood flow (thermodilution), and single-leg a-vO(2diff) (blood gases) were performed, to allow the assessment of skeletal muscle Vo(2) during submaximal cycling [237 ± 23 W; ∼60% of their peak pulmonary Vo(2) (Vo(2peak))]. Pulmonary Vo(2peak) (∼4.05 l/min) and peak work rate (∼355 W), assessed during a graded exercise test, were unaffected by MST. As expected, following MST there was a significant reduction in pulmonary Vo(2) during steady-state submaximal cycling (∼237 W: 3.2 ± 0.1 to 2.9 ± 0.1 l/min). This was accompanied by a significant reduction in single-leg Vo(2) (1,101 ± 105 to 935 ± 93 ml/min) and single-leg blood flow (6,670 ± 700 to 5,649 ± 641 ml/min), but no change in single-leg a-vO(2diff) (16.7 ± 0.8 to 16.8 ±0.4 ml/dl). These data confirm an MST-induced reduction in pulmonary Vo(2) during submaximal exercise and identify that this change in efficiency originates solely in skeletal muscle, reducing muscle blood flow, but not altering muscle a-vO(2diff).

Thigh oxygen uptake at the onset of intense exercise is not affected by a reduction in oxygen delivery caused by hypoxia

In response to hypoxic breathing most studies report slower pulmonary oxygen uptake (Vo2) kinetics at the onset of exercise, but it is not known if this relates to an actual slowing of the Vo2 in the active muscles(.) The aim of the present study was to evaluate whether thigh Vo2 is slowed at the onset of intense exercise during acute exposure to hypoxia. Six healthy male subjects (25.8 ± 1.4 yr, 79.8 ± 4.0 kg, means ± SE) performed intense (100 ± 6 watts) two-legged knee-extensor exercise for 2 min in normoxia (NOR) and hypoxia [fractional inspired oxygen concentration (Fi(O2)) = 0.13; HYP]. Thigh Vo2 was measured by frequent arterial and venous blood sampling and blood flow measurements. In arterial blood, oxygen content was reduced (P < 0.05) from 191 ± 5 ml O2/l in NOR to 180 ± 5 ml O2/l in HYP, and oxygen pressure was reduced (P < 0.001) from 111 ± 4 mmHg in NOR to 63 ± 4 mmHg in HYP. Thigh blood flow was the same in NOR and HYP, and thigh oxygen delivery was consequently reduced (P < 0.05) in HYP, but femoral arterial-venous oxygen difference and thigh Vo(2) were similar in NOR and HYP. In addition, muscle lactate release was the same in NOR and HYP, and muscle lactate accumulation during the first 25 s of exercise determined from muscle biopsy sampling was also similar (0.35 ± 0.07 and 0.36 ± 0.07 mmol·kg dry wt(-1)·s(-1) in NOR and HYP). Thus the increase in thigh Vo2 was not attenuated at the onset of intense knee-extensor exercise despite a reduction in oxygen delivery and pressure.