scholarly journals The Vascular Side of Chronic Bed Rest: When a Therapeutic Approach Becomes Deleterious

2020 ◽  
Vol 9 (4) ◽  
pp. 918 ◽  
Author(s):  
Anna Pedrinolla ◽  
Alessandro L. Colosio ◽  
Roberta Magliozzi ◽  
Elisa Danese ◽  
Emine Kirmizi ◽  
...  
Keyword(s):  
Blood Flow ◽  
Shear Rate ◽  
Vascular Function ◽  
Inflammatory Markers ◽  
Near Infrared ◽  
Vastus Lateralis ◽  
Vascular Inflammation ◽  
Bed Rest ◽  
Total Hemoglobin ◽  
No Bioavailability

The interplay between chronic constraint and advanced aging on blood flow, shear-rate, vascular function, nitric oxide (NO)-bioavailability, microcirculation, and vascular inflammation factors is still a matter of debate. Ninety-eight individuals (Young, n = 28, 23 ± 3 yrs; Old, n = 36, 85 ± 7 yrs; Bedridden, n = 34, 88 ± 6 yrs) were included in the study. The bedridden group included old individuals chronically confined to bed (3.8 ± 2.3 yrs). A blood sample was collected and analyzed for plasma nitrate, and vascular inflammatory markers. Hyperemic response (∆peak) during the single passive leg movement (sPLM) test was used to measure vascular function. Skeletal muscle total hemoglobin was measured at the vastus lateralis during the sPLM test, by means of near infrared spectroscopy (NIRS). Bedridden subjects revealed a depletion of plasma nitrates compared with Old (−23.8%) and Young (−31.1%). Blood flow was lower in the Bedridden in comparison to Old (−20.1%) and Young (−31.7%). Bedridden presented lower sPLM ∆peak compared Old (−72.5%) and the Young (−83.3%). ∆peak of NIRS total hemoglobin was lower in the Bedridden compared to that in the Young (−133%). All vascular inflammatory markers except IL-6 were significantly worse in the Bedridden compared to Old and Young. No differences were found between the Old and Young in inflammatory markers. Results of this study confirm that chronic physical constraint induces an exacerbation of vascular disfunction and differential regulation of vascular-related inflammatory markers. The mechanisms involved in these negative adaptations seems to be associated with endothelial dysfunction and consequent diminished NO-bioavailability likely caused by the reduced shear-rate consequential to long-term reduction of physical activity.

scholarly journals Functional impairment of skeletal muscle oxidative metabolism during knee extension exercise after bed rest

2011 ◽  
Vol 111 (6) ◽  
pp. 1719-1726 ◽  
Author(s):  
Desy Salvadego ◽  
Stefano Lazzer ◽  
Mauro Marzorati ◽  
Simone Porcelli ◽  
Enrico Rejc ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Oxidative Metabolism ◽  
Near Infrared ◽  
Vastus Lateralis ◽  
Bed Rest ◽  
Knee Extension ◽  
Functional Evaluation

A functional evaluation of skeletal muscle oxidative metabolism during dynamic knee extension (KE) incremental exercises was carried out following a 35-day bed rest (BR) (Valdoltra 2008 BR campaign). Nine young male volunteers (age: 23.5 ± 2.2 yr; mean ± SD) were evaluated. Pulmonary gas exchange, heart rate and cardiac output (by impedance cardiography), skeletal muscle (vastus lateralis) fractional O2 extraction, and brain (frontal cortex) oxygenation (by near-infrared spectroscopy) were determined during incremental KE. Values at exhaustion were considered “peak”. Peak heart rate (147 ± 18 beats/min before vs. 146 ± 17 beats/min after BR) and peak cardiac output (17.8 ± 3.3 l/min before vs. 16.1 ± 1.8 l/min after BR) were unaffected by BR. As expected, brain oxygenation did not decrease during KE. Peak O2 uptake was lower after vs. before BR, both when expressed as liters per minute (0.99 ± 0.17 vs. 1.26 ± 0.27) and when normalized per unit of quadriceps muscle mass (46.5 ± 6.4 vs. 56.9 ± 11.0 ml·min−1·100 g−1). Skeletal muscle peak fractional O2 extraction, expressed as a percentage of the maximal values obtained during a transient limb ischemia, was lower after (46.3 ± 12.1%) vs. before BR (66.5 ± 11.2%). After elimination, by the adopted exercise protocol, of constraints related to cardiovascular O2 delivery, a decrease in peak O2 uptake and muscle peak capacity of fractional O2 extraction was found after 35 days of BR. These findings suggest a substantial impairment of oxidative function at the muscle level, “downstream” with respect to bulk blood flow to the exercising muscles, that is possibly at the level of blood flow distribution/O2 utilization inside the muscle, peripheral O2 diffusion, and intracellular oxidative metabolism.

Human respiratory muscle blood flow measured by near-infrared spectroscopy and indocyanine green

2008 ◽  
Vol 104 (4) ◽  
pp. 1202-1210 ◽  
Author(s):  
Jordan A. Guenette ◽  
Ioannis Vogiatzis ◽  
Spyros Zakynthinos ◽  
Dimitrios Athanasopoulos ◽  
Maria Koskolou ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Infrared Spectroscopy ◽  
Respiratory Muscle ◽  
Near Infrared ◽  
Vastus Lateralis ◽  
Muscle Blood Flow ◽  
Work Of Breathing ◽  
Dilution Method ◽  
Transdiaphragmatic Pressure

Measurement of respiratory muscle blood flow (RMBF) in humans has important implications for understanding patterns of blood flow distribution during exercise in healthy individuals and those with chronic disease. Previous studies examining RMBF in humans have required invasive methods on anesthetized subjects. To assess RMBF in awake subjects, we applied an indicator-dilution method using near-infrared spectroscopy (NIRS) and the light-absorbing tracer indocyanine green dye (ICG). NIRS optodes were placed on the left seventh intercostal space at the apposition of the costal diaphragm and on an inactive control muscle (vastus lateralis). The primary respiratory muscles within view of the NIRS optodes include the internal and external intercostals. Intravenous bolus injection of ICG allowed for cardiac output (by the conventional dye-dilution method with arterial sampling), RMBF, and vastus lateralis blood flow to be quantified simultaneously. Esophageal and gastric pressures were also measured to calculate the work of breathing and transdiaphragmatic pressure. Measurements were obtained in five conscious humans during both resting breathing and three separate 5-min bouts of constant isocapnic hyperpnea at 27.1 ± 3.2, 56.0 ± 6.1, and 75.9 ± 5.7% of maximum minute ventilation as determined on a previous maximal exercise test. RMBF progressively increased (9.9 ± 0.6, 14.8 ± 2.7, 29.9 ± 5.8, and 50.1 ± 12.5 ml·100 ml−1·min−1, respectively) with increasing levels of ventilation while blood flow to the inactive control muscle remained constant (10.4 ± 1.4, 8.7 ± 0.7, 12.9 ± 1.7, and 12.2 ± 1.8 ml·100 ml−1·min−1, respectively). As ventilation rose, RMBF was closely and significantly correlated with 1) cardiac output ( r = 0.994, P = 0.006), 2) the work of breathing ( r = 0.995, P = 0.005), and 3) transdiaphragmatic pressure ( r = 0.998, P = 0.002). These data suggest that the NIRS-ICG technique provides a feasible and sensitive index of RMBF at different levels of ventilation in humans.

Abstract 032: Uninterrupted Sitting Induces Unfavorable Changes In Resting Hemodynamics And Inflammatory And Vascular Biomarkers In Physically Inactive And Active Adults

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Megan C Nelson ◽  
Madeline P Casanova ◽  
Jennavere R Ball ◽  
Rachel D Midence ◽  
Timothy R Johnson ◽  
...  
Keyword(s):  
Physical Activity ◽  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Shear Rate ◽  
Arterial Pressure ◽  
Vascular Function ◽  
Blood Velocity ◽  
Inflammatory Biomarkers ◽  
Active Adults ◽  
Over Time

Introduction: A single bout of uninterrupted sitting impairs vascular function in the legs, which may be due to reductions in blood flow and shear stress. Participating in regular moderate-to-vigorous physical activity (MVPA) has been identified as an effective approach for improving vascular function, and recent evidence suggests meeting the physical activity (PA) guidelines may attenuate some of the negative health outcomes associated with excessive sedentary behavior; however, it is not well understood how meeting the PA guidelines may influence the acute response to sitting. Our aim was to investigate the effects of 3 h of uninterrupted sitting on hemodynamics and vascular and inflammatory biomarkers in physically inactive and active adults. Hypothesis: We hypothesized active adults would experience less detrimental physiological changes after sitting compared to inactive adults. Methods: Eleven inactive (mean±SD, age: 47.1±8.9 y, body fat: 33.1±8.5%; 78.5% women) and 16 active adults (age: 46.1±8.9 y, body fat: 25.2±7.2%; 31.1% women) completed 3 h of uninterrupted sitting. Adults self-reported their PA with the International PA Questionnaire. Adults engaging in ≥150 min·wk -1 were classified as active and <150 min·wk -1 , inactive. Hemodynamic variables, and superficial femoral artery (SFA) diameter and blood velocity were measured each hour over 3 h of sitting. Mean arterial pressure, blood flow and shear rate were calculated. Serum vascular and inflammatory biomarkers were measured pre and post sitting. Linear mixed-effects modeling was used to assess changes in dependent variables over time and between inactive and active adults, controlling for sex. Results: Inactive and active adults self-reported 7.3±7.1 and 93.3±64.8 min·d -1 of MVPA, respectively. Endothelin-1 (baseline: 8.3±13.4 pg/mL, post: 81.1±103.0 pg/mL; p<0.001) and interleukin-6 (baseline: 0.08±0.06 pg/mL, post: 0.11±0.11 pg/mL; p=0.03) increased post sitting compared to baseline in all adults, regardless of PA status. Systolic blood pressure, mean arterial pressure, calf circumference, and SFA diameter, blood velocity, and mean blood flow decreased over time in both groups (p<0.05 for all). There was an interaction effect for mean shear rate (p=0.008); inactive adults experienced a decline over 3 h of sitting (baseline: 76.1±48.2 s -1 ; 1 h: 55.0±27.4 s -1 ; 2 h: 45.3±24.2 s -1 ; 3 h: 40.8±25.5 s -1 ) while active participants demonstrated no change (baseline: 36.6±21.4 s -1 ; 1 h: 28.1±21.4 s -1 ; 2 h: 26.1±20.9 s -1 ; 3 h: 23.8±19.5 s -1 ). Inactive adults also had a higher oscillatory shear index compared to active adults (p<0.001). Conclusion: Uninterrupted sitting induced unfavorable changes regardless of PA status; however, active adults demonstrated a more favorable shear profile. Meeting PA guidelines may attenuate some unfavorable changes within the vasculature associated with prolonged sitting.

scholarly journals Blood flow occlusion-related O2 extraction “reserve” is present in different muscles of the quadriceps but greater in deeper regions after ramp-incremental test

2018 ◽  
Vol 125 (2) ◽  
pp. 313-319 ◽  
Author(s):  
Danilo Iannetta ◽  
Dai Okushima ◽  
Erin Calaine Inglis ◽  
Narihiko Kondo ◽  
Juan M Murias ◽  
...  
Keyword(s):  
Blood Flow ◽  
Near Infrared ◽  
Vastus Lateralis ◽  
Rectus Femoris ◽  
Incremental Exercise ◽  
Vastus Lateralis Muscle ◽  
Incremental Test ◽  
Time Resolved ◽  
Blood Flow Occlusion ◽  
Flow Occlusion

It was recently demonstrated that an O2 extraction reserve, as assessed by the near-infrared spectroscopy (NIRS)-derived deoxygenation signal ([HHb]), exists in the superficial region of vastus lateralis (VL) muscle during an occlusion performed at the end of a ramp-incremental test. However, it is unknown whether this reserve is present and/or different in magnitude in other portions and depths of the quadriceps muscles. We tested the hypothesis that an O2 extraction reserve would exist in other regions of this muscle but is greater in deep compared with more superficial portions. Superficial (VL-s) and deep VL (VL-d) as well as superficial rectus femoris (RF-s) were monitored by a combination of low- and high-power time-resolved (TRS) NIRS. During the occlusion immediately post-ramp-incremental test there was a significant overshoot in the [HHb] signal ( P < 0.05). However, the magnitude of this increase was greater in VL-d (93.2 ± 42.9%) compared with VL-s (55.0 ± 19.6%) and RF-s (47.8 ± 14.0%) ( P < 0.05). The present study demonstrated that an O2 extraction reserve exists in different pools of active muscle fibers of the quadriceps at the end of a ramp exercise to exhaustion. The greater magnitude in the reserve observed in the deeper portion of VL, however, suggests that this portion of muscle may present a greater surplus of oxygenated blood, which is likely due to a greater population of slow-twitch fibers. These findings add to the notion that the plateau in the [HHb] signal toward the end of a ramp-incremental exercise does not indicate the upper limit of O2 extraction. NEW & NOTEWORTHY Different portions of the quadriceps muscles exhibited an untapped O2 extraction reserve during a blood flow occlusion performed at the end of a ramp-incremental exercise. In the deeper portion of the vastus lateralis muscle, this reserve was greater compared with superficial vastus lateralis and rectus femoris. These data suggest that the O2 extraction reserve may be dependent on the vascular and/or oxidative capacities of the muscles.

scholarly journals Perfusion pressure and movement-induced hyperemia: evidence of limited vascular function and vasodilatory reserve with age

2013 ◽  
Vol 304 (4) ◽  
pp. H610-H619 ◽  
Author(s):  
H. Jonathan Groot ◽  
Joel D. Trinity ◽  
Gwenael Layec ◽  
Matthew J. Rossman ◽  
Stephen J. Ives ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Function ◽  
Perfusion Pressure ◽  
The Elderly ◽  
Passive Movement ◽  
Hemodynamic Responses ◽  
Central Hemodynamic ◽  
Seated Posture ◽  
No Bioavailability ◽  
The Impact

To better understand the mechanisms contributing to reduced blood flow with age, this study sought to elucidate the impact of altered femoral perfusion pressure (FPP) on movement-induced hyperemia. Passive leg movement was performed in 10 young (22 ± 1 yr) and 12 old (72 ± 2 yr) healthy men for 2 min, with and without a posture-induced change in FPP (∼7 ± 1 ΔmmHg). Second-by-second measurements of central and peripheral hemodynamic responses were acquired noninvasively (finger photoplethysmography and Doppler ultrasound, respectively), with FPP confirmed in a subset of four young and four old subjects with arterial and venous catheters. Central hemodynamic responses (heart rate, stroke volume, cardiac output, mean arterial pressure) were not affected by age or position. The young exhibited a ∼70% greater movement-induced peak change in leg blood flow (ΔLBFpeak) in the upright-seated posture (supine: 596±68 ml/min; upright: 1,026 ± 85 ml/min). However, in the old the posture change did not alter ΔLBFpeak (supine: 417±42 ml/min; upright: 412±56 ml/min), despite the similar increases in FPP. Similarly, movement-induced peak change in leg vascular conductance was ∼80% greater for the young in the upright-seated posture (supine: 7.1 ± 0.8 ml·min−1·mmHg−1; upright: 12.8 ± 1.3 ml·min−1·mmHg−1), while the old again exhibited no difference between postures (supine: 4.7 ± 0.4 ml·min−1·mmHg−1; upright: 4.8 ± 0.5 ml·min−1·mmHg−1). Thus this study reveals that, unlike the young, increased FPP does not elicit an increase in movement-induced hyperemia or vasodilation in the old. In light of recent evidence that the majority of the first minute of passive movement-induced hyperemia is predominantly nitric oxide (NO) dependent in the young, these findings in the elderly may be largely due to decreased NO bioavailability, but this remains to be definitively determined.

A method for assessing heterogeneity of blood flow and metabolism in exercising normal human muscle by near-infrared spectroscopy

2015 ◽  
Vol 118 (6) ◽  
pp. 783-793 ◽  
Author(s):  
Ioannis Vogiatzis ◽  
Helmut Habazettl ◽  
Zafeiris Louvaris ◽  
Vasileios Andrianopoulos ◽  
Harrieth Wagner ◽  
...  
Keyword(s):  
Blood Flow ◽  
Infrared Spectroscopy ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
Vastus Lateralis ◽  
Regional Distribution ◽  
Human Muscle ◽  
Relative Dispersion ◽  
Wide Range ◽  
Normal Human

Heterogeneity in the distribution of both blood flow (Q̇) and O2 consumption (V̇o2) has not been assessed by near-infrared spectroscopy in exercising normal human muscle. We used near-infrared spectroscopy to measure the regional distribution of Q̇ and V̇o2 in six trained cyclists at rest and during constant-load exercise (unloaded pedaling, 20%, 50%, and 80% of peak Watts) in both normoxia and hypoxia (inspired O2 fraction = 0.12). Over six optodes over the upper, middle, and lower vastus lateralis, we recorded 1) indocyanine green dye inflow after intravenous injection to measure Q̇; and 2) fractional tissue O2 saturation (StiO2) to estimate local V̇o2-to-Q̇ ratios (V̇o2/Q̇). Varying both exercise intensity and inspired O2 fraction provided a (directly measured) femoral venous O2 saturation range from about 10 to 70%, and a correspondingly wide range in StiO2. Mean Q̇-weighted StiO2 over the six optodes related linearly to femoral venous O2 saturation in each subject. We used this relationship to compute local muscle venous blood O2 saturation from StiO2 recorded at each optode, from which local V̇o2/Q̇ could be calculated by the Fick principle. Multiplying regional V̇o2/Q̇ by Q̇ yielded the corresponding local V̇o2. While six optodes along only in one muscle may not fully capture the extent of heterogeneity, relative dispersion of both Q̇ and V̇o2 was ∼0.4 under all conditions, while that for V̇o2/Q̇ was minimal (only ∼0.1), indicating in fit young subjects 1) a strong capacity to regulate Q̇ according to regional metabolic need; and 2) a likely minimal impact of heterogeneity on muscle O2 availability.

Cerebral Blood Flow and Metabolic Correlates of Near Infrared Spectroscopy in Patients with Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1386-1386
Author(s):  
Adam M Bush ◽  
Matthew Borzage ◽  
Thomas Coates ◽  
John C Wood ◽  
Soyoung Choi
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Infrared Spectroscopy ◽  
Oxygen Delivery ◽  
Oxygen Supply ◽  
Near Infrared ◽  
Cell Disease ◽  
T2 Relaxation ◽  
Total Hemoglobin ◽  
The Relationship

Abstract Introduction Tissue oxygen index (TOI), by near Infrared Spectroscopy (NIRS), is a valuable tool for noninvasive, indirect measurement of oxygen supply-demand balance. Cerebral TOI is decreased in sickle cell disease (SCD), and correlates with disease severity. Previous work suggests that cerebral TOI is inversely correlated with hemoglobin S level and chronic transfusion therapy restores TOI to normal values. Nahavandi et al. have proposed that low cerebral TOI in SCD disease can be attributed to impaired oxygen delivery and/or carrying capacity of sickle blood. Unfortunately, the specificity of cerebral TOI is still an area of active debate. In order to elucidate these mechanisms we measured global cerebral blood flow (CBF),arterial oxygen content (CaO2), oxygen delivery (DO2), arterial and venous oxygen saturation (SaO2 and SvO2) and oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in 12 healthy controls and 15 SCD patients using magnetic resonance imaging (MRI). Methods All patients were recruited with informed consent or assent and this study was approved by the CHLA IRB. Fifteen patients with SCD and 12 healthy ethnicity matched controls (CTL) were studied. MRI compatible NIRS probes were placed on the forehead and TOI was recorded throughout the entire MRI examination. SaO2 was measured via peripheral pulse oximetery. Phase Contrast (PC) of the carotid and vertebral arteries was used to measure global CBF. T2 Relaxation Under Spin Tagging (TRUST) was used to measured T2 relaxation of blood within the sagittal sinus. T2 relaxation was converted to SvO2 via calibration curves. Blood draw for hemoglobin and electrophoresis was performed. Exclusion criteria included pregnancy, previous stroke, acute chest or pain crisis hospitalization within one month. Results Table 1 summarizes the relationship between cerebral TOI, age, laboratory values, and hemodynamic variables. Surprisingly, TOI was independent of indices of oxygen supply (SaO2, CBF, oxygen delivery) and oxygen demand (CMRO2); cerebral venous saturation and OEF were the only hemodynamic correlate of TOI. Total hemoglobin and percent sickle hemoglobin were equally and independently correlated with TOI with a combined r2 of 0.59 on multivariate regression (p<0.0001). Discussion This represents the first study comparing TOI to direct measurements of cerebral oxygen supply and consumption in SCD patients. We demonstrate that TOI tracks SvO2 and OEF, suggesting that it is weighted toward venous vascular beds. The relationship of TOI and HbS% has been previously described and could either shifting of the oxygen dissociation curve or mechanical disruption of microvascular integrity. TOI's strong dependence on total hemoglobin (after correction for HbS%) is particularly startling given its independence with oxygen delivery, suggesting that total hemoglobin is acting as a surrogate marker of microvascular disease severity in SCD patients. TableParameterR2pAge (Years)0.0127nsHemoglobin (gm/dl)0.295<0.05Hemoglobin S %0.229<0.05WBC (103/uL)0.0020nsCBF ml/100g/min0.018nsSaO2 (%)0.034nsO2 delivery0.071nsSvO2 (%)0.290<0.05OEF (%)0.238<0.05CMR020.112ns Disclosures Coates: novartis: Honoraria, Speakers Bureau; shire: Consultancy, Honoraria; apo pharma: Consultancy, Honoraria, Speakers Bureau; acceleron: Consultancy, Honoraria.

Sildenafil improves microvascular O2 delivery-to-utilization matching and accelerates exercise O2 uptake kinetics in chronic heart failure

2012 ◽  
Vol 303 (12) ◽  
pp. H1474-H1480 ◽  
Author(s):  
Priscila A. Sperandio ◽  
Mayron F. Oliveira ◽  
Miguel K. Rodrigues ◽  
Danilo C. Berton ◽  
Erika Treptow ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Exercise Tolerance ◽  
Near Infrared ◽  
Vastus Lateralis ◽  
Beneficial Effects ◽  
Subsequent Response ◽  
Constant Work Rate ◽  
No Bioavailability ◽  
O2 Delivery

Nitric oxide (NO) can temporally and spatially match microvascular oxygen (O2) delivery (Q̇o2mv) to O2 uptake (V̇o2) in the skeletal muscle, a crucial adjustment-to-exercise tolerance that is impaired in chronic heart failure (CHF). To investigate the effects of NO bioavailability induced by sildenafil intake on muscle Q̇o2mv-to-O2 utilization matching and V̇o2 kinetics, 10 males with CHF (ejection fraction = 27 ± 6%) undertook constant work-rate exercise (70–80% peak). Breath-by-breath V̇o2, fractional O2 extraction in the vastus lateralis {∼deoxygenated hemoglobin + myoglobin ([deoxy-Hb + Mb]) by near-infrared spectroscopy}, and cardiac output (CO) were evaluated after sildenafil (50 mg) or placebo. Sildenafil increased exercise tolerance compared with placebo by ∼20%, an effect that was related to faster on- and off-exercise V̇o2 kinetics ( P < 0.05). Active treatment, however, failed to accelerate CO dynamics ( P > 0.05). On-exercise [deoxy-Hb + Mb] kinetics were slowed by sildenafil (∼25%), and a subsequent response “overshoot” ( n = 8) was significantly lessened or even abolished. In contrast, [deoxy-Hb + Mb] recovery was faster with sildenafil (∼15%). Improvements in muscle oxygenation with sildenafil were related to faster on-exercise V̇o2 kinetics, blunted oscillations in ventilation ( n = 9), and greater exercise capacity ( P < 0.05). Sildenafil intake enhanced intramuscular Q̇o2mv-to-V̇o2 matching with beneficial effects on V̇o2 kinetics and exercise tolerance in CHF. The lack of effect on CO suggests that improvement in blood flow to and within skeletal muscles underlies these effects.

Sign in / Sign up

Export Citation Format

Share Document