Absolute total hemoglobin mass (tHbmass) and blood compartment volumes are often considered to be higher in endurance athletes compared with nonathletes, yet little data support a fitness effect in ...older age. Therefore, we measured tHbmass and blood compartment volumes (carbon monoxide rebreathing) in 77 healthy individuals (23% female; aged, 60-87 yr). Participants were recruited into groups based upon their lifelong (>25 yr) exercise "dose":
) 15 sedentary individuals, <2 sessions/wk;
) 25 casual exercisers, 2-3 sessions/wk;
) 24 committed exercisers, 4-5 sessions/wk; and
) 13 competitive Masters athletes, 6-7 sessions/wk, plus regular competitions. Absolute (L/min) and relative (mL/kg/min) V̇o
were higher with increasing exercise "dose" (
= 0.0005 and
< 0.0001, respectively). Hemoglobin concentration, hematocrit, and absolute tHbmass and blood compartment volumes were not significantly different between groups (all,
> 0.1328). When scaled to body mass, tHbmass (Sedentary, 9.2 ± 1.7 mL/kg; Casual, 9.2 ± 1.3; Committed, 10.2 ± 1.4; Competitive, 11.5 ± 1.4, ANOVA
< 0.0001) and blood volume were significantly different between groups Sedentary, 63.4 (59.2-68.5) mL/kg; Casual, 67.3 (64.4-72.6); Committed, 73.5 (67.5-80.2); Competitive, 83.4 (78.9-88.6), ANOVA
< 0.0001, whereby all values were highest in Masters athletes. However, when scaled to fat-free mass (FFM), tHbmass and blood compartment volumes were greater in Competitive compared with Casual exercisers (all,
< 0.0340) and tHbmass and erythrocyte volume were also higher in Committed compared with Casual exercisers (both,
< 0.0134). In conclusion, absolute tHbmass and blood compartment volumes are not different between groups, with dose-dependent differences only among exercisers when scaled for FFM, with the highest tHbmass and blood compartment volumes in competitive Masters athletes.
We observed that absolute oxygen carrying capacity (total hemoglobin mass, tHbmass) and blood compartment volumes were not associated with lifelong exercise dose. However, hematological adaptations associated with lifelong habitual exercise are only present among exercisers, whereby competitive Masters athletes have a greater oxygen carrying capacity (tHbmass) and expanded blood compartment volumes when scaled to fat-free mass.
The regulation of skeletal muscle blood flow and oxygen delivery to contracting skeletal muscle is complex and involves the mechanical effects of muscle contraction; local metabolic, red blood cell ...and endothelium‐derived substances; and the sympathetic nervous system (SNS). With advancing age in humans, skeletal muscle blood flow is typically reduced during dynamic exercise and this is due to a lower vascular conductance, which could ultimately contribute to age‐associated reductions in aerobic exercise capacity, a primary predictor of mortality in both healthy and diseased ageing populations. Recent findings have highlighted the contribution of endothelium‐derived substances to blood flow control in contracting muscle of older adults. With advancing age, impaired nitric oxide availability due to scavenging by reactive oxygen species, in conjunction with elevated vasoconstrictor signalling via endothelin‐1, reduces the local vasodilatory response to muscle contraction. Additionally, ageing impairs the ability of contracting skeletal muscle to blunt sympathetic vasoconstriction (i.e. ‘functional sympatholysis’), which is critical for the proper regulation of tissue blood flow distribution and oxygen delivery, and could further reduce skeletal muscle perfusion during high intensity and/or large muscle mass exercise in older adults. We propose that initiation of endothelium‐dependent hyperpolarization is the underlying signalling event necessary to properly modulate sympathetic vasoconstriction in contracting muscle, and that age‐associated impairments in red blood cell adenosine triphosphate release and stimulation of endothelium‐dependent vasodilatation may explain impairments in both local vasodilatation and functional sympatholysis with advancing age in humans.
Simplified schematic diagram depicting the effects of impaired skeletal muscle vascular control with age in humans.
Key points
This study examined the effect of different ‘doses’ of lifelong (>25 years) exercise on arterial stiffening (a hallmark of vascular ageing) in older adults.
There are clear dose‐dependent ...effects of lifelong exercise training on human arterial stiffness that vary according to the site and size of the arteries.
Similar to what we have observed previously with ventricular stiffening, 4–5 days week−1 of committed exercise over a lifetime are necessary to preserve ‘youthful’ vascular compliance, especially of the large central arteries.
Casual exercise training of two to three times per week may be sufficient for middle‐sized arteries like the carotid to minimize arterial stiffening with ageing.
However, there is little effect of exercise training on the small‐sized peripheral arteries at any dose.
Central arterial stiffness increases with sedentary ageing. While near‐daily, vigorous lifelong (>25 years) endurance exercise training prevents arterial stiffening with ageing, this rigorous routine of exercise training over a lifetime is impractical for most individuals. The aim was to examine whether a less frequent ‘dose’ of lifelong exercise training (four to five sessions per week for > 30 min) that is consistent with current physical activity recommendations elicits similar benefits on central arterial stiffening with ageing. A cross‐sectional examination of 102 seniors (>60 years old) who had a consistent lifelong exercise history was performed. Subjects were stratified into four groups based on exercise frequency as an index of exercise ‘dose’: sedentary: fewer than two sessions per week; casual exercisers: two to three sessions per week; committed exercisers: four to five sessions per week; and Masters athletes: six to seven sessions per week plus regular competitions. Detailed measurements of arterial stiffness and left ventricular afterload were collected. Biological aortic age and central pulse wave velocity were younger in committed exercisers and Masters athletes compared to sedentary seniors. Total arterial compliance index (TACi) was lower, while carotid β‐stiffness index and effective arterial elastance were higher in sedentary seniors compared to the other groups. There appeared to be a dose–response threshold for carotid β‐stiffness index and TACi. Peripheral arterial stiffness was not significantly different among the groups. These data suggest that four to five weekly exercise sessions over a lifetime is associated with reduced central arterial stiffness in the elderly. A less frequent dose of lifelong exercise (two to three sessions per week) is associated with decreased ventricular afterload and peripheral resistance, while peripheral arterial stiffness is unaffected by any dose of exercise.
Key points
This study examined the effect of different ‘doses’ of lifelong (>25 years) exercise on arterial stiffening (a hallmark of vascular ageing) in older adults.
There are clear dose‐dependent effects of lifelong exercise training on human arterial stiffness that vary according to the site and size of the arteries.
Similar to what we have observed previously with ventricular stiffening, 4–5 days week−1 of committed exercise over a lifetime are necessary to preserve ‘youthful’ vascular compliance, especially of the large central arteries.
Casual exercise training of two to three times per week may be sufficient for middle‐sized arteries like the carotid to minimize arterial stiffening with ageing.
However, there is little effect of exercise training on the small‐sized peripheral arteries at any dose.
Compression sonography has been proposed as a method for non‐invasive measurement of venous pressures during spaceflight, but initial reports of venous pressure measured by compression ultrasound ...conflict with prior reports of invasively measured central venous pressure (CVP). The aim of this study is to determine the agreement of compression sonography of the internal jugular vein (IJVP) with invasive measures of CVP over a range of pressures relevant to microgravity exposure. Ten healthy volunteers (18–55 years, five female) completed two 3‐day sessions of supine bed rest to simulate microgravity. IJVP and CVP were measured in the seated position, and in the supine position throughout 3 days of bed rest. The range of CVP recorded was in line with previous reports of CVP during changes in posture on Earth and in microgravity. The correlation between IJVP and CVP was poor when measured during spontaneous breathing (r = 0.29; R2 = 0.09; P = 0.0002; standard error of the estimate (SEE) = 3.0 mmHg) or end‐expiration CVP (CVPEE; r = 0.19; R2 = 0.04; P = 0.121; SEE = 3.0 mmHg). There was a modest correlation between the change in CVP and the change in IJVP for both spontaneous ΔCVP (r = 0.49; R2 = 0.24; P < 0.0001) and ΔCVPEE (r = 0.58; R2 = 0.34; P < 0.0001). Bland–Altman analysis of IJVP revealed a large positive bias compared to spontaneous breathing CVP (3.6 mmHg; SD = 4.0; CV = 85%; P < 0.0001) and CVPEE (3.6 mmHg; SD = 4.2; CV = 84%; P < 0.0001). Assessment of absolute IJVP via compression sonography correlated poorly with direct measurements of CVP by invasive catheterization over a range of venous pressures that are physiologically relevant to spaceflight. However, compression sonography showed modest utility for tracking changes in venous pressure over time.
New Findings
What is the central question of this study?
Compression sonography has been proposed as a novel method for non‐invasive measurement of venous pressures during spaceflight. However, the accuracy has not yet been confirmed in the range of CVP experienced by astronauts during spaceflight.
What is the main finding and its importance?
Our data show that compression sonography of the internal jugular vein correlates poorly with direct measurement of central venous pressures in a range that is physiologically relevant to spaceflight. However, compression sonography showed modest utility for tracking changes in venous pressure over time.
Heart failure with preserved ejection fraction (HFpEF) accounts for over 50% of all heart failure cases nationwide and continues to rise in its prevalence. The complex, multi‐organ involvement of the ...HFpEF clinical syndrome requires clinicians and investigators to adopt an integrative approach that considers the contribution of both cardiac and non‐cardiac function to HFpEF pathophysiology. Thus, this symposium review outlines the key points from presentations covering the contributions of disease‐related changes in cardiac function, arterial stiffness, peripheral vascular function, and oxygen delivery and utilization to exercise tolerance in patients with HFpEF. While many aspects of HFpEF pathophysiology remain poorly understood, there is accumulating evidence for a decline in vascular health in this patient group that may be remediable through pharmacological and lifestyle interventions and could improve outcomes and clinical status in this ever‐growing patient population.
What is the topic of this review?
This symposium review provides an integrative view of how disease‐related changes in cardiac, vascular and skeletal muscle function contribute to exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF).
What advances does it highlight?
Emerging evidence continues to highlight the importance of considering both cardiac and non‐cardiac abnormalities in patients with HFpEF, with accumulating evidence for ‘plasticity’ in vascular function that emphasizes the need for a greater focus on strategies targeting the peripheral circulation as a means to improve exercise intolerance.
Reductions in arterial SIRT1 expression and activity with aging are linked to vascular endothelial dysfunction. We tested the hypothesis that the specific SIRT1 activator SRT1720 improves endothelial ...function endothelium-dependent dilation (EDD) in old mice. Young (4-9 mo) and old (29-32 mo) male B6D2F1 mice treated with SRT1720 (100 mg/kg body wt) or vehicle for 4 wk were studied with a group of young controls. Compared with the young controls, aortic SIRT1 expression and activity were reduced (P < 0.05) and EDD was impaired (83 ± 2 vs. 96 ± 1%; P < 0.01) in old vehicle-treated animals. SRT1720 normalized SIRT1 expression/activity in old mice and restored EDD (95 ± 1%) by enhancing cyclooxygenase (COX)-2-mediated dilation and protein expression in the absence of changes in nitric oxide bioavailability. Aortic superoxide production and expression of NADPH oxidase 4 (NOX4) were increased in old vehicle mice (P < 0.05), and ex vivo administration of the superoxide scavenger TEMPOL restored EDD in that group. SRT1720 normalized aortic superoxide production in old mice, without altering NOX4 and abolished the improvement in EDD with TEMPOL, while selectively increasing aortic antioxidant enzymes. Aortic nuclear factor-κB (NF-κB) activity and tumor necrosis factor-α (TNF-α) were increased in old vehicle mice (P < 0.05), whereas SRT1720 normalized NF-κB activation and reduced TNF-α in old animals. SIRT1 activation with SRT1720 ameliorates vascular endothelial dysfunction with aging in mice by enhancing COX-2 signaling and reducing oxidative stress and inflammation. Specific activation of SIRT1 is a promising therapeutic strategy for age-related endothelial dysfunction in humans.
Sympathetic transduction is reduced following chronic high-altitude (HA) exposure; however, vascular α-adrenergic signaling, the primary mechanism mediating sympathetic vasoconstriction at sea level ...(SL), has not been examined at HA. In nine male lowlanders, we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (ΔFVC) during
) incremental intra-arterial infusion of phenylephrine to assess α
-adrenergic receptor responsiveness and
) combined intra-arterial infusion of β-adrenergic and α-adrenergic antagonists propranolol and phentolamine (α-β-blockade) to assess adrenergic vascular restraint at rest and during exercise-induced sympathoexcitation (cycling; 60% peak power). Experiments were performed near SL (344 m) and after 3 wk at HA (4,383 m). HA abolished the vasoconstrictor response to low-dose phenylephrine (ΔFVC: SL: -34 ± 15%, vs. HA;
3 ± 18%;
< 0.0001) and markedly attenuated the response to medium (ΔFVC: SL: -45 ± 18% vs. HA: -28 ± 11%;
= 0.009) and high (ΔFVC: SL: -47 ± 20%, vs. HA: -35 ± 20%;
= 0.041) doses. Blockade of β-adrenergic receptors alone had no effect on resting FVC (
= 0.500) and combined α-β-blockade induced a similar vasodilatory response at SL and HA (
= 0.580). Forearm vasoconstriction during cycling was not different at SL and HA (
= 0.999). Interestingly, cycling-induced forearm vasoconstriction was attenuated by α-β-blockade at SL (ΔFVC: Control: -27 ± 128 vs. α-β-blockade: +19 ± 23%;
= 0.0004), but unaffected at HA (ΔFVC: Control: -20 ± 22 vs. α-β-blockade: -23 ± 11%;
= 0.999). Our results indicate that in healthy males, altitude acclimatization attenuates α
-adrenergic receptor responsiveness; however, resting α-adrenergic restraint remains intact, due to concurrent resting sympathoexcitation. Furthermore, forearm vasoconstrictor responses to cycling are preserved, although the contribution of adrenergic receptors is diminished, indicating a reliance on alternative vasoconstrictor mechanisms.
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