Plantar Flexion Exercise Research Articles

Mitochondrial oxidative phosphorylation capacity in skeletal muscle measured by ultrafast Z-spectroscopy (UFZ) MRI at 3T.

To investigate the feasibility of rapid CEST MRI acquisition for evaluating oxidative phosphorylation (OXPHOS) in human skeletal muscle at 3T, utilizing ultrafast Z-spectroscopy (UFZ) combined with MRI and the Polynomial and Lorentzian line-shape Fitting (PLOF) technique. UFZ MRI on muscle was evaluated with turbo spin echo (TSE) and 3D EPI readouts. Five healthy subjects performed in-magnet plantar flexion exercise (PFE) and subsequent changes of amide, PCr, and partial PCr mixed Cr (Cr+) CEST dynamic signals post-exercise were enabled by PLOF fitting. PCr/Cr CEST signal was further refined through pH correction by using the ratios between PCr/Cr and amide signals, named PCAR/CAR, respectively. UFZ MRI with TSE readout significantly reduces acquisition time, achieving a temporal resolution of <50 s for collecting high-resolution Z-spectra. Following PFE, the recovery/decay times (τ) for both PCr and Cr in the gastrocnemius muscle of the calf were notably longer when determined using PCr/Cr CEST compared to those after pH correction with amideCEST, namely = 87.1 ± 15.8 s and = 98.1 ± 20.4 s versus = 32.9 ± 19.7 s and = 43.0 ± 13.0 s, respectively. obtained via 31P MRS ( = 50.3 ± 6.2 s) closely resemble those obtained from pH-corrected PCr/Cr CEST signals. The outcomes suggest potential of UFZ MRI as a robust tool for non-invasive assessment of mitochondrial function in skeletal muscles. pH correction is critical for the reliable OXPHOS measurement by CEST.

The human lower leg muscle pump functions as a flow diverter pump, maintaining low ambulatory venous pressures during locomotion

ObjectiveAmbulatory venous pressure (AVP) is the drop of pressure observed in the superficial veins of the lower leg during movement. This phenomenon has been linked to the function of the calf muscle pump (CMP) and the competence of venous valves. Nevertheless, the concept of the CMP function remains controversial. This study aimed to elucidate the association between lower leg muscles activity, changes in pressure in distinct venous segments, and lower extremity arterial blood supply in healthy subjects during various types and intensities of exercise. MethodsTwelve legs of nine healthy volunteers were enrolled in the study. Continuous pressure (intramuscular vein [IV] and three great saphenous vein [GSV] points) and surface electromyography data (gastrocnemius and anterior tibial [ATM] muscles) were recorded during treadmill walking, running, and plantar flexion exercises. The pressure gradient (ΔP, mmHg) between adjacent points of measurement was calculated. Minute unit power of muscle pump ejection and suction (NE, and NS, MPa/min) were calculated and compared with the arterial blood supply of the lower extremity (LBF, L/min). ResultsΔP demonstrated a consistent pattern of changes during walking and running. In GSV, the ΔP was observed to be directed from the thigh to the mid-calf (retrogradely) and from the ankle to the mid-calf (anterogradely) throughout the entire stride cycle. However, its value decreased with increasing stride cycle frequency. The dynamics of ΔP between the IV and GSV were as follows: It was directed from the IV to GSV during gastrocnemius contraction and was reversed during anterior tibial muscle contraction and gastrocnemius relaxation (swing phase). LBF, NE, and NS demonstrated similar exponential growth with increasing stride frequency during walking and running. ConclusionsDuring natural locomotion, the muscle pump acts as a flow diverter pump, redirecting the flow of blood from the superficial veins to the intramuscular veins via the perforating veins. During ambulation, the pressure in the superficial venous network depends upon the capacity of the muscle pump to provide output that matches the changes in arterial blood flow.

Reliability of In Vivo Creatine-Weighted Chemical Exchange Saturation Transfer (CrCEST) MRI in Calf Skeletal Muscle of Healthy Volunteers at 3 T.

Skeletal muscle mitochondrial oxidative phosphorylation (mtOXPHOS) is important for ATP generation and its dysfunction leads to exercise intolerance. Phosphorus magnetic resonance spectroscopy (31P-MRS) is a useful, noninvasive technique for mtOXPHOS assessment but has limitations. Creatine-weighted chemical exchange saturation transfer (CrCEST) MRI is a potential alternative to assess muscle bioenergetics. To evaluate the interscan repeatability, intra- and interobserver reproducibility of CrCEST during mild plantar flexion exercise. Retrospective. Twenty healthy volunteers (age 37.6 ± 12.4 years, 11 females). 3 T/CEST imaging using gradient echo readout. τCrCEST (postexercise Cr recovery time) was assessed in two scans for each participant, following mild plantar flexion exercises targeting the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (Sol) muscles. Three observers measured τCrCEST for interobserver reproducibility. Three readings by one observer were used to measure intraobserver reproducibility. Two scans were used for within-participant interscan repeatability. Paired t tests, intraclass correlation coefficient (ICC), and Pearson correlation were conducted. Bland-Altman plots were used to analyze the interobserver variability. A P-value of 0.05 was considered statistically significant. There was excellent intra- (ICC ) and interobserver (ICC ) reproducibility, with moderate interscan repeatability for τCrCEST in LG and MG (ICC ) and poor-to-moderate interscan repeatability in Sol (ICC ). Excellent interobserver reproducibility was confirmed by Bland-Altman plots (fixed bias P-value ). CrCEST MRI shows promise in assessing muscle bioenergetics by evaluating τCrCEST during mild plantar flexion exercise with reasonable reliability, particularly in LG and MG. 4 TECHNICAL EFFICACY: Stage 1.

Muscle Mitochondrial Capacity Is Impaired Immediately Following Maximal Exercise.

This study measured the time course mVO2max following both maximal and submaximal exercise. Healthy male and female participants were tested (n = 12 maximal and n = 8 submaximal exercise). A NIRS device was placed on the left medial gastrocnemius. Participants performed either one minute of maximal, rapid (~2 Hz), or submaximal (~0.37 Hz) plantar flexion exercise on a custom pneumatic ergometer. mVO2max was measured before and immediately after exercise. mVO2max measurements consisted of four incomplete recovery curves of muscle metabolism taken after 30 seconds of electrical muscle stimulation except in the first post-exercise trial. The four recovery curves were collected 50-, 156-, 260-, and 366-seconds post-exercise, each producing a mVO2max rate constant. After maximal exercise muscle acceleration decreased to 52 + 18% (p = 0.001) of pre-values. mVO2max was reduced from the pre-exercise mean at the first post-trial (2.16 + 0.44 min-1 to 1.21 + 0.52 min -1, p < 0.001). The fourth trial showed recovery from the first (2.2 + 0.46 min-1 vs 1.21 + 0.52 min-1, p < 0.001) and was not significantly different from pre-exercise values (2.2 + 0.46 min-1 vs 2.16 + 0.44 min-1, p = 0.41). No change in acceleration or mVO2max was seen after submaximal exercise (p > 0.05). The 56.7% reduction in mVO2max supports the hypothesis that in young, healthy individuals a minute of maximal exercise transiently impairs mVO2max which then recovers within six minutes. The NIRS method shows promise in tracking time course changes in mVO2max and warrants further investigation of the transient effects of exercise on mVO2max.

Effects of short-term dietary nitrate supplementation on exercise and coronary blood flow responses in patients with peripheral artery disease.

Peripheral arterial disease (PAD) is a prevalent vascular disorder characterized by atherosclerotic occlusion of peripheral arteries, resulting in reduced blood flow to the lower extremities and poor walking ability. Older patients with PAD are also at a markedly increased risk of cardiovascular events, including myocardial infarction. Recent evidence indicates that inorganic nitrate supplementation, which is abundant in certain vegetables, augments nitric oxide (NO) bioavailability and may have beneficial effects on walking, blood pressure, and vascular function in patients with PAD. We sought to determine if short-term nitrate supplementation (via beetroot juice) improves peak treadmill time and coronary hyperemic responses to plantar flexion exercise relative to placebo (nitrate-depleted juice) in older patients with PAD. The primary endpoints were peak treadmill time and the peak coronary hyperemic response to plantar flexion exercise. Eleven PAD patients (52-80 yr.; 9 men/2 women; Fontaine stage II) were randomized (double-blind) to either nitrate-rich (Beet-IT, 0.3 g inorganic nitrate twice/day; BRnitrate) or nitrate-depleted (Beet-IT, 0.04 g inorganic nitrate twice/day, BRplacebo) beetroot juice for 4 to 6 days, followed by a washout of 7 to 14 days before crossing over to the other treatment. Patients completed graded plantar flexion exercise with their most symptomatic leg to fatigue, followed by isometric handgrip until volitional fatigue at 40% of maximum on day 4 of supplementation, and a treadmill test to peak exertion 1-2 days later while continuing supplementation. Hemodynamics and exercise tolerance, and coronary blood flow velocity (CBV) responses were measured. Although peak walking time and claudication onset time during treadmill exercise did not differ significantly between BRplacebo and BRnitrate, the diastolic blood pressure response at the peak treadmill walking stage was significantly lower in the BRnitrate condition. Increases in CBV from baseline to peak plantar flexion exercise after BRplacebo and BRnitrate showed a trend for a greater increase in CBV at the peak workload of plantar flexion with BRnitrate (p = 0.06; Cohen's d = 0.56). Overall, these preliminary findings suggest that inorganic nitrate supplementation in PAD patients is safe, well-tolerated, and may improve the coronary hyperemic and blood pressure responses when their calf muscles are most predisposed to ischemia.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT02553733.

OS CARACTERES SEMIOLOGICOS DA DOENÇA VENOSA CRÔNICA

Chronic venous insufficiency is mostly idiopathic in nature and, in these cases, is called primary insufficiency. Another large part of cases of venous insufficiency is a consequence of a sequelae of DVT, in which case the venous insufficiency is called secondary. The striking clinical characteristics of venous insufficiency include: a feeling of tiredness or pain in the legs and edema that worsen in na upright position, more evident in the afternoon. Symptoms improve with elevation of the limb. Late changes in venous insufficiency include skin hyperpigmentation, lipodermatosclerosis and venous ulcers. The diagnosis is clinical and can be confirmed using color Doppler ultrasound. All patients with venous insufficiency should be treated by applying elastic stockings or compression bandages, in addition to elevating the limb three to four times a day, plantar flexion exercises and skin care. Venous ulcers should be treated using the same general measures recommended for chronic venous insufficiency, in addition to local wound care, such as dressing changes and debridement of devitalized tissues. The use of systemic antibiotic therapy is only foreseen in the presence of na active infection.

L-Citrulline Supplementation Improves Leg Endothelial Function and Blood Flow Responses to Plantarflexion Exercise in Hypertensive Postmenopausal Women

Menopause and hypertension are associated with macro- and microvascular endothelial dysfunction at rest. Arginine deficiency and low nitric oxide (NO) synthesis may contribute to reduced muscle blood flow (BF) and oxygen delivery to exercising muscles. Improving BF to calf muscles may enhance physical activity. L-Citrulline supplementation (CIT) has improved resting macrovascular endothelial function via increased arginine availability for NO synthesis. Thus, the purpose of this study was to examine the effects of CIT on resting microvascular endothelial function and BF responses to plantarflexion exercise (PFE) in hypertensive postmenopausal women. We hypothesized that CIT would improve microvascular function and BF responses to PFE compared to placebo (PL). Twenty-one hypertensive postmenopausal women were randomized to 4 weeks of CIT (10g/day, n=10) or PL ( n=11). Superficial femoral macro- (flow-mediated dilation; FMD) and microvascular function (5s average peak blood velocity and flow during reperfusion) were assessed by ultrasound at 0 and 4 weeks. Femoral artery BF and vascular conductance (VC) were measured via ultrasound at rest and during 3-minute stages of rhythmic PFE at 5%, 15%, and 30% of 1-repetition maximum (1RM) at 0 and 4 weeks. BF and VC responses to PFE were analyzed as the change from rest to the last minute of each stage. There were no differences between groups in FMD, 5s peak velocity and flow during reperfusion, and vascular responses to PFE at 0 weeks. CIT significantly increased FMD (CIT:Δ1.28 ± 0.42 vs PL:Δ0.01 ± 0.40%, p = 0.04) and 5s peak velocity (CIT:Δ17.44 ± 4.21 vs PL:Δ0.09 ± 4.01 cm/s, p = 0.01) and flow (CIT:Δ220 ± 54 vs PL:Δ35 ± 51 mL/min, p = 0.02) during reperfusion compared to PL. CIT had no effect on BF and VC responses to 5% PFE ( p &gt; 0.05). CIT significantly augmented BF responses to 15% PFE (CIT:Δ82 ± 16 vs PL:Δ22 ± 15 mL/min, p &lt; 0.01) and 30% PFE (CIT:Δ156 ± 33 vs PL:Δ38 ± 32 mL/min, p &lt; 0.01) and VC responses to 15% PFE (CIT:Δ0.80 ± 0.16 vs PL:Δ0.11 ± 0.15 mL*100mmHg/min, p &lt; 0.01) and 30% PFE (CIT:Δ1.49 ± 0.29 vs PL:Δ0.24 ± 0.27 mL*100mmHg/min, p &lt; 0.01) compared to PL. Improvements in FMD were not correlated with BF or VC responses to PFE ( p &gt; 0.05). Improvements in 5s peak velocity were positively correlated with BF responses to 15% PFE ( r = 0.498, p = 0.02) and 30% PFE ( r = 0.532, p = 0.01), and with VC responses to 15% PFE ( r = 0.542, p = 0.01) and 30% PFE ( r = 0.633, p &lt; 0.01). Similarly, augmented 5s flow was positively correlated with BF ( r = 0.461, p = 0.04) and VC ( r = 0.558, p = 0.01) responses to 30% PFE. These findings indicate that CIT improved superficial femoral artery macro- and microvascular endothelial function at rest. However, only improvements in microvascular endothelial function influenced vascular function during leg exercise in hypertensive postmenopausal women. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Postmenopausal Women with Obesity have Reduced Leg Endothelial Function and Exercise Vasodilatory Capacity

Background: Obesity (OB) is highly prevalent in postmenopausal women; particularly increased abdominal visceral adipose tissue contributes to endothelial dysfunction and cardiovascular risk. The endothelium plays an important role on blood flow (BF) and pressure control at rest and during exercise. However, it is unknown how different body mass index (BMI) categories influence upper and lower limb endothelial function and BF responses to exercise in postmenopausal women. Purpose: The purpose was to examine upper and lower limb endothelial function at rest and BF regulation during low-intensity exercises in OB, overweight (OW), and lean (LN) postmenopausal women. We hypothesized that endothelial function and BF responses to submaximal exercise in both limbs will be attenuated in OB compared to the OW and LN groups. Methods: Women were classified as OB (30.0-39.9 kg/m2; n = 13), OW (25.0-29.9 kg/m2; n = 15), and LN (18.5-24.9 kg/m2; n = 11) by BMI. Flow-mediated dilation (FMD) of the brachial (BA-FMD) and superficial femoral arteries (FA-FMD) were measured using ultrasound. BF and vascular conductance (VC) in the brachial (BA-BF and BA-VC) and femoral (FA-BF and FA-VC) arteries were measured during separate 3-stage incremental rhythmic handgrip and plantarflexion exercises (PFE) at 5, 15, and 30 % of maximal strength and calculated 1-repetition max (1RM), respectively. Results: No differences in BA-FMD were observed among the groups. FA-FMD was significantly lower in OB (2.6 ± 1.4%) compared to OW (4.3 ± 1.9%) and LN (4.2 ± 0.7%) groups (P &lt; 0.05). Increases in FA-BF (OB: 462 ± 229 vs. OW: 616 ± 173 vs. LN: 640 ± 141 mL/min; P &lt; 0.001) and FA-VC (OB: 410 ± 176 vs. OW: 585 ± 155 vs LN: 623 ± 153 mL/min*100mmHg; P &lt; 0.001) were attenuated during PFE at 30% of 1RM in OB compared to OW and LN. Upper-body exercise vasodilation was not attenuated by OB. FA-BF and FA-VC during PFE at 30% of 1RM were correlated with FA-FMD (FA-BF: r = 0.423, P = 0.007, FA-VC: r = 0.367, P = 0.021) and BMI (FA-BF: r = -.386, P = 0.015, FA-VC: r = -.456, P = 0.004). Conclusion: Postmenopausal women with OB have blunted leg endothelial function and exercise vasodilator function during submaximal dynamic plantarflexion exercise compared to LN and OW. These findings suggest that OB may contribute to reduce leg endothelial function, and vasodilator function during exercise in postmenopausal women. No support of funding information to disclose. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Quantifying in vivo Mitochondrial Effciency at Rest and during Exercise in Human Skeletal Muscle

Introduction: Mitochondrial effciency provides an additional mechanism to fine-tune oxidative phosphorylation rate to match ATP demand in skeletal muscle with far-reaching consequences on exercise tolerance. However, the direct measurement of both oxygen consumption (VO2) and ATP production from the same region of the contracting muscle in vivo remains a technical challenge. Purpose: Using an innovative approach combining noninvasive phosphorus and proton magnetic resonance spectroscopy (31P/1H-MRS), the present study aimed to characterize skeletal muscle ATP synthesis rate and muscle VO2 at rest and during a graded dynamic plantar flexion exercise to determine mitochondrial effciency in the gastrocnemius muscle. Method: We assessed mitochondrial effciency in the gastrocnemius muscles of 12 healthy adults (21± 1 yrs.). 31P and 1H magnetic resonance spectroscopy (MRS) was performed using a whole-body 3T MR system (Skyra, Siemens) at rest and during a series of constant workloads coupled to brief transient ischemia to quantify both oxidative ATP synthesis (ATPox) rate and myoglobin-derived oxygen consumption (Mb-derived VO2). The MRS data were acquired with a dual-tuned 31P/1H surface coil with linear polarization positioned over the gastrocnemius muscle. Results: As expected, the end-exercise PCr concentration decreased from 29 ± 2 mM of WRmax to 18 ± 1 mM with increasing workload. Likewise, the end-exercise Mb oxygenation level declined linearly with increasing workload. As the exercise workload increased, the ATPox synthesis rate increased linearly (r2 = 0.45), whereas there was no significant change in Mb-derived VO2. At rest, the estimated P/O ratio in the gastrocnemius muscle was 1.95 ± 0.68, whereas non-physiological values were obtained during exercise. Conclusion: During exercise, Mb-derived VO2 was likely limited by O2 availability with the methodology employed (30-sec occlusion, spectrum time resolution of 10 sec), which precluded the accurate quantification of mitochondrial effciency. However, mitochondrial effciency calculated at rest is in agreement with previously documented values ex vivo and thus provides an additional parameter to evaluate mitochondrial function in vivo. This work was funded in part by National Heart, Lung, and Blood Institute Grant R00HL125756. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Association between dietary phosphate intake and skeletal muscle energetics in adults without cardiovascular disease.

Highly bioavailable inorganic phosphate (Pi) is present in large quantities in the typical Western diet and represents a large fraction of total phosphate intake. Dietary Pi excess induces exercise intolerance and skeletal muscle mitochondrial dysfunction in normal mice. However, the relevance of this to humans remains unknown. The study was conducted on 13 individuals without a history of cardiopulmonary disease (46% female, 15% Black participants) enrolled in the pilot-phase of the Dallas Heart and Mind Study. Total dietary phosphate was estimated from 24-h dietary recall (ASA24). Muscle ATP synthesis was measured at rest, and phosphocreatinine (PCr) dynamics was measured during plantar flexion exercise using 7-T 31P magnetic resonance (MR) spectroscopy in the calf muscle. Correlation was assessed between dietary phosphate intake normalized to total caloric intake, resting ATP synthesis, and PCr depletion during exercise. Higher dietary phosphate intake was associated with lower resting ATP synthesis (r = -0.62, P = 0.03), and with higher levels of PCr depletion during plantar flexion exercise relative to the resting period (r = -0.72; P = 0.004). These associations remain significant after adjustment for age and estimated glomerular filtration rate (both P < 0.05). High dietary phosphate intake was also associated with lower serum Klotho levels, and Klotho levels are in turn associated with PCr depletion and higher ADP accumulation post exercise. Our study suggests that higher dietary phosphate is associated with reduced skeletal muscle mitochondrial function at rest and exercise in humans providing new insight into potential mechanisms linking the Western diet to impaired energy metabolism.NEW & NOTEWORTHY This is the first translational research study directly demonstrating the adverse effects of dietary phosphate on muscle energy metabolism in humans. Importantly, our data show that dietary phosphate is associated with impaired muscle ATP synthesis at rest and during exercise, independent of age and renal function. This is a new biologic paradigm with significant clinical dietary implications.

Correlation between skeletal muscle acetylcarnitine and phosphocreatine metabolism during submaximal exercise and recovery: interleaved 1H/31P MRS 7 T study

Acetylcarnitine is an essential metabolite for maintaining metabolic flexibility and glucose homeostasis. The in vivo behavior of muscle acetylcarnitine content during exercise has not been shown with magnetic resonance spectroscopy. Therefore, this study aimed to explore the behavior of skeletal muscle acetylcarnitine during rest, plantar flexion exercise, and recovery in the human gastrocnemius muscle under aerobic conditions. Ten lean volunteers and nine overweight volunteers participated in the study. A 7 T whole-body MR system with a double-tuned surface coil was used to acquire spectra from the gastrocnemius medialis. An MR-compatible ergometer was used for the plantar flexion exercise. Semi-LASER-localized 1H MR spectra and slab-localized 31P MR spectra were acquired simultaneously in one interleaved exercise/recovery session. The time-resolved interleaved 1H/31P MRS acquisition yielded excellent data quality. A between-group difference in acetylcarnitine metabolism over time was detected. Significantly slower τPCr recovery, τPCr on-kinetics, and lower Qmax in the overweight group, compared to the lean group was found. Linear relations between τPCr on-kinetics, τPCr recovery, VO2max and acetylcarnitine content were identified. In conclusion, we are the first to show in vivo changes of skeletal muscle acetylcarnitine during acute exercise and immediate exercise recovery with a submaximal aerobic workload using interleaved 1H/31P MRS at 7 T.

DCS blood flow index underestimates skeletal muscle perfusion in vivo: rationale and early evidence for the NIRS-DCS perfusion index.

Diffuse correlation spectroscopy (DCS) permits non-invasive assessment of skeletal muscle blood flow but may misestimate changes in muscle perfusion. We aimed to highlight recent evidence that DCS blood flow index (BFI) misestimates changes in muscle blood flow during physiological perturbation and to introduce a novel approach that adjusts BFI for estimated changes in vasodilation. We measured changes in muscle BFI during quadriceps and forearm exercises using DCS, the latter of which were adjusted for estimated changes in microvascular flow area and then compared to Doppler ultrasound in the brachial artery. Then, we compared adjusted BFI- and arterial spin labeling (ASL) MRI measures of gastrocnemius blood flow during reactive hyperemia and plantar flexion exercise. We observed little-to-no change in quadriceps BFI during maximal-effort exercise. Similarly, forearm BFI was modestly increased during handgrip exercise, but the magnitude was significantly lower than measured by Doppler ultrasound in the brachial artery. However, this difference was ameliorated after adjusting BFI for estimated changes in microvascular flow area. Similar observations were also observed in the gastrocnemius when directly comparing the adjusted BFI values to ASL-MRI. Adjusting BFI for estimated changes in microvascular flow area may improve DCS estimates of muscle blood flow, but further study is needed to validate these methods moving forward.

P047 Deconditioning in quiescent Crohn’s Disease patients with heightened fatigue perception

Abstract Background Heightened fatigue perception and premature exercise fatigue are common in inflammatory bowel disease (IBD). Physical deconditioning is greater in patients with increased fatigue perception relative to patients with a lower perception of fatigue, implicating deconditioning as an aetiological factor. This study used physiology and multiparametric Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) during exercise to comprehensively phenotype quiescent IBD fatigue. Methods Participant body mass and regional body composition was assessed by DEXA, and tknee extensor strength and fatiguability using isokinetic dynamometry (Cybex, USA). A supine CPET was performed using an MR-compatible Ergometer (Cardiostepper, Ergospect) to standardize relative exercise intensity for in-bore 1H MRI measures. 1H MRI data were collected on a Philips 3T Ingenia wide bore scanner using a Philips Head/Neck coil and in-built posterior coil. Across rest, steady-state exercise (50% VO2 peak) and recovery, Phase Contrast-MRI was used to compute cardiac output and cerebral blood flow (CBF), and T2 Relaxation under spin tagging (TRUST-MRI) to measure brain oxygen extraction fraction (OEF). 31P MRS data was collected on a 3T Philips Achieva using a 14cm 31P coil over the medial gastrocnemius. Ischaemic plantar flexion exercise was performed at 50% maximum voluntary contraction (MVC) using an MR-compatible ergometer (Trispect, Ergospect) during non-localized pulse-acquire 31P-MRS. 31P spectra were analysed using the AMARES function in jMRUI Beta 6.0. In vivo muscle mitochondrial flux during post-exercise PCr recovery (VPCr = kPCr * ΔPCr) where ΔPCr is PCrendrecovery –PCrendex) was quantified after reinstating limb blood flow and fitting PCr recovery to a mono-exponential function in GraphPad prism (PCr(t) = PCrinitial+(PCrend – PCrinitial)(1-exp(-k.t) where t is time from start of non-ischaemic recovery). Results 16 quiescent CD patients and 12 age and BMI matched HV’s completed the study. General fatigue score was greater in CD relative to HV (P = 0.001, Table 1). Body composition, isometric strength, fatigue development were not different between groups (Table 1). CBF response to steady-state exercise was less in CD (P = 0.003) alongside the maintenance of cardiac output and brain OEF in HV (Figure 1). VPCr following ischemic plantar flexion exercise was less in CD than HV (P = 0.02, Figure 1) (Figure 1). Conclusion Greater fatigue perception in CD was accompanied by lower CBF on exercise and blunted post-exercise PCr resynthesis, but no differences in body composition, strength and fatiguability relative to HV. These finding point to greater deconditioning in CD, corroborated by their lower daily step count relative to HV.

Endothelial and exercise vasodilation are reduced in postmenopausal females with obesity versus lean and overweight.

Obesity (OB) is highly prevalent in females after menopause, especially visceral adipose tissue (VAT) accumulation which contributes to endothelial dysfunction. The endothelium assists in regulating blood flow (BF) during exercise and is attenuated in females with OB. The purpose of this study was to examine upper and lower limb flow-mediated dilation (FMD) and BF regulation during graded low-intensity submaximal exercises in postmenopausal females with BMI in the lean (LN), overweight (OW) and OB categories. Participants were grouped by body mass index (BMI) into LN (BMI 18.5-24.9 kg/m2; n = 11), OW (BMI 25.0-29.9 kg/m2; n = 15), and OB (BMI 30.0-39.9 kg/m2; n = 13). FMD of the brachial (BA-FMD) and superficial femoral arteries (FA-FMD) were assessed. Subsequently, BF and vascular conductance (VC) in the upper (BA-BF and BA-VC) and lower limbs (FA-BF and FA-VC) were measured during separate 3-stage incremental rhythmic handgrip and plantarflexion exercises. Significantly lower FA-FMD (P < 0.05) were seen in OB than LN and OW groups with no differences in BA-FMD. Increases in FA-BF and FA-VC were attenuated during the last stage of plantarflexion exercise at 30% of 1RM in OB (both P < 0.001) compared to LN and OW, while upper-body exercise vasodilation was unchanged. FA-BF and FA-VC during plantarflexion exercise were correlated to FA-FMD (FA-BF: r = 0.423, P = 0.007, FA-VC: r = 0.367, P = 0.021) and BMI (FA-BF: r = -0.386, P = 0.015, FA-VC: r = -0.456, P = 0.004). Postmenopausal females with OB have reduced lower-limb endothelial and exercise vasodilator function during submaximal dynamic plantarflexion exercise compared to LN and OW. Our findings indicate that obesity may predict diminished leg endothelial function, BF and VC during exercise in postmenopausal females.

Muscle fiber strain rates in the lower leg during ankle dorsi-/plantarflexion exercise.

Static quantitative magnetic resonance imaging (MRI) provides readouts of structural changes in diseased muscle, but current approaches lack the ability to fully explain the loss of contractile function. Muscle contractile function can be assessed using various techniques including phase-contrast MRI (PC-MRI), where strain rates are quantified. However, current two-dimensional implementations are limited in capturing the complex motion of contracting muscle in the context of its three-dimensional (3D) fiber architecture. The MR acquisitions (chemical shift-encoded water-fat separation scan, spin echo-echoplanar imaging with diffusion weighting, and two time-resolved 3D PC-MRI) wereperformed at 3 T. PC-MRI acquisitions and performed with and without load at 7.5% of the maximum voluntary dorsiflexion contraction force. Acquisitions (3 T, chemical shift-encoded water-fat separation scan, spin echo-echo planar imaging with diffusion weighting, and two time-resolved 3D PC-MRI) were performed with and without load at 7.5% of the maximum voluntary dorsiflexion contraction force. Strain rates and diffusion tensors were calculated and combined to obtain strain rates along and perpendicular to the muscle fibers in seven lower leg muscles during the dynamic dorsi-/plantarflexion movement cycle. To evaluate strain rates along the proximodistal muscle axis, muscles were divided into five equal segments. t-tests were used to test if cyclic strain rate patterns (amplitude > 0) were present along and perpendicular to the muscle fibers. The effects of proximal-distal location and load were evaluated using repeated measures ANOVAs. Cyclic temporal strain rate patterns along and perpendicular to the fiber were found in all muscles involved in dorsi-/plantarflexion movement (p < 0.0017). Strain rates along and perpendicular to the fiber were heterogeneously distributed over the length of most muscles (p < 0.003). Additional loading reduced strain rates of the extensor digitorum longus and gastrocnemius lateralis muscle (p < 0.001). In conclusion, the lower leg muscles involved in cyclic dorsi-/plantarflexion exercise showed cyclic fiber strain rate patterns with amplitudes that varied between muscles and between the proximodistal segments within the majority of muscles.

Abstract 16878: Exercise Intolerance in Heart Failure With Preserved Ejection Fraction is More Closely Related to Energetic Decline During Exercise Than to Mitochondrial Oxidative Capacity in Recovery

Introduction: Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with severe exercise intolerance (EI) and exertional fatigue. Impaired skeletal muscle high-energy phosphate metabolism has been reported in HFpEF patients and postulated as a potential contributor to EI. However, whether EI is more closely related to rapid energetic decline during exercise, or reduced mitochondrial oxidative capacity remains unknown. Hypothesis: We hypothesized that six-minute walk distance (6MWD) is more closely related to the rate of skeletal muscle energetic decline during exercise than mitochondrial oxidative capacity in HFpEF. Methods: Calf muscle energetics were measured by phosphorus magnetic resonance spectroscopy ( 31 PMRS). The rate of phosphocreatine (PCr) decline normalized to work performed during graded plantar flexion exercise to volitional fatigue and the time for PCr post-exercise recovery, an established metric inversely related to mitochondrial oxidative capacity, were measured in 64 HFpEF patients (age: 65 ± 11 years; 53% women). Results: The mean rate of PCr decline, PCr recovery time, and 6MWD were 52 ± 108 μmol/g wet weight/KJ, 80 ± 45 seconds, and 296 ± 109 meters, respectively. The 6MWD was inversely related to the rate of PCr decline (r = -0.46; P = 0.0002; Figure, A ) but not significantly related to the PCr recovery time (r = -0.06; P = 0.66; Figure, B ), as determined by Pearson’s correlation coefficients. Conclusions: EI, as measured by 6MWD, in HFpEF patients is closely associated with impaired skeletal muscle metabolism, specifically rapid skeletal muscle PCr decline during exercise rather than mitochondrial oxidative capacity. This suggests that impaired glycolytic metabolism and substrate delivery may contribute metabolically to EI in HFpEF patients.

The Immediate Effect of Cumulative Transverse Strain via Exercise on the Achilles Tendon in Individuals with and Without Flat Feet.

Flat feet change lower extremity alignment, and it may change the load distribution on Achilles tendon during exercise. The purpose of the present study was to investigate the immediate effect of cumulative transverse strain via resistive ankle plantarflexion exercise on the Achilles tendon in individuals with flat feet. Fourteen individuals with flat feet and 14 age-matched individuals with normal foot posture were enrolled in the present study. Achilles tendon thickness was measured by an ultrasonography device with a linear probe at 3 points: 1 cm (AT-1), 2 cm (AT-2), and 3 cm (AT-3) proximal to the superior aspect of the calcaneus. Ultrasonography measurements were performed before and after participants completed 90 repetitions of double-leg calf raise exercises which included moving the foot from full ankle dorsiflexion to full ankle plantarflexion. Achilles tendon thickness at all points measured was thinner in the flat feet group at both pre- and post-exercise conditions compared with that of the control group (p<0.05). Achilles tendon thickness at AT-1, AT-2, and AT-3 decreased after the exercise in both groups (p<0.001). The differences in Achilles tendon thickness at all points measured between pre- and post-exercise conditions were lower in individuals with flat feet than those of the control group (p<0.05). There was a significant decrease in Achilles tendon thickness after exercise in both groups; however, the tendon thickness markedly diminished in individuals with normal foot posture. The results are thought to result from changes in tendon structure and in load distribution on the Achilles tendon.

Aortic blood pressure and pulse wave indices responses to exercise in peripheral artery disease.

Peripheral artery disease (PAD) refers to obstructed blood flow in peripheral arteries typically due to atherosclerotic plaques. How PAD alters aortic blood pressure and pressure wave propagation during exercise is unclear. Thus, this study examined central blood pressure responses to plantar flexion exercise by investigating aortic pulse wave properties in PAD. Thirteen subjects with PAD and 13 healthy [age-, sex-, body mass index (BMI) matched] subjects performed rhythmic plantar flexion for 14 min or until fatigue (20 contractions/min; started at 2 kg with 1 kg/min increment up to 12 kg). Brachial (oscillometric cuff) and radial (SphygmoCor) blood pressure and derived-aortic waveforms were analyzed during supine rest and plantar flexion exercise. At rest, baseline augmentation index (P = 0.0263) and cardiac wasted energy (P = 0.0321) were greater in PAD due to earlier arrival of the reflected wave (P = 0.0289). During exercise, aortic blood pressure (aMAP) and aortic pulse pressure showed significant interaction effects (P = 0.0041 and P = 0.0109, respectively). In particular, PAD had a greater aMAP increase at peak exercise (P = 0.0147). Moreover, the tension time index was greater during exercise in PAD (P = 0.0173), especially at peak exercise (P = 0.0173), whereas the diastolic time index (P = 0.0685) was not different between the two groups. Hence, during exercise, the subendocardial viability ratio was lower in PAD (P = 0.0164), especially at peak exercise (P = 0.0164). The results suggest that in PAD, the aortic blood pressure responses and myocardial oxygen demand during exercise are increased compared with healthy controls.

O099 A relevant metabolic model for monitoring human metabolism in vivo using dynamic nuclear polarization with 13C magnetic resonance spectroscopy

Abstract Introduction DNP increases the signal of carbon-13 molecules on MR scans (&amp;gt;10,000-fold), enabling real-time, dynamic quantitation of tissue metabolism in vivo with significant clinical potential. 13C quantification of metabolism is affected by confounding factors (T1 signal decay, flip angle, and metabolite escape), which necessitates metabolic modelling. Here, we have assessed a mathematical model that requires minimal information on confounding factors to measure metabolic rates with reliability. Methods Four healthy male volunteers (age; 24 ± 1.4 years; BMI; 23 ± 0.4 kg/m2) were recruited. Sterile hyperpolarized 13C pyruvate was safely produced using a clinical DNP polariser (SPINlab GE-Healthcare) and administered intravenously to volunteers performing in-bore plantar-flexion exercise to increase muscle pyruvate flux. 13C MR scans of the calf muscle were collected during exercise and used to test our model against 5000 computer simulations using randomised kinetic constants and confounding factors. Results The signal of metabolites was used to extract the kinetic constants of hyperpolarised-13C pyruvate conversion to lactate (KpL), alanine (KpA), and bicarbonate (KpB) with reproducibility and satisfactory signal-to-noise ratio (8.2 ± 1.8×102 s−1, 2.3 ± 2.1×102 s−1 to 2.1 ± 1.3 x103 s−1, respectively; mean ± SD). Model predictions were in statistical agreement with the kinetic constants used in the simulations. Conclusion Our metabolic model could be used to measure metabolic conversion of hyperpolarised-13C metabolites in the context of surgery, where postoperative insulin resistance is well-known to be linked to stress-induced upregulation of pyruvate dehydrogenase inhibitor.

Effect of home-based heat therapy on skeletal muscle blood flow during exercise in older adults

The arterial vasculature undergoes profound changes across the lifespan. This vascular aging manifests as structural (e.g., vascular rarefaction) and functional (e.g., endothelial dysfunction) maladaptations. These age-related maladaptations contribute to the hypo-perfusion of skeletal muscle during conditions that require an elevated blood supply and substrate delivery (e.g., exercise) by tipping the vasoactive balance in favor of vasoconstriction. Acute heat exposure increases body and tissue temperature, increases blood flow and shear stress throughout the arterial tree, and initiates a humoral response. Importantly, chronic exposure to these temperature-dependent stimuli may reverse age-related vascular dysfunction, thereby improving perfusion of active skeletal muscle (i.e., exercise hyperemia). However, the effect of chronic heat therapy on exercise hyperemia has never been explored. Therefore, the purpose of this pilot study was to test the hypothesis that home-based heat therapy would increase skeletal muscle blood flow in older adults performing plantar flexion exercise. Six older adults (5 women; 67 ± 4 years) performed graded (5, 9, and 14 kg) unilateral dynamic plantar flexion exercise before (pre) and after (post) 8 weeks of home-based heat therapy. Each session of heat therapy required participants to immerse their lower legs ~33 cm into a heated (~ 42°C) and circulated water bath 4 days per week, for 45 min per session. Dynamic plantar flexion exercise was performed using a duty cycle of 1 s contraction and 2 s relaxation. Superficial femoral artery blood velocity and diameter were measured via Duplex ultrasonography and used to calculate the change in blood flow measured from baseline to each stage of exercise. Vascular conductance was calculated as flow/pressure. The change in leg blood flow during exercise was increased following heat therapy ( P = 0.08 for main effect of time), an effect that was mediated by augmented vascular conductance (5 kg: pre, Δ143 ± 89 ml/min/mmHg vs post, Δ188 ± 89 ml/min/mmHg; 9 kg: pre, Δ225 ± 89 ml/min/mmHg vs post, Δ234 ± 89 ml/min/mmHg; 14 kg: pre, Δ264 ± 89 ml/min/mmHg vs post, Δ290 ± 89 ml/min/mmHg; P = 0.07). Our preliminary data suggest that home-based heat therapy increases skeletal muscle blood flow during exercise in older adults, and may serve as a pragmatic intervention to improve exercise and functional capacity in this population. Supported by: American Heart Association TPA958179 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.