Muscle Oxygenation and Microvascular Reactivity Across Different Stages of CKD: A Near-Infrared Spectroscopy Study.

RATIONALE & OBJECTIVE: Previous studies in chronic kidney disease (CKD) showed that vascular dysfunction in different circulatory beds progressively deteriorates with worsening CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with different stages of CKD versus controls. STUDY DESIGN: Observational controlled study. SETTING & PARTICIPANTS: 90 participants (18 per CKD stage 2, 3a, 3b, and 4, as well as 18 controls). PREDICTOR: CKD stage. OUTCOME: The primary outcome was muscle oxygenation at rest. Secondary outcomes were muscle oxygenation during occlusion-reperfusion and exercise, and muscle microvascular reactivity (hyperemic response). ANALYTICAL APPROACH: Continuous measurement of muscle oxygenation [tissue saturation index (TSI)] using near-infrared spectroscopy at rest, during occlusion-reperfusion, and during a 3-minute handgrip exercise (at 35% of maximal voluntary contraction). Aortic pulse wave velocity and carotid intima-media thickness were also recorded. RESULTS: Resting muscle oxygenation did not differ across the study groups (controls: 64.3% ± 2.9%; CKD stage 2: 63.8% ± 4.2%; CKD stage 3a: 64.1% ± 4.1%; CKD stage 3b: 62.3% ± 3.3%; CKD stage 4: 62.7% ± 4.3%; P=0.6). During occlusion, no significant differences among groups were detected in the TSI occlusion magnitude and TSI occlusion slope. However, during reperfusion the maximum TSI value was significantly lower in groups of patients with more advanced CKD stages compared with controls, as was the hyperemic response (controls: 11.2%±3.7%; CKD stage 2: 8.3%±4.6%; CKD stage 3: 7.8%±5.5%; CKD stage 3b: 7.3%±4.4%; CKD stage 4: 7.2%±3.3%; P=0.04). During the handgrip exercise, the average decline in TSI was marginally lower in patients with CKD than controls, but no significant differences were detected across CKD stages. LIMITATIONS: Moderate sample size, cross-sectional evaluation. CONCLUSIONS: Although no differences were observed in muscle oxygenation at rest or during occlusion, the microvascular hyperemic response during reperfusion was significantly impaired in CKD and was most prominent in more advanced CKD stages. This impaired ability of microvasculature to respond to stimuli may be a crucial component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance. PLAIN-LANGUAGE SUMMARY: Previous studies in chronic kidney disease (CKD) have shown that vascular dysfunction in different circulatory beds progressively deteriorates with CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with nondialysis CKD versus controls, as well as across different CKD stages. It showed that the microvascular hyperemic response after an arterial occlusion was significantly impaired in CKD and was worst in patients with more advanced CKD. No significant differences were detected in skeletal muscle oxygenation or muscle oxidative capacity at rest or during the handgrip exercise when comparing patients with CKD with controls or comparing across CKD stages. The impaired ability of microvasculature to respond to stimuli may be a component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance.

Cerebral oxygenation during exercise deteriorates with advancing chronic kidney disease.

BACKGROUND: Cognitive impairment and exercise intolerance are common in chronic kidney disease (CKD). Cerebral perfusion and oxygenation play a major role in both cognitive function and exercise execution. This study aimed to examine cerebral oxygenation during a mild physical stress in patients at different CKD stages and controls without CKD. METHODS: Ninety participants (18 per CKD stage 2, 3a, 3b and 4 and 18 controls) underwent a 3-min intermittent handgrip exercise at 35% of their maximal voluntary contraction. During exercise, cerebral oxygenation [oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb) and total haemoglobin (tHb)] was assessed by near-infrared spectroscopy. Indices of microvascular (muscle hyperaemic response) and macrovascular function (carotid intima-media thickness and pulse wave velocity (PWV)) and cognitive and physical activity status were also evaluated. RESULTS: No differences in age, sex and body mass index were detected among groups. The mini-mental state examination score was significantly reduced with advancing CKD stages (controls: 29.2 ± 1.2, stage 2: 28.7 ± 1.0, stage 3a: 27.8 ± 1.9, stage 3b: 28.0 ± 1.8, stage 4: 27.6 ± 1.5; P = .019). Similar trends were observed for physical activity levels and handgrip strength. The average response in cerebral oxygenation (O2Hb) during exercise was lower with advancing CKD stages (controls: 2.50 ± 1.54, stage 2: 1.30 ± 1.05, stage 3a: 1.24 ± 0.93, stage 3b: 1.11 ± 0.89, stage 4: 0.97 ± 0.80 µmol/l; P < .001). The average tHb response (index of regional blood volume) showed a similar decreasing trend (P = .003); no differences in HHb among groups were detected. In univariate linear analysis, older age, lower estimated glomerular filtration rate (eGFR), Hb, microvascular hyperaemic response and increased PWV were associated with poor O2Hb response during exercise. In the multiple model, eGFR was the only parameter independently associated with the O2Hb response. CONCLUSIONS: Brain activation during a mild physical task appears to decrease with advancing CKD as suggested by the smaller increase in cerebral oxygenation. This may contribute to impaired cognitive function and reduced exercise tolerance with advancing CKD.

Depression in systemic lupus erythematosus: A manifestation of microcirculation dysfunction?

OBJECTIVES: Depression is highly prevalent among systemic lupus erythematosus (SLE) patients. Brain hypoperfusion in neuropsychiatric SLE patients might be associated with emotional difficulties. However, no previous study examined possible associations of depression with brain oxygenation during a mild physical stress in non-neuropsychiatric SLE patients. Our study aimed to identify possible differences in cerebral oxygenation during exercise in SLE patients with and without depressive symptoms using near-infrared spectroscopy (NIRS) and examine possible underlying mechanisms through evaluation of vascular cell adhesion molecule 1 (VCAM-1) levels. METHODS: SLE patients without a known neuropsychiatric history or treatment with antidepressants or antipsychotic drugs were enrolled. Participants were assigned into groups based on Beck's Depression Inventory I (BDI-I). Patients with BDI-I score ≥10 comprised the SLE-depression group and those with BDI-I score <9 the SLE-non-depression group. All participants underwent a protocol involving a seated rest, a 3-min handgrip exercise (at 30% of maximal strength), and a 3-min recovery. NIRS was used to monitor changes in cerebral oxygenated hemoglobin (O2Hb), deoxygenated (HHb), and total hemoglobin (tHb). VCAM-1 levels were measured in serum samples. RESULTS: Twenty-three patients were enrolled. During exercise, the SLE-depression group exhibited a significantly lower increase in cerebral O2Hb [(peak-O2Hb (p = 0.039); O2Hb-area under the curve, AUC, p = 0.027) vs. SLE-non-depression group. BDI-I score was inversely correlated with AUC (rho = -0.493, p = 0.017) and positively correlated with VCAM-1 levels (rho = 0.501, p = 0.034). CONCLUSION: This study suggests a possible association between emotional abnormalities and microvascular impairment (cerebral oxygenation and endothelial dysfunction) in SLE However, larger studies are needed to confirm these results.

Blunted cerebral oxygenation during exercise in systemic lupus erythematosus patients.

OBJECTIVES: Subclinical brain lesions have been reported in systemic lupus erythematosus (SLE) patients. Advanced neuroimaging techniques have revealed microstructural and microvascular alterations. Most studies examining structural or functional brain abnormalities were performed either at rest or during a mental task. Our study aimed to examine possible differences in cerebral oxygenation during exercise between SLE patients without known neuropsychiatric manifestations and age-matched controls, using near-infrared-spectroscopy (NIRS) and examine possible underlying mechanisms through evaluation of brain derived neurotrophic factor (BDNF) levels. METHODS: The protocol involved a seated rest, a 3-min submaximal (30%) handgrip exercise, and a 3-min recovery. Continuous-NIRS was used to monitor changes in cerebral-oxygenated (O2Hb), de-oxygenated (HHb) and total-haemoglobin (tHb). BDNF levels were measured in serum samples. RESULTS: Twenty-six SLE patients and 27 matched controls were enrolled. No differences were observed in baseline characteristics. During exercise, cerebral-O2Hb increased in both groups. However, SLE patients exhibited a significantly lower average- (1.20 ± 0.89 vs. 2.69 ± 2.46, p=0.001) and peak-O2Hb response (2.89 ± 1.56 vs. 5.83 ± 4.59, p=0.004) compared to controls. Serum BDNF levels were significantly lower in SLE patients compared to controls (p<0.01). CONCLUSIONS: To our knowledge, this is the first study to evaluate cerebral oxygenation during exercise using NIRS in SLE patients compared to age-matched controls. Our data show that SLE patients even without overt neuropsychiatric manifestations exhibit a blunted increase in cerebral-O2Hb during a submaximal exercise stimulus. Examining brain oxygenation during a simple exercise task may assist in identifying patients with early alterations in cerebral function.

Hemodialysis Effects on Autonomic Function: Results of Linear and Nonlinear Analysis of Heart Rate Variability at Rest and in Response to Physical and Mental Stress Tests.

INTRODUCTION: Cardiac arrhythmias are the most common cause of death in hemodialysis. Autonomic dysfunction plays a central role in this arrhythmogenic background. Previous studies on hemodialysis-related changes in heart rate variability (HRV) give contradictory results. This study investigated HRV indices both at rest and in response to physical and mental stimulation maneuvers at multiple time-points around and during the hemodialysis procedure. METHODS: Autonomic function was assessed by linear and nonlinear HRV indices at predialysis, during dialysis (3 equal time-periods), postdialysis, and on the nondialysis day in 36 hemodialysis patients. Continuous measurement of beat-by-beat heart rate was recorded with Finometer-PRO (The Netherlands) at rest and after orthostatic, sit-to-stand, handgrip, and mental-arithmetic test. RESULTS: The RMSSD, SD1, and SD2 indices significantly increased during dialysis (early-HD, mid-HD, late-HD periods) compared with the predialysis levels (p < 0.05) and returned to baseline postdialysis (RMSSD: 54.39 ± 83.73 vs. 137.98 ± 109.53* vs. 119.85 ± 97.34* vs. 144.47 ± 88.74* vs. 85.82 ± 121.43msec, *p < 0.05 vs. predialysis and postdialysis). No differences were detected in the above indices between the predialysis and nondialysis day. However, postdialysis, the HRV responses to orthostatic and sit-to-stand tests were more exaggerated than in the predialysis measurements (p < 0.05). The HRV responses both at resting and physical tests in the nondialysis day were similar to the predialysis levels. HRV indices in the mental arithmetic test during hemodialysis were much higher than at the nondialysis day (RMSSD: 77.05 [180.41] versus 19.75 [105.47] msec; p = 0.031). CONCLUSIONS: Hemodialysis causes marked changes in the autonomic function. Resting HRV indices return to baseline postdialysis, but HRV responses to physical stress remain exaggerated and return to baseline on the nondialysis day. Detecting patients with significant autonomic dysfunction may help towards reduction of arrhythmia risk through individualized approaches.

Muscle Oxygenation, Neural, and Cardiovascular Responses to Isometric and Workload-matched Dynamic Resistance Exercise.

Differences in blood flow patterns and energy cost between isometric and dynamic resistance exercise may result to variant cardiovascular, neural, and muscle metabolic responses. We aimed to compare the cardiovascular, baroreceptor sensitivity, and muscle oxygenation responses between workload-matched, large muscle-mass isometric and dynamic resistance exercises. Twenty-four young men performed an isometric and a dynamic double leg-press protocol (4 sets×2 min) with similar tension time index (workload). Beat-by-beat hemodynamics, baroreceptor sensitivity, muscle oxygenation, and blood lactate were assessed. The increase in blood pressure was greater (p<0.05) in the 1st set during dynamic than isometric exercise (by ~4.5 mmHg), not different in the 2nd and 3rd sets, and greater in the 4th set during isometric exercise (by ~5 mmHg). Dynamic resistance exercise evoked a greater increase in heart rate, stroke volume, cardiac output, and contractility index (p<0.05), and a greater decline in peripheral resistance, baroreceptor sensitivity, and cardiac function indices than isometric exercise (p<0.05). Participants exhibited a greater reduction in muscle oxyhemoglobin and a greater increase in muscle deoxyhemoglobin in dynamic versus isometric exercise (p<0.001-0.05), with no differences in total hemoglobin and blood lactate. In conclusion, large muscle-mass, multiple-set isometric exercise elicits a relatively similar blood pressure but blunted cardiovascular and baroreceptor sensitivity responses compared to workload-matched dynamic resistance exercise. Differences in blood pressure responses between protocols appear small (~5 mmHg) and are affected by the number of sets. The muscle oxidative stimulus is greater during dynamic resistance exercise than workload-matched isometric exercise.

Brain oxygenation during multiple sets of isometric and dynamic resistance exercise of equivalent workloads: Association with systemic haemodynamics.

Brain function relies on sufficient blood flow and oxygen supply. Changes in cerebral oxygenation during exercise have been linked to brain activity and central command. Isometric- and dynamic-resistance exercise-(RE) may elicit differential responses in systemic circulation, neural function and metabolism; all important regulators of cerebral circulation. We examined whether (i) cerebral oxygenation differs between isometric- and dynamic-RE of similar exercise characteristics and (ii) cerebral oxygenation changes relate to cardiovascular adjustments occurring during RE. Fourteen men performed, randomly, an isometric-RE and a dynamic-RE of similar characteristics (bilateral-leg-press, 2-min×4-sets, 30% of maximal-voluntary-contraction, equivalent tension-time-index/workload). Cerebral-oxygenation (oxyhaemoglobin-O2Hb; total haemoglobin-tHb/blood-volume-index; deoxyhemoglobin-HHb) was assessed by NIRS and beat-by-beat haemodynamics via photoplethysmography. Cerebral-O2Hb and tHb progressively increased from the 1st to 4th set in both RE-protocols (p < 0.05); HHb slightly decreased (p < 0.05). Changes in NIRS-parameters were similar between RE-protocols within each exercise-set (p = 0.91-1.00) and during the entire protocol (including resting-phases) (p = 0.48-0.63). O2Hb and tHb changes were not correlated with changes in systemic haemodynamics. In conclusion, cerebral oxygenation/blood-volume steadily increased during multiple-set RE-protocols. Isometric- and dynamic-RE of matched exercise characteristics resulted in similar prefrontal oxygenation/blood volume changes, suggesting similar cerebral haemodynamic and possibly neuronal responses to maintain a predetermined force.

Effects of Work and Recovery Duration and Their Ratio on Cardiorespiratory and Metabolic Responses During Aerobic Interval Exercise.

ABSTRACT: Myrkos, A, Smilios, I, Zafeiridis, A, Iliopoulos, S, Kokkinou, EM, Douda, H, and Tokmakidis, SP. Effects of work and recovery duration and their ratio on cardiorespiratory and metabolic responses during aerobic interval exercise. J Strength Cond Res 36(8): 2169-2175, 2022-This study examined the effect of work and recovery durations and of work-to-rest ratio (WRR) on total exercise time and oxygen consumption (V̇ o2 max), on exercise time above 80, 90, and 95% of V̇ o2 max and HRmax, and on blood lactate concentrations during aerobic interval exercise. Twelve men (22.1 ± 1 year) executed, until exhaustion, 4 interval protocols at an intensity corresponding to 100% of maximal aerobic velocity. Two protocols were performed with work bout duration of 120 seconds and recovery durations of 120 (WRR: 1:1) or 60 seconds (WRR: 2:1), and 2 protocols with work bout duration of 60 seconds and recovery durations of 60 (WRR: 1:1) or 30 seconds (WRR: 2:1). When compared at equal exercise time, total V̇ o2 and exercise time at V̇ o2 above 80, 90, and 95% of V̇ o2 max were longer ( p < 0.05) in 120:120, 120:60 and 60:30 vs. the 60:60 protocol. When analyzed for total exercise time (until exhaustion), total V̇ o2 was higher ( p < 0.01) in the 60:60 compared with all other protocols, and in the 120:120 compared with 120:60. Exercise time >95% of V̇ o2 max and HRmax was higher ( p < 0.05) in the 120:120 vs. the 60:60 protocol; there were no differences among protocols for exercise time >90% of V̇ o2 max and HRmax. Blood lactate was lower ( p < 0.05) in the 60:60 compared with all other protocols and in the 60:30 vs. the 120:60. In conclusion, when interval exercise protocols are executed at similar effort (until exhaustion), work and recovery durations do not, in general, affect exercise time at high oxygen consumption and HR rates. However, as work duration decreases, a higher work-to-recovery ratio (e.g., 2:1) should be used to achieve and maintain high (>95% of maximum) cardiorespiratory stimulus. Longer work bouts and higher work-to-recovery ratio seem to activate anaerobic glycolysis to a greater extent, as suggested by greater blood lactate concentrations.

Εndothelial and microvascular function in CKD: Evaluation methods and associations with outcomes.

BACKGROUND: Cardiovascular disease is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Endothelial dysfunction, the hallmark of atherosclerosis, is suggested to be involved pathogenetically in cardiovascular and renal disease progression in these patients. METHODS: This is a narrative review presenting the techniques and markers used for assessment of microvascular and endothelial function in patients with CKD and discussing findings of the relevant studies on the associations of endothelial dysfunction with co-morbid conditions and outcomes in this population. RESULTS: Venous Occlusion Plethysmography was the first method to evaluate microvascular function; subsequently, several relevant techniques have been developed and used in patients with CKD, including brachial Flow-Mediated Dilatation, and more recently, Near-Infrared Spectroscopy and Laser Speckle Contrast Analysis. Furthermore, several circulating biomarkers are commonly used in clinical research. Studies assessing endothelial function using the above techniques and biomarkers suggest that endothelial dysfunction occurs early in CKD and contributes to the target organ damage, cardiovascular events, death and progression towards end-stage kidney disease. CONCLUSIONS: Older and newer functional methods and several biomarkers have assessed endothelial dysfunction in CKD; accumulated evidence supports an association of endothelial dysfunction with outcomes. Future research with new, non-invasive and easily applicable methods could further delineate the role of endothelial dysfunction on cardiovascular and renal disease progression in patients with CKD.

Exertional Desaturation in Idiopathic Pulmonary Fibrosis: The Role of Oxygen Supplementation in Modifying Cerebral-Skeletal Muscle Oxygenation and Systemic Hemodynamics.

BACKGROUND: In patients with idiopathic pulmonary fibrosis (IPF) with isolated exertional desaturation, there are limited data regarding the effectiveness of oxygen supplementation during exercise training; the underlying mechanisms that contribute to these responses are unknown. OBJECTIVES: To examine in these IPF patients the effects of oxygen supplementation during submaximal exercise (vs. medical air) on cerebral/skeletal muscle oxygenation and systemic hemodynamics. METHODS: In this randomized, cross-over, placebo-controlled trial, IPF patients (n = 13; 63.4 ± 9.6 years) without resting hypoxemia but a significant desaturation during maximal cardiopulmonary exercise testing underwent 2 steady-state exercise trials (65% peak-work-load), breathing either oxygen-enriched or medical air. Cerebral/skeletal muscle oxygenation (near-infrared spectroscopy) and beat-by-beat hemodynamics (photoplethysmography) were monitored. RESULTS: In the air protocol, from the initial minutes of submaximal exercise, patients exhibited a marked decline in cerebral oxygenated hemoglobin (O2Hb) and an abrupt rise in deoxygenated hemoglobin (HHb). Oxygen supplementation alleviated desaturation, lessened dyspnea, and prolonged exercise duration (p < 0.01). Oxygen supplementation during exercise (i) attenuated cerebral deoxygenation (cerebral-HHb: 0.7 ± 1.9 vs. 2.5 ± 1.5 µmol/L, O2 and air protocol; p = 0.009) and prevented cerebral-Hbdifference decline (2.1 ± 2.7 vs. -1.7 ± 2.0 µmol/L; p = 0.001), (ii) lessened the decline in muscle O2-saturation index, and (iii) at isotime exercise, it resulted in lower muscle-HHb (p = 0.05) and less leg fatigue (p < 0.05). No differences between protocols were observed in exercise cardiac output and vascular resistance. CONCLUSIONS: IPF patients with isolated exertional hypoxemia exhibit an inability to increase/maintain cerebral oxygenation during submaximal exercise. Correcting desaturation with O2 supplementation prevented the decline in brain oxygenation, improved muscle oxygenation, and lessened dyspnea, suggesting an efficacy of acute oxygen supplementation during exercise training in protecting brain hypoxia in these IPF patients.

Cardiorespiratory fitness assessed by cardiopulmonary exercise testing between different stages of pre-dialysis chronic kidney disease: A systematic review and meta-analysis.

AIM: The burden of several cardiovascular risk factors increases in parallel to renal function decline. Exercise intolerance is common in patients with chronic kidney disease (CKD) and has been associated with increased risk of adverse outcomes. Whether indices of cardiorespiratory capacity deteriorate with advancing CKD stages is unknown. METHODS: We conducted a systematic review and meta-analysis of studies assessing cardiorespiratory capacity in adult patients with pre-dialysis CKD using cardiopulmonary exercise testing (CPET) and reporting data for different stages. Our primary outcome was differences in peak oxygen uptake (VO2 peak) between patients with CKD Stages 2-3a and those with Stages 3b-5(pre-dialysis). Literature search was undertaken in PubMed, Web of Science and Scopus databases, and abstract books of relevant meetings. Quality assessment was undertaken with Newcastle-Ottawa-Scale. RESULTS: From 4944 records initially retrieved, six studies with 512 participants fulfilling our inclusion criteria were included in the primary meta-analysis. Peak oxygen uptake (VO2 peak) was significantly higher in patients with CKD Stages 2-3a versus those with Stages 3b-5(pre-dialysis) [weighted-mean-difference, WMD: 2.46, 95% CI (1.15, 3.78)]. Oxygen consumption at ventilatory threshold (VO2 VT) was higher in Stages 2-3a compared with those in Stages 3b-5(pre-dialysis) [standardized-mean-difference, SMD: 0.59, 95% CI (0.06, 1.1)], while no differences were observed for maximum workload and respiratory-exchange-ratio. A secondary analysis comparing patients with CKD Stages 2-3b and Stages 4-5(pre-dialysis), yielded similar results [WMD: 1.78, 95% CI (1.34, 2.22)]. Sensitivity analysis confirmed the robustness of these findings. CONCLUSION: VO2 peak and VO2 VT assessed with CPET are significantly lower in patients in CKD Stages 3b-5 compared with Stages 2-3a. Reduced cardiorespiratory fitness may be another factor contributing to cardiovascular risk increase with advancing CKD.

Dietary nitrate improves muscle microvascular reactivity and lowers blood pressure at rest and during isometric exercise in untreated hypertensives.

OBJECTIVE: This double-blind, cross-over study examined in drug-naïve hypertensives the effects of a single dose of dietary nitrate (beetroot juice, BRJ) on (a) office/ambulatory BP and arterial stiffness, (b) muscle microvascular function, and (c) hemodynamic responses and cardiovagal baroreceptor sensitivity (cBRS) at rest and during isometric exercise. METHODS: Eighteen untreated hypertensives (44.0 ± 2.6 years) consumed randomly, a nitrate-rich (8.1 mmol-BRJnitrate ) and a nitrate-depleted (BRJplacebo ) BRJ. Office BP and pulse wave velocity were assessed before/after BRJ. An occlusion-reperfusion maneuver with continuous monitoring of muscle oxygenated hemoglobin (O2 Hb) and total hemoglobin (tHb), via NIRS, followed. Participants performed submaximal isometric handgrip with beat-by-beat monitoring of hemodynamics and cBRS. Ambulatory BP assessment followed. RESULTS: During reperfusion, following arterial occlusion, the magnitude and rate of muscle microvascular reoxygenation (O2 Hb) and red blood cell content (tHb) were higher in BRJnitrate vs BRJplacebo (P < 0.05), suggesting improved microvascular reactivity. Office/ambulatory BP were lower following BRJnitrate vs BRJplacebo (P < 0.05); pulse-wave-velocity was not altered. During isometric handgrip, BP and peripheral resistance rise were smaller in BRJnitrate vs BRJplacebo (P < 0.01-0.05), with no differences in cBRS. CONCLUSIONS: In drug-naïve hypertensives, a single dose of BRJ induces (a) short-term reductions in resting/ambulatory BP, (b) acute improvements in muscle microvascular function, and (c) attenuation in BP and peripheral resistance responses during isometric exercise.

Beetroot Increases Muscle Performance and Oxygenation During Sustained Isometric Exercise, but Does Not Alter Muscle Oxidative Efficiency and Microvascular Reactivity at Rest.

OBJECTIVE: To examine the effects of beetroot juice (BRJ) on (i) in vivo skeletal muscle O2 consumption (mVO2) and microvascular reactivity at rest and (ii) muscle performance, muscle oxygenation, and mVO2 during sustained isometric handgrip exercise (IHG). METHODS: Sixteen young males consumed, randomly, a nitrate-rich (8.1 mmol BRJnitrate) or nitrate-depleted (BRJplacebo) BRJ. After 2.5 hours, they performed an occlusion-reperfusion maneuver at rest, a 3-minute sustained IHG, and a sustained IHG to exhaustion with arterial occlusion. Changes in muscle oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), microvascular red blood cell content (tHb), and mVO2 were measured using near-infrared spectroscopy. Force output was recorded. RESULTS: During occlusion, the O2Hb decline did not differ between BRJnitrate and BRJplacebo (magnitude: -30.3 ± 1.6 vs. -31.1 ± 1.5 ΔµΜ; slope: -0.107 ± 0.007 vs. -0.111 ± 0.007 µΜ second-1). During reperfusion, all microvascular reactivity indices were not altered after BRJnitrate (e.g., O2Hbslope: 1.584 ± 0.093 vs. 1.556 ± 0.072 µΜ second-1). During the second and third minute of IHG, O2Hb and tHb were higher in BRJnitrate versus BRJplacebo (p < 0.05), and force output was higher during the third minute (10.8 ± 0.7 vs. 9.5 ± 1.2 kg; p < 0.05); HHb did not differ between trials. In IHG with arterial occlusion, BRJnitrate prolonged the time to fatigue (94.1 ± 5.8 vs. 80.1 ± 3.3 seconds; p < 0.01), with no effects on O2Hb decline (O2Hbslope: -0.226 ± 0.015 vs. -0.230 ± 0.026 µΜ s-1) and mVO2 (14.1 ± 1.0 vs. 14.3 ± 1.6 µmol l-1 minute-1). CONCLUSION: Acute BRJ ingestion in moderately trained individuals (i) did not alter in vivo skeletal muscle microvascular reactivity (index of microvascular function at rest) and basal oxidative efficiency, (ii) increased muscle oxygenation during IHG (possibly via enhanced O2 delivery), and (iii) provided ergogenic benefits during sustained IHG with no effects on muscle oxidative efficiency. The ergogenic effects of BRJ appeared independent of its tissue perfusion benefits.

The Effects of Recovery Duration During High-Intensity Interval Exercise on Time Spent at High Rates of Oxygen Consumption, Oxygen Kinetics, and Blood Lactate.

Smilios, I, Myrkos, A, Zafeiridis, A, Toubekis, A, Spassis, A, and Tokmakidis, SP. The effects of recovery duration during high-intensity interval exercise on time spent at high rates of oxygen consumption, oxygen kinetics, and blood lactate. J Strength Cond Res 32(8): 2183-2189, 2018-The recovery duration and the work-to-recovery ratio are important aspects to consider when designing a high-intensity aerobic interval exercise (HIIE). This study examined the effects of recovery duration on total exercise time performed above 80, 90, and 95% of maximum oxygen consumption (V[Combining Dot Above]O2max) and heart rate (HRmax) during a single-bout HIIE. We also evaluated the effects on V[Combining Dot Above]O2 and HR kinetics, blood lactate concentration, and rating of perceived exertion (RPE). Eleven moderately trained men (22.1 ± 1 year) executed, on 3 separate sessions, 4 × 4-minute runs at 90% of maximal aerobic velocity (MAV) with 2, 3, and 4 minutes of active recovery. Recovery duration did not affect the percentage of V[Combining Dot Above]O2max attained and the total exercise time above 80, 90, and 95% of V[Combining Dot Above]O2max. Exercise time above 80 and 90% of HRmax was longer with 2 and 3 minutes (p ≤ 0.05) as compared with the 4-minute recovery. Oxygen uptake and HR amplitude were lower, mean response time slower (p ≤ 0.05), and blood lactate and RPE higher with 2 minutes compared with 4-minute recovery (p ≤ 0.05). In conclusion, aerobic metabolism attains its upper functional limits with either 2, or 3 or 4 minutes of recovery during the 4 × 4-minute HIIE; thus, all rest durations could be used for the enhancement of aerobic capacity in sports, fitness, and clinical settings. The short (2 minutes) compared with longer (4 minutes) recovery, however, evokes greater cardiovascular and metabolic stress and activates to a greater extent anaerobic glycolysis and hence, could be used by athletes to induce greater overall physiological challenge.

Impairments in microvascular function and skeletal muscle oxygenation in women with gestational diabetes mellitus: links to cardiovascular disease risk factors.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a risk factor for the development of endothelial dysfunction and cardiovascular disease. However, in vivo microvascular endothelial function in GDM has not been investigated. This study aimed to examine, using near-infrared spectroscopy (NIRS), whether: (1) there are differences in microvascular reactivity and skeletal muscle oxygen consumption (m[Formula: see text]) at rest and during exercise between GDM and uncomplicated pregnancies; and (2) there is an association of NIRS indices with macrovascular function and cardiovascular disease risk factors. METHODS: Twenty-nine pregnant women (13 with GDM and 16 women with uncomplicated pregnancy, 28 ± 2 gestational weeks) underwent arterial stiffness (pulse wave velocity [PWV]) and 24 h ambulatory BP (24 h BP) evaluation. NIRS continuously monitored, non-invasively, changes in muscle oxygenated and deoxygenated haemoglobin and tissue O2 saturation index (TSI, %) during arterial occlusion/reperfusion and intermittent handgrip exercise. m[Formula: see text] and vascular reactivity indices were calculated. RESULTS: During occlusion and reperfusion, women with GDM exhibited slower TSI response (occlusion slope: -0.06 ± 0.02 vs -0.10 ± 0.04, in GDM and controls, respectively; reperfusion slope: 0.65 ± 0.26 vs 1.05 ± 0.41, respectively), lower m[Formula: see text] (1.3 ± 1.2 vs 3.8 ± 2.3 µmol l-1 min-1) and blunted hyperaemia (ΔTSI 6.8 ± 2.9 vs 9.5 ± 3.4) compared with controls (p < 0.01). Despite similar handgrip strength in the GDM and control groups (29.1 ± 8.1 vs 26.2 ± 10.4 kg, respectively), during repeated forearm contractions, women with GDM presented a blunted TSI response (6.5 ± 3.9 vs 19.2 ± 10.9; p < 0.01) and a reduced capacity to maintain the predetermined handgrip (23.4 ± 2.9 vs 27.4 ± 3.8%, p < 0.05). NIRS indices correlated with PWV, 24 h BP and blood glucose concentration earlier in pregnancy (r = 0.40-0.60; p < 0.05). CONCLUSIONS/INTERPRETATION: Women with GDM exhibited a characteristic blunted TSI curve, showing alterations in muscle oxygenation and microvascular responsiveness compared with women with uncomplicated pregnancies. These alterations were manifested during exercise and possibly contribute to the reduced exercise tolerance in GDM. NIRS indices correlated with macrovascular indices (arterial stiffness) and 24 h BP.

Anterior cruciate ligament deficiency reduces walking economy in "copers" and "non-copers".

PURPOSE: Patients with ACL injury requiring surgical treatment (non-copers) demonstrate altered neuromuscular control and gait pattern compared with those returning to their pre-injury activities without surgery (copers). Pathological gait pattern may increase the energy cost of walking. We compared the energy cost of flat, uphill, and downhill walking between ACL-deficient and healthy individuals and between "copers" and "non-copers". METHODS: Nineteen young males with unilateral ACL injury were allocated into "copers" and "non-copers" according to their ability to return to pre-injury activity without ACL reconstruction. Lysholm and IKDC scales were recorded, and a control group (n = 10) matched for physical characteristics and activity levels was included. All participants performed 8-min walking tasks at 0, +10, and -10 % gradients. Energy cost was assessed by measurement of oxygen consumption (VO2). HR and ventilation (VE), respiratory exchange ratio (RER), and VE/VO2 were also measured. RESULTS: VO2 and HR were higher in ACL-deficient patients than in controls during walking at 0, +10, and -10 % gradients (p < 0.01-0.05). There were no differences between "copers" and "non-copers" in VO2 and HR for any gradient. No differences were observed in VE, RER, and VE/VO2 among the three groups. CONCLUSIONS: The walking economy of level, uphill, and downhill walking is reduced in ACL-deficient patients. Despite the improved functional and clinical outcome of "copers", their walking economy appears similar to that of "non-copers" but impaired compared with healthy individuals. The higher energy demand and effort during locomotion in "copers" and "non-copers" has clinical implications for designing safer rehabilitation programmes. The increased energy cost in "copers" may be another parameter to consider when deciding on the most appropriate therapeutic intervention (operative and non-operative), particularly for athletes. LEVEL OF EVIDENCE: II.

Anatomic single-bundle anterior cruciate ligament reconstruction improves walking economy: hamstrings tendon versus patellar tendon grafts.

PURPOSE: Anterior cruciate ligament (ACL) injury is associated with a pathologic gait pattern and increased energy cost during locomotion. ACL reconstruction could improve the gait pattern. Hamstrings tendon (HAM) and bone-patellar tendon-bone (BPTB) grafts are usually used for reconstruction. The aim of this study was to compare the efficacy of anatomic ACL reconstruction with HAM and BPTB grafts on improving and normalizing the energy cost and physiologic reserves during flat, uphill, and downhill walking. METHODS: Twenty male subjects with unilateral ACL injuries were randomly assigned to ACL reconstruction with a HAM (n = 10) or BPTB (n = 10) graft. Ten matched controls were also enrolled. All participants performed three 8-min walking tasks at 0, +10, and -10 % gradients before and 9 months after surgery. Energy cost (oxygen consumption, VO2), heart rate (HR), and ventilation (VE) were measured. Lysholm/IKDC scores were recorded. RESULTS: Pre-operatively, VO2, HR, and VE were higher in the HAM and BPTB groups than in controls during walking at 0, +10, and -10 % gradients (p < 0.001-0.01). Post-operatively, both HAM and BPTB groups showed reduced VO2, HR, and VE during the three walking tasks (p < 0.001-0.01). Although the post-operative VO2 in both surgical groups reached 90-95 % of the normative (control) value during walking, it remained elevated against the value observed in controls (p < 0.001-0.01). The HAM and BPTB groups showed no differences in post-surgical VO2 or HR during walking at all three gradients. CONCLUSION: Anatomic ACL reconstruction with either HAM or BPTB graft resulted in similar short-term improvements in energy cost and nearly normalized locomotion economy and cardiorespiratory reserves during flat, uphill, and downhill walking. The improved locomotion economy is an additional benefit of anatomic ACL reconstruction, irrespective of the type of graft used, that the orthopaedic surgeons should consider. LEVEL OF EVIDENCE: II.

Static and Dynamic Handgrip Strength Endurance: Test-Retest Reproducibility.

PURPOSE: This study investigated the reliability of static and dynamic handgrip strength endurance using different protocols and indicators for the assessment of strength endurance. METHODS: Forty young, healthy men and women (age, 18-22 years) performed 2 handgrip strength endurance protocols: a static protocol (sustained submaximal contraction at 50% of maximal voluntary contraction) and a dynamic one (8, 10, and 12 maximal repetitions). The participants executed each protocol twice to assess the test-retest reproducibility. Total work and total time were used as indicators of strength endurance in the static protocol; the strength recorded at each maximal repetition, the percentage change, and fatigue index were used as indicators of strength endurance in the dynamic protocol. RESULTS: The static protocol showed high reliability irrespective of sex and hand for total time and work. The 12-repetition dynamic protocol exhibited moderate-high reliability for repeated maximal repetitions and percentage change; the 8- and 10-repetition protocols demonstrated lower reliability irrespective of sex and hand. The fatigue index was not a reliable indicator for the assessment of dynamic handgrip endurance. CONCLUSIONS: Static handgrip endurance can be measured reliably using the total time and total work as indicators of strength endurance. For the evaluation of dynamic handgrip endurance, the 12-repetition protocol is recommended, using the repeated maximal repetitions and percentage change as indicators of strength endurance. CLINICAL RELEVANCE: Practitioners should consider the static (50% maximal voluntary contraction) and dynamic (12 repeated maximal repetitions) protocols as reliable for the assessment of handgrip strength endurance. The evaluation of static endurance in conjunction with dynamic endurance would provide more complete information about hand function.

Global Metabolic Stress of Isoeffort Continuous and High Intensity Interval Aerobic Exercise: A Comparative 1H NMR Metabonomic Study.

The overall metabolic/energetic stress that occurs during an acute bout of exercise is proposed to be the main driving force for long-term training adaptations. Continuous and high-intensity interval exercise protocols (HIIE) are currently prescribed to acquire the muscular and metabolic benefits of aerobic training. We applied 1H NMR-based metabonomics to compare the overall metabolic perturbation and activation of individual bioenergetic pathways of three popular aerobic exercises matched for effort/strain. Nine men performed continuous, long-interval (3 min), and short-interval (30 s) bouts of exercise under isoeffort conditions. Blood was collected before and after exercise. The multivariate PCA and OPLS-DA models showed a distinct separation of pre- and postexercise samples in three protocols. The two models did not discriminate the postexercise overall metabolic profiles of the three exercise types. Analysis focused on muscle bioenergetic pathways revealed an extensive upregulation of carbohydrate-lipid metabolism and the TCA cycle in all three protocols; there were only a few differences among protocols in the postexercise abundance of molecules when long-interval bouts were performed. In conclusion, continuous and HIIE exercise protocols, when performed with similar effort/strain, induce comparable global metabolic response/stress despite their marked differences in work-bout intensities. This study highlights the importance of NMR metabonomics in comprehensive monitoring of metabolic consequences of exercise training in the blood of athletes and exercising individuals.

Exaggerated haemodynamic and neural responses to involuntary contractions induced by whole-body vibration in normotensive obese versus lean women.

What is the central question of this study? In obesity, the exaggerated blood pressure response to voluntary exercise is linked to hypertension, yet the mechanisms are not fully elucidated. We examined whether involuntary contractions elicit greater haemodynamic responses and altered neural control of blood pressure in normotensive obese versus lean women. What is the main finding and its importance? During involuntary contractions induced by whole-body vibration, there were augmented blood pressure and spontaneous baroreflex responses in obese compared with lean women. This finding is suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity. Passive contractions did not elicit differential heart rate responses in obese compared with lean women, implying other mechanisms for the blunted heart rate response reported during voluntary exercise in obesity. In obesity, the exaggerated blood pressure (BP) response to exercise is linked to hypertension, yet the mechanisms are not fully elucidated. In this study, we examined whether involuntary mechanical oscillations, induced by whole-body vibration (WBV), elicit greater haemodynamic responses and altered neural control of BP in obese versus lean women. Twenty-two normotensive, premenopausal women (12 lean and 10 obese) randomly underwent a passive WBV (25 Hz) and a control protocol (similar posture without WVB). Beat-by-beat BP, heart rate, stroke volume, systemic vascular resistance, cardiac output, parasympathetic output (evaluated by heart rate variability) and spontaneous baroreceptor sensitivity (sBRS) were assessed. We found that during WBV, obese women exhibited an augmented systolic BP response compared with lean women that was correlated with body fat percentage (r = 0.77; P < 0.05). The exaggerated BP rise was driven mainly by the greater increase in cardiac output index in obese versus lean women, associated with a greater stroke volume index in obese women. Involuntary contractions did not elicit a differential magnitude of responses in heart rate, heart rate variability indices and systemic vascular resistance in obese versus lean women; however, they did result in greater sBRS responses (P < 0.05) in obese women. In conclusion, involuntary contractions elicited an augmented BP and sBRS response in normotensive obese versus lean women. The greater elevations in circulatory haemodynamics in obese women are suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity.