Jesse C. Craig

Influence of blood flow occlusion on the development of peripheral and central fatigue during small muscle mass handgrip exercise

Critical power represents an important threshold for neuromuscular fatigue development and may, therefore, dictate intensities for which exercise tolerance is determined by the magnitude of fatigue accrued. Peripheral fatigue appears to be constant across O2 delivery conditions for large muscle mass exercise, but this consistency is equivocal for smaller muscle mass exercise. We sought to determine the influence of blood flow occlusion during handgrip exercise on neuromuscular fatigue development and to examine the relationship between neuromuscular fatigue development and W ′. Blood flow occlusion influenced the development of both peripheral and central fatigue, thus providing further evidence that the magnitude of peripheral fatigue is not constant across O2 delivery conditions for small muscle mass exercise. W ′ appears to be related to the magnitude of fatigue accrued during exercise, which may explain the reported consistency of intramuscular metabolic perturbations and work performed for severe‐intensity exercise.

Dietary nitrate supplementation: impact on skeletal muscle vascular control in exercising rats with chronic heart failure

Chronic heart failure (CHF) results in central and peripheral derangements that ultimately reduce skeletal muscle O2 delivery and impair exercise tolerance. Dietary nitrate (NO3 (-)) supplementation improves skeletal muscle vascular function and tolerance to exercise. We tested the hypothesis that NO3 (-) supplementation would elevate exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats. Myocardial infarction (MI) was induced (coronary artery ligation) in young adult male rats. After 21 days of recovery, rats randomly received 5 days of NO3 (-)-rich beetroot juice (CHF + BR, n = 10) or a placebo (CHF, n = 10). Mean arterial pressure (carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) were measured during treadmill exercise (20 m/min, 5% grade). CHF-induced dysfunction, as determined by myocardial infarction size (29 ± 3% and 33 ± 4% in CHF and CHF + BR, respectively) and left ventricular end-diastolic pressure (18 ± 2 and 18 ± 2 mmHg in CHF and CHF + BR, respectively), and exercising mean arterial pressure (131 ± 3 and 128 ± 4 mmHg in CHF and CHF + BR, respectively) were not different (P > 0.05) between groups. Total exercising hindlimb skeletal muscle BF (95 ± 5 and 116 ± 9 ml·min(-1)·100 g(-1) in CHF and CHF + BR, respectively) and VC (0.75 ± 0.05 and 0.90 ± 0.05 ml·min(-1)·100 g(-1)·mmHg(-1) in CHF and CHF + BR, respectively) were 22% and 20% greater in BR-supplemented rats, respectively (P < 0.05). During exercise, BF in 9 and VC in 10 hindlimb muscles and muscle portions were significantly greater in the CHF + BR group. These results provide strong evidence that dietary NO3 (-) supplementation improves skeletal muscle vascular function during exercise in rats with CHF and, thus, support the use of BR as a novel therapeutic modality for the treatment of CHF.

The relationship between critical speed and the respiratory compensation point: Coincidence or equivalence.

Abstract It has previously been suggested that the respiratory compensation point (RCP) and critical speed (CS) parameters are equivalent and, therefore, like CS, RCP demarcates the boundary between the heavy- and severe-intensity domains. However, these findings are equivocal and therefore must be interpreted cautiously. Thus, we examined the relationship between CS and RCP across a wide range of subject fitness levels, in an attempt to determine if CS and RCP are equivalent. Forty men and 30 women (age: 23.2 ± 2.5 year, height: 174 ± 10 cm, body mass: 74.1 ± 15.7 kg) completed an incremental and four constant-speed protocols on a treadmill. RCP was determined as the point at which the minute ventilation increased disproportionately to CO2 production and the end-tidal CO2 partial pressure began to decrease. CS was determined from the constant-speed protocols using the linearized 1·time−1 model. CS and RCP, expressed as speed or metabolic rate, were not significantly different (11.7 ± 2.3 km·h−1 vs. 11.5 ± 2.3 km·h−1, p = 0.208; 2.88 ± 0.80 l·min−1 vs. 2.83 ± 0.72 l·min−1, p = 0.293) and were significantly correlated (r2 = 0.52, p < 0.0001; r2 = 0.74, p < 0.0001, respectively). However, there was a high degree of variability between the parameters. The findings of the current study indicate that, while on average CS and RCP were not different, the high degree of variability between these parameters does not permit accurate estimation of one from the other variable and suggests that these parameters may not be physiologically equivalent.

Effect of sodium nitrite on local control of contracting skeletal muscle microvascular oxygen pressure in healthy rats.

Exercise intolerance characteristic of diseases such as chronic heart failure (CHF) and diabetes is associated with reduced nitric oxide (NO) bioavailability from nitric oxide synthase (NOS), resulting in an impaired microvascular O2 driving pressure (Po2mv; O2 delivery/O2 utilization) and metabolic control. Infusions of the potent NO donor sodium nitroprusside augment NO bioavailability yet decrease mean arterial pressure (MAP) thereby reducing its potential efficacy for patient populations. To eliminate or reduce hypotensive sequelae, [Formula: see text] was superfused onto the spinotrapezius muscle. It was hypothesized that local [Formula: see text] administration would elevate resting Po2mv and slow Po2mv kinetics [increased time constant (τ) and mean response time (MRT)] following the onset of muscle contractions without decreasing MAP. In 12 anesthetized male Sprague-Dawley rats, Po2mv of the circulation-intact spinotrapezius muscle was measured by phosphorescence quenching during 180 s of electrically induced twitch contractions (1 Hz) before and after superfusion of sodium nitrite (NaNO2 30 mM). [Formula: see text] superfusion elevated resting Po2mv (control: 28.4 ± 1.1 vs. [Formula: see text]: 31.6 ± 1.2 mmHg; P ≤ 0.05), τ (control: 12.3 ± 1.2 vs. [Formula: see text]: 19.7 ± 2.2 s; P ≤ 0.05), and MRT (control: 19.3 ± 1.9 vs. [Formula: see text]: 25.6 ± 3.3 s; P ≤ 0.05). Importantly, these effects occurred in the absence of any reduction in MAP (103 ± 4 vs. 105 ± 4 mmHg, pre- and postsuperfusion respectively; P > 0.05). These results indicate that [Formula: see text] supplementation delivered to the muscle directly through [Formula: see text] superfusion enhances the blood-myocyte oxygen driving pressure without compromising MAP at rest and following the onset of muscle contraction. This strategy has substantial clinical utility for a range of ischemic conditions. NEW & NOTEWORTHY Ischemic conditions as diverse as chronic heart failure (CHF) and frostbite inflict tissue damage via inadequate O2 delivery. Herein we demonstrate that direct application of sodium nitrite enhances the O2 supply-O2 demand relationship, raising microvascular O2 pressure in healthy skeletal muscle. This therapeutic action of nitrite-derived nitric oxide occurred without inducing systemic hypotension and has the potential to relieve focal ischemia and preserve tissue vitality by enhancing O2 delivery.

Skeletal muscle microvascular and interstitial from rest to contractions

Oxygen pressure gradients across the microvascular walls are essential for oxygen diffusion from blood to tissue cells. At any given flux, the magnitude of these transmural gradients is proportional to the local resistance. The greatest resistance to oxygen transport into skeletal muscle is considered to reside in the short distance between red blood cells and myocytes. Although crucial to oxygen transport, little is known about transmural pressure gradients within skeletal muscle during contractions. We evaluated oxygen pressures within both the skeletal muscle microvascular and interstitial spaces to determine transmural gradients during the rest–contraction transient in anaesthetized rats. The significant transmural gradient observed at rest was sustained during submaximal muscle contractions. Our findings support that the blood–myocyte interface provides substantial resistance to oxygen diffusion at rest and during contractions and suggest that modulations in microvascular haemodynamics and red blood cell distribution constitute primary mechanisms driving increased transmural oxygen flux with contractions.

Vascular KATP channels mitigate severe muscle O2 delivery-utilization mismatch during contractions in chronic heart failure rats.

The vascular ATP-sensitive K+ (KATP) channel is a mediator of skeletal muscle microvascular oxygenation (PO2mv) during contractions in health. We tested the hypothesis that KATP channel function is preserved in chronic heart failure (CHF) and therefore its inhibition would reduce PO2mv and exacerbate the time taken to reach the PO2mv steady-state during contractions of the spinotrapezius muscle. Moreover, we hypothesized that subsequent KATP channel activation would oppose the effects of this inhibition. Muscle PO2mv (phosphorescence quenching) was measured during 180s of 1-Hz twitch contractions (∼6V) under control, glibenclamide (GLI, KATP channel antagonist; 5mg/kg) and pinacidil (PIN, KATP channel agonist; 5mg/kg) conditions in 16 male Sprague-Dawley rats with CHF induced via myocardial infarction (coronary artery ligation, left ventricular end-diastolic pressure: 18±1mmHg). GLI reduced baseline PO2mv (control: 28.3±0.9, GLI: 24.8±1.0mmHg, p<0.05), lowered mean PO2mv (average PO2mv during the overall time taken to reach the steady-state; control: 20.6±0.6, GLI: 17.6±0.3mmHg, p<0.05), and slowed the attainment of steady-state PO2mv (overall mean response time; control: 66.1±10.2, GLI: 93.6±7.8s, p<0.05). PIN opposed these effects on the baseline PO2mv, mean PO2mv and time to reach the steady-state PO2mv (p<0.05 for all vs. GLI). Inhibition of KATP channels exacerbates the transient mismatch between muscle O2 delivery and utilization in CHF rats and this effect is opposed by PIN. These data reveal that the KATP channel constitutes one of the select few well-preserved mechanisms of skeletal muscle microvascular oxygenation control in CHF.

Dynamics of middle cerebral artery blood flow velocity during moderate-intensity exercise

The dynamic response to a stimulus such as exercise can reveal valuable insights into systems control in health and disease that are not evident from the steady-state perturbation. However, the dynamic response profile and kinetics of cerebrovascular function have not been determined to date. We tested the hypotheses that bilateral middle cerebral artery blood flow mean velocity (MCAV) increases exponentially following the onset of moderate-intensity exercise in 10 healthy young subjects. The MCAV response profiles were well fit to a delay (TD) + exponential (time constant, τ) model with substantial agreement for baseline [left (L): 69, right (R): 64 cm/s, coefficient of variation (CV) 11%], response amplitude (L: 16, R: 13 cm/s, CV 23%), TD (L: 54, R: 52 s, CV 9%), τ (L: 30, R: 30 s, CV 22%), and mean response time (MRT) (L: 83, R: 82 s, CV 8%) between left and right MCAV as supported by the high correlations (e.g., MRT r = 0.82, P < 0.05) and low CVs. Test-retest reliability was high with CVs for the baseline, amplitude, and MRT of 3, 14, and 12%, respectively. These responses contrasted markedly with those of three healthy older subjects in whom the MCAV baseline and exercise response amplitude were far lower and the kinetics slowed. A single older stroke patient showed baseline ipsilateral MCAV that was lower still and devoid of any exercise response whatsoever. We conclude that kinetics analysis of MCAV during exercise has significant potential to unveil novel aspects of cerebrovascular function in health and disease.NEW & NOTEWORTHY Resolution of the dynamic stimulus-response profile provides a greater understanding of the underlying the physiological control processes than steady-state measurements alone. We report a novel method of measuring cerebrovascular blood velocity (MCAv) kinetics under ecologically valid conditions from rest to moderate-intensity exercise. This technique reveals that brain blood flow increases exponentially following the onset of exercise with 1) a strong bilateral coherence in young healthy individuals, and 2) a potential for unique age- and disease-specific profiles.

W′ expenditure and reconstitution during severe intensity constant power exercise: mechanistic insight into the determinants of W′

The sustainable duration of severe intensity exercise is well‐predicted by critical power (CP) and the curvature constant (W′). The development of the W′BAL model allows for the pattern of W′ expenditure and reconstitution to be characterized and this model has been applied to intermittent exercise protocols. The purpose of this investigation was to assess the influence of relaxation phase duration and exercise intensity on W′ reconstitution during dynamic constant power severe intensity exercise. Six men (24.6 ± 0.9 years, height: 173.5 ± 1.9 cm, body mass: 78.9 ± 5.6 kg) performed severe intensity dynamic handgrip exercise to task failure using 50% and 20% duty cycles. The W′BAL model was fit to each exercise test and the time constant for W′ reconstitution (τW′) was determined. The τW′ was significantly longer for the 50% duty cycle (1640 ± 262 sec) than the 20% duty cycle (863 ± 84 sec, P = 0.02). Additionally, the relationship between τW′ and CP was well described as an exponential decay (r2 = 0.90, P < 0.0001). In conclusion, the W′BAL model is able to characterize the expenditure and reconstitution of W′ across the contraction–relaxation cycles comprising severe intensity constant power handgrip exercise. Moreover, the reconstitution of W′ during constant power severe intensity exercise is influenced by the relative exercise intensity, the duration of relaxation between contractions, and CP.

Considerations for Identifying the Boundaries of Sustainable Performance.

We applaud Keir et al. (4) for their undertaking of a thorough study that investigated the association between several physiological phenomena and the threshold of sustainable exercise (i.e., critical power (CP)). This demarcation of sustainable exercise holds critical significance to applied and clinical exercise physiology, and the conclusion of the authors that several physiological phenomena coincide with CP is tempting but dangerous because of possible misinterpretation and overstatement of association between these phenomena. The authors leave the reader with the impression that their findings are the last, final word on the association among these various responses. It is unfortunate that the authors did disservice to the readership of the journal by ignoring recent work that contradicts the authors_ conclusion that all of these responses occur at the same V̇O2, suggesting these are ‘‘equivalent’’ and ‘‘interchangeable’’ phenomena. Consistent with previous findings, the current study demonstrated no significant differences between the means of these physiological phenomena when expressed as metabolic rates. However, it should not be lost that a lack of significant difference does not necessitate equivalence. It is paramount to consider the high degree of intrasubject variability and lack of universal expression, which preclude the ‘‘interchangeability’’ of these phenomena within a given subject (1–3). Moreover, a clear temporal separation among these phenomena suggests a sequence or cascade rather than a single event (1). These overlooked results highlight the likelihood of distinct physiological mechanisms that determine these phenomena and warrant consideration when interpreting the results of the current study. The authors acknowledged the observational nature of the current study but frequently alluded to equivalent determining mechanisms of these phenomena. Awareness must be raised with regard to the physiological interpretation of these data. Without rigorous investigation of the mechanisms underlying these phenomena or attempting to dissociate these parameters, one must take care to not overstate the ‘‘equivalence’’ and ‘‘interchangeability’’ of these phenomena. Thus, we believe that the association of the phenomena that occur in the metabolic and work rate region of CP is not settled but must await future investigations that seek to mechanistically link or uncouple these phenomena.

Effect of adipose tissue thickness, muscle site, and sex on near-infrared spectroscopy derived total-[hemoglobin + myoglobin]

Craig JC, Broxterman RM, Wilcox SL, Chen C, Barstow TJ. Effect of adipose tissue thickness, muscle site, and sex on near-infrared spectroscopy derived total-[hemoglobin + myoglobin]. J Appl Physiol 123: 1571-1578, 2017. First published September 21, 2017; doi: 10.1152/japplphysiol.00207.2017 .-Adipose tissue thickness (ATT) attenuates signals from near-infrared spectroscopy (NIRS) and diminishes the absolute quantification of underlying tissues by contemporary NIRS devices. Based on the relationship between NIRS-derived total-[hemoglobin + myoglobin] (total-[Hb + Mb]) and ATT, we tested the hypotheses that the correction factor for ATT 1) is muscle site specific; 2) does not differ between men and women; and that 3) exclusion of the shortest source-detector distance from data analysis increases total-[Hb + Mb]. Fourteen healthy subjects (7 men) rested in a neutral body position (supine or prone) while measurements of total-[Hb + Mb] and ATT were taken at four muscles common to resting and exercise studies: vastus lateralis (VL), rectus femoris (RF), gastrocnemius (GS), and flexor digitorum superficialis (FDS). ATT averaged 6.0 ± 0.4 mm across all muscles. Every muscle showed a negative slope ( r2: 0.6-0.94; P < 0.01) for total-[Hb + Mb] as a function of ATT: VL (-34 μM/mm), RF (-26 μM/mm), GS (-54 μM/mm), and FDS (-33 μM/mm). The projected total-[Hb + Mb] at 0 mm ATT ( y-intercept) was 452, 372, 620, and 456 μM for VL, RF, GS, and FDS, respectively. No differences were found between the sexes within VL, RF, or FDS, but men had a greater projected total-[Hb + Mb] at 0 mm for GS (688 ± 44 vs. 552 ± 40 μM; P < 0.05). Exclusion of the shortest source-detector distance increased total-[Hb + Mb] by 12 ± 1 μM ( P < 0.05). The present findings demonstrate that total-[Hb + Mb] should be corrected for ATT using muscle site-specific factors which are not sex specific, except in the case of GS. NEW & NOTEWORTHY Near-infrared spectroscopy (NIRS) is an important tool for physiologists and clinicians. However, adipose tissue greatly attenuates the signals from these devices. Correcting for this attenuation has been suggested based on the strength of the relationship between NIRS-derived measurements and the adipose tissue thickness. We show that this relationship is unique to the muscle site of interest but may not be sex specific. Accurate quantification of underlying tissue mandates researchers correct for adipose tissue thickness.