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Analyzing <em>Ex Vivo</em> Metabolic Flux in Splenic and Cardiac Macrophages and Bone Marrow Monocytes

Metabolic reprogramming is a hallmark of monocyte/macrophage activation and polarization between pro- and anti-inflammatory states. For example, ...

University of Mississippi Medical Center

The application of blood flow restriction (BFR) to low-intensity exercise may be able to increase strength not only in the trained limb but also in the homologous untrained limb. Whether this effect is repeatable and how that change compares to that observed with higher intensity exercise is unknown.

Blood flow restriction augments the cross-education effect of isometric handgrip training.

Blood flow restriction pressures are set relative to the lowest pressure needed to occlude blood flow with that specific cuff. Due to pressure limitations of some devices, it is often not possible to occlude blood flow in all subjects and apply a known relative pressure in the lower body with a 5 cm wide cuff.. To use a device capable of generating high pressures (up to 907 mmHg) to create and validate an estimation equation for the 5 cm cuff in the lower body using a 12 cm cuff.. 170 participants had their arterial occlusion pressure (AOP) with a 5 cm and 12 cm cuff and their thigh circumference measured in their right leg. The sample was randomly allocated to a prediction group (66%) and validation group (33%). Thigh circumference and 12 cm AOP were used as predictors. A Bland-Altman plot was constructed to assess agreement between measured and predicted values.. The mean difference (95% confidence interval) between the observed (336.8 mmHg) and the predicted (343.9 mmHg) 5 cm AOP was 7.1 (-11.9, 26.1) mmHg. The 95% limits of agreement were -133.6 to 147.8 mmHg. There was a negative relationship between the difference and the average of predicted and measured 5 cm AOP (= -0.317,= 0.000043).. Although this was the first study to quantify AOP over 600 mmHg with a 5 cm cuff, our equation is not valid across all levels of pressure. If possible, larger cuff widths should be employed in the lower body.

Blood flow restriction pressure for narrow cuffs (5 cm) cannot be estimated with precision.

We sought to determine the effects of blood flow restriction (BFR) on exercise-induced hypoalgesia, specifically using low-load (LL) resistance exercise (30% 1RM) protocols that accounted for each individual's local muscular endurance capabilities. Forty-four participants completed four conditions: (1) 70% of maximal BFR repetitions with blood flow restriction (LL+BFR exercise); (2) 70% maximal BFR repetitions without LL+BFR (LL exercise); (3) 70% maximal free flow repetitions (LL+EFFORT exercise); (4) time-matched, non-exercise control (CON). Pressure pain threshold (PPT) was measured before and after exercise. Ischaemic pain threshold and tolerance was assessed only at post. The change in upper body PPT was greater for LL+BFR exercise compared to LL exercise [difference of 0.15 (0.35) kg/cm], LL+EFFORT exercise [difference of 0.23 (0.45) kg/cm], and the CON condition. The change in lower body PPT was greater for LL+BFR exercise compared to LL exercise [difference of 0.40 (0.55) kg/cm], LL+EFFORT exercise [difference of 0.36 (0.62) kg/cm], and the CON condition. Ischaemic pain thresholds and tolerances did not change. Submaximal exercise with BFR resulted in systemic increases in PPT but had no influence on ischaemic pain sensitivity. This effect is likely unique to BFR as we did not see changes in the effort matched free flow condition.

Blood flow restriction augments exercise-induced pressure pain thresholds over repetition and effort matched conditions.

The literature predominantly addresses cross-education of strength in the dominant limb rather than the non-dominant limb, guided by the hypothesis of an asymmetrical transfer of strength from unilateral training protocols. The purpose of the study was to review the literature and determine how much evidence was available to support this claim. A meta-analysis was performed to estimate the magnitude of this hypothesized asymmetrical transfer of strength.

Is there evidence for the asymmetrical transfer of strength to an untrained limb?

It was previously hypothesized that the cross-education of strength is asymmetrical, where a greater transfer of strength is observed from the dominant to the non-dominant limb. The purpose of this study was to examine if the magnitude of cross-education of strength differed between dominant and non-dominant limbs following unilateral high-load resistance training. One hundred and twenty-two participants were randomized to one of the three groups: 1) training on the dominant arm (D-Only), 2) training on the non-dominant arm (ND-Only) and 3) a time-matched non-exercise control (Control). The training groups completed 6 weeks (18 sessions) of unilateral elbow flexion exercise. Each training session started with one-repetition maximum (1RM) training (≤ five attempts), followed by four sets of high-load exercise (i.e. 8-12RM). Strength changes of the untrained arm were compared between groups. Changes in the strength of the untrained arm were greater in D-Only (1.5 kg) and ND-Only (1.3 kg) compared to Control (-0.2 kg), without differences between D-Only and ND-Only. Unilateral resistance training increased strength in the opposite untrained arm, and the magnitude of this effect was similar regardless of which arm was trained. However, there is still considerable uncertainty on this topic and additional research is warranted to confirm the current findings.

Unilateral high-load resistance training induced a similar cross-education of strength between the dominant and non-dominant arm.

Progressive overload describes the gradual increase of stress placed on the body during exercise training, and is often quantified (i.e. in resistance training studies) through increases in total training volume (i.e. sets × repetitions × load) from the first to final week of the exercise training intervention. Within the literature, it has become increasingly common for authors to discuss skeletal muscle growth adaptations in the context of increases in total training volume (i.e. the magnitude progression in total training volume). The present manuscript discusses a physiological rationale for progressive overload and then explains why, in our opinion, quantifying the progression of total training volume within research investigations tells very little about muscle growth adaptations to resistance training. Our opinion is based on the following research findings: (1) a noncausal connection between increases in total training volume (i.e. progressively overloading the resistance exercise stimulus) and increases in skeletal muscle size; (2) similar changes in total training volume may not always produce similar increases in muscle size; and (3) the ability to exercise more and consequently amass larger increases in total training volume may not inherently produce more skeletal muscle growth. The methodology of quantifying changes in total training volume may therefore provide a means through which researchers can mathematically determine the total amount of external 'work' performed within a resistance training study. It may not, however, always explain muscle growth adaptations.

Progression of total training volume in resistance training studies and its application to skeletal muscle growth.

To investigate the effects of high-intensity contractions and low-intensity contractions with and without blood flow restriction on changes in blood pressure and hemodynamic parameters. A total of 179 participants (18-35 years) were randomly assigned to one of three training groups that exercised 3 times per week for six weeks or a non-exercise control group. The groups are as follows: 1) Control [CON,  = 44]; 2) completed 4 sets of two-minute isometric contractions at 30% maximal voluntary contraction [LI,  = 47]; 3) completed 4 sets of two-minute isometric contractions at 30% maximal voluntary contraction with a 12 cm cuff inflated to 50% of arterial occlusion pressure [LI+BFR,  = 41]; or 4) completed 4 maximal isometric contractions lasting 5 seconds [MAX,  = 47]. Blood pressure, vascular resistance, and reactive hyperemia were measured at pre and post. Data are presented as means (SD). There was no evidence that SBP (BF: 0.066), DBP (BF: 0.057), vascular resistance (BF: 0.085), or peak reactive hyperemia changed (BF: 0.044) or A.U.C. (BF: 0.074). Change scores for SBP were 1.1 (6.7), 0.7 (5.8), -0.4 (6.5), and -0.9 (6.3) mmHg for CON, LI, LI+BFR, and MAX, respectively. DBP change scores were 1.5 (6.6), 1.5 (7), -0.7 (5.9), and 0.3 (6.3) mmHg for CON, LI, LI+BFR, and MAX, respectively. Although recommended as a non-pharmacological method of blood pressure control, isometric exercise with or without BFR did not lower blood pressure. Future work could examine the inclusion of a daily strength test prior to the low intensity protocol.

The Effect of Isometric Handgrip Training With and Without Blood Flow Restriction on Changes in Resting Blood Pressure.

Training one limb with a high-load has been shown to augment strength changes in the opposite limb training with a low-load (via cross-education of strength), indicating that within-subject models can be problematic when investigating strength changes. This study examined if the cross-education of strength from unilateral high-load training could augment the strength changes in the opposite arm undergoing the same unilateral high-load training. 160 participants were randomized to one of four groups: (1) training on the dominant arm followed by the non-dominant arm (D + ND), (2) training on the dominant arm only (D-Only), (3) training on the non-dominant arm only (ND-Only), and (4) a non-exercise control. All exercise groups performed 18 sessions of unilateral high-load elbow flexion exercise over 6 weeks. Participants were compared for changes in 1RM strength and muscle thickness. Changes in strength of the non-dominant arm were greater in D + ND (2.7 kg) and ND-Only (2.6 kg) compared to D-Only (1.5 kg) and control (-0.2 kg), while the changes were greater in D-Only compared to control. The same finding was observed in the dominant arm. Only the arms being directly trained observed increases in muscle thickness. Unilateral high-load resistance training increased strength in the opposite untrained arm, without changes in muscle thickness. This cross-education of strength did not augment the strength changes in the contralateral arm undergoing the same unilateral high-load training. However, it does not necessarily indicate that within-subject models are methodologically sound to investigate strength change if both limbs are trained with a high-load.

Does Unilateral High-Load Resistance Training Influence Strength Change in the Contralateral Arm Also Undergoing High-Load Training?

To determine 1) whether the relationship between isometric training and muscle growth depends on baseline blood flow or is mediated by a change in blood flow, and 2) whether muscle growth mediates changes in maximal isometric strength.

Investigating the Influence of Limb Blood Flow on Contraction-Induced Muscle Growth and the Impact of That Growth on Changes in Maximal Strength.

Blood flow restricted exercise appears to be more discomforting than the same exercise without blood flow restriction. Changes in discomfort have not been investigated following repeated bouts of isometric exercise. It is possible that the isometric contractions may further trap metabolites resulting in greater discomfort. The purpose was to investigate the effects of six weeks of isometric handgrip exercise on perceived discomfort and willingness to continue with that form of exercise. 135 participants trained three times a week for six-weeks. The training consisted of four sets of 2-min low-intensity contractions (at 30% of their maximal voluntary contraction) with blood flow restriction (LI + BFR) and without blood flow restriction (LI). The maximal contraction group performed four, five second maximal contractions (MAX). Discomfort was measured post-exercise on the first, ninth, and last training session using the CR10+ scale. Changes in discomfort from the 1 to the 18 session were greater in the LI [-1.7 (1.7) AU] (BF = 6952.769) and LI + BFR [-1.5 (1.9) AU] (BF = 404.996) when compared to MAX group [0.04 (1.5) AU]. There was no difference between LI and LI + BFR (BF = 0.241). Although there were differences in discomfort, there was no difference in the desire to continue the same exercise amongst groups (BF = 0.208). Discomfort decreased more in both low intensity groups compared to the MAX group. Despite greater decreases in discomfort there was no difference in willingness to continue with the same form of exercise. This suggests other factors besides discomfort may influence an individual's willingness to continue with the same type of exercise.

Article	Year
Blood flow restriction augments the cross-education effect of isometric handgrip training. European journal of applied physiology\| PubMed ID: 38168713	2024
Blood flow restriction pressure for narrow cuffs (5 cm) cannot be estimated with precision. Physiological measurement\| PubMed ID: 38330491	2024
Blood flow restriction augments exercise-induced pressure pain thresholds over repetition and effort matched conditions. Journal of sports sciences\| PubMed ID: 38412241	2024
Is there evidence for the asymmetrical transfer of strength to an untrained limb? European journal of applied physiology\| PubMed ID: 38568258	2024
Unilateral high-load resistance training induced a similar cross-education of strength between the dominant and non-dominant arm. Journal of sports sciences\| PubMed ID: 39115420	2024
Progression of total training volume in resistance training studies and its application to skeletal muscle growth. Physiological measurement\| PubMed ID: 39178897	2024
The Effect of Isometric Handgrip Training With and Without Blood Flow Restriction on Changes in Resting Blood Pressure. Research quarterly for exercise and sport\| PubMed ID: 39565879	2024
Does Unilateral High-Load Resistance Training Influence Strength Change in the Contralateral Arm Also Undergoing High-Load Training? Scandinavian journal of medicine & science in sports\| PubMed ID: 39582380	2024
Investigating the Influence of Limb Blood Flow on Contraction-Induced Muscle Growth and the Impact of That Growth on Changes in Maximal Strength. Medicine and science in sports and exercise\| PubMed ID: 39604154	2025
Perceived Discomfort is Decreased After Repeated Bouts of Isometric Handgrip Exercise With and Without Blood Flow Restriction. Perceptual and motor skills\| PubMed ID: 40013726	2025

Robert W. Spitz

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