The exercise pressor reflex - a pressure-raising mechanism with a limited role in regulating leg perfusion during locomotion in young healthy men.

We investigated the role of the exercise pressor reflex (EPR) in regulating the haemodynamic response to locomotor exercise. Eight healthy participants (23 ± 3 years, V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ : 49 ± 6 ml/kg/min) performed constant-load cycling exercise (∼36/43/52/98% V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ ; 4 min each) without (CTRL) and with (FENT) lumbar intrathecal fentanyl attenuating group III/IV locomotor muscle afferent feedback and, thus, the EPR. To avoid different respiratory muscle metaboreflex and arterial chemoreflex activation during FENT, subjects mimicked the ventilatory response recorded during CTRL. Arterial and leg perfusion pressure (femoral arterial and venous catheters), femoral blood flow (Doppler-ultrasound), microvascular quadriceps blood flow index (indocyanine green), cardiac output (inert gas breathing), and systemic and leg vascular conductance were quantified during exercise. There were no cardiovascular and ventilatory differences between conditions at rest. Pulmonary ventilation, arterial blood gases and oxyhaemoglobin saturation were not different during exercise. Furthermore, cardiac output (-2% to -12%), arterial pressure (-7% to -15%) and leg perfusion pressure (-8% to -22%) were lower, and systemic (up to 16%) and leg (up to 27%) vascular conductance were higher during FENT compared to CTRL. Leg blood flow, microvascular quadriceps blood flow index, and leg O2 -transport and utilization were not different between conditions (P > 0.5). These findings reflect a critical role of the EPR in the autonomic control of the heart, vasculature and, ultimately, arterial pressure during locomotor exercise. However, the lack of a net effect of the EPR on leg blood flow challenges the idea of this cardiovascular reflex as a key determinant of leg O2 -transport during locomotor exercise in healthy, young individuals. KEY POINTS: The role of the exercise pressor reflex (EPR) in regulating leg O2 -transport during human locomotion remains uncertain. We investigated the influence of the EPR on the cardiovascular response to cycling exercise. Lumbar intrathecal fentanyl was used to block group III/IV leg muscle afferents and debilitate the EPR at intensities ranging from 30% to 100% V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{max}}}}$ . To avoid different respiratory muscle metaboreflex and arterial chemoreflex activation during exercise with blocked leg muscle afferents, subjects mimicked the ventilatory response recorded during control exercise. Afferent blockade increased leg and systemic vascular conductance, but reduced cardiac output and arterial-pressure, with no net effect on leg blood flow. The EPR influenced the cardiovascular response to cycling exercise by contributing to the autonomic control of the heart and vasculature, but did not affect leg blood flow. These findings challenge the idea of the EPR as a key determinant of leg O2 -transport during locomotor exercise in healthy, young individuals.

Effects of exercise induced muscle damage on cardiovascular responses to isometric muscle contractions and post-exercise circulatory occlusion.

PURPOSE: The aim of the present study was to investigate whether exercise-induced muscle damage (EIMD) influences cardiovascular responses to isometric exercise and post-exercise circulatory occlusion (PECO). We hypothesized that EIMD would increase muscle afferent sensitivity and, accordingly, increase blood pressure responses to exercise and PECO. METHODS: Eleven male and nine female participants performed unilateral isometric knee extension at 30% of maximal voluntary contraction (MVC) for 3-min. A thigh cuff was rapidly inflated to 250 mmHg for two min PECO, followed by 3 min recovery. Heart rate and blood pressure were monitored beat-by-beat, with stroke volume and cardiac output estimated from the Modelflow algorithm. Measurements were taken before and 48 h after completing eccentric knee-extension contractions to induce muscle damage (EIMD). RESULTS: EIMD caused 21% decrease in MVC (baseline: 634.6 ± 229.3 N, 48 h: 504.0 ± 160 N), and a 17-fold increase in perceived soreness using a visual-analogue scale (0-100 mm; VASSQ) (both p < 0.001). CV responses to exercise and PECO were not different between pre and post EIMD. However, mean arterial pressure (MAP) was higher during the recovery phase after EIMD (p < 0.05). Significant associations were found between increases in MAP during exercise and VASSQ, Rate of Perceived Exertion (RPE) and Pain after EIMD only (all p < 0.05). CONCLUSION: The MAP correlations with muscle soreness, RPE and Pain during contractions of damaged muscles suggests that higher afferent activity was associated with higher MAP responses to exercise.

Aging reduces the maximal level of peripheral fatigue tolerable and impairs exercise capacity.

The aim of the present study was to determine the magnitude of the maximal level of peripheral fatigue attainable (fatigue threshold) during an all-out intermittent isometric knee-extensor protocol in both younger (24 ± 1 yr, n = 12) and older (60 ± 2 yr, n = 12) participants to provide new insights into the effects of aging on neuromuscular function. Participants performed two experimental sessions, in which they performed 60 maximal voluntary contractions (MVCs; 3 s of contraction, 2 s of relaxation). One trial was performed in the unfatigued state (CTRL) and one other following fatiguing neuromuscular electrical stimulation of the quadriceps (FNMES). Peripheral fatigue was quantified via pre/postexercise decrease in quadriceps twitch force (∆Ptw). Critical force (CF) was determined as the mean force output of the last 12 contractions, whereas W' was calculated as the area above CF. Although FNMES led to a significant decrease in Ptw before performing the 60-MVCs protocol (P = 0.024), ∆Ptw was not different between CTRL and FNMES for both the young group (P = 0.491) and the old group (P = 0.523). However, this peripheral fatigue threshold was significantly greater in young versus old participants (∆Ptw = -48 ± 10% vs. -29 ± 13%, respectively, P = 0.028). In CTRL, W' was 55 ± 13% lower in the old group than in the young group (P < 0.001), but CF was similar (326 ± 10 N vs. 322 ± 12 N, respectively, P = 0.941). ∆Ptw was correlated with W', independently of age (r2 = 0.84, P < 0.001). Exercise performance decreases with aging consequent to a lower tolerance to peripheral fatigue. However, the peripheral fatigue threshold mechanism persists with healthy aging and continues to play a protective role in preserving locomotor muscle function during exercise.

Metabo- and mechanoreceptor expression in human heart failure: Relationships with the locomotor muscle afferent influence on exercise responses.

NEW FINDINGS: What is the central question of this study? How do locomotor muscle metabo- and mechanoreceptor expression compare in heart failure patients and controls? Do relationships exist between the protein expression and cardiopulmonary responses during exercise with locomotor muscle neural afferent feedback inhibition? What is the main finding and its importance? Heart failure patients exhibited greater protein expression of transient receptor potential vanilloid type 1 and cyclooxygenase-2 than controls. These findings are important as they identify receptors that may underlie the augmented locomotor muscle neural afferent feedback in heart failure. ABSTRACT: Heart failure patients with reduced ejection fraction (HFrEF) exhibit abnormal locomotor group III/IV afferent feedback during exercise; however, the underlying mechanisms are unclear. Therefore, the purpose of this study was to determine (1) metabo- and mechanoreceptor expression in HFrEF and controls and (2) relationships between receptor expression and changes in cardiopulmonary responses with afferent inhibition. Ten controls and six HFrEF performed 5 min of cycling exercise at 65% peak workload with lumbar intrathecal fentanyl (FENT) or placebo (PLA). Arterial blood pressure and catecholamines were measured via radial artery catheter. A vastus lateralis muscle biopsy was performed to quantify cyclooxygenase-2 (COX-2), purinergic 2X3 (P2X3 ), transient receptor potential vanilloid type 1 (TRPV 1), acid-sensing ion channel 3 (ASIC3 ), Piezo 1 and Piezo 2 protein expression. TRPV 1 and COX-2 protein expression was greater in HFrEF than controls (both P < 0.04), while P2X3 , ASIC3 , and Piezo 1 and 2 were not different between groups (all P > 0.16). In all participants, COX-2 protein expression was related to the percentage change in ventilation (r = -0.66) and mean arterial pressure (MAP) (r = -0.82) (both P < 0.01) with FENT (relative to PLA) during exercise. In controls, TRPV 1 protein expression was related to the percentage change in systolic blood pressure (r = -0.77, P = 0.02) and MAP (r = -0.72, P = 0.03) with FENT (relative to PLA) during exercise. TRPV 1 and COX-2 protein levels are elevated in HFrEF compared to controls. These findings suggest that the elevated TRPV 1 and COX-2 expression may contribute to the exaggerated locomotor muscle afferent feedback during cycling exercise in HFrEF.

Centrally-mediated regulation of peripheral fatigue during knee extensor exercise and consequences on the force-duration relationship in older men.

The aim of the present study was to investigate the existence of a critical threshold beyond which peripheral fatigue would not further decrease during knee extensor (KE) exercise in older men, and the consequences of this mechanism on the force-duration relationship. Twelve old men (59 ± 2 years) randomly performed two different sessions, in which they performed 60 maximum voluntary contractions (MVC; 3s contraction, 2s relaxation). One trial was performed in the unfatigued state (CTRL) and one other following fatiguing neuromuscular electrical stimulation of the KE (FNMES). Peripheral and central fatigue were quantified via pre/post-exercise decreases in quadriceps twitch-force (Δ Ptw) and voluntary activation (ΔVA). Critical torque (CT) was determined as the mean force of the last 12 contractions while W' was calculated as the area above CT. Compared with CTRL, pre-fatigue (Δ Ptw = -10.3 ± 6.2%) resulted in a significant (p < 0.05) reduction in W' (-18.2 ± 1.6%) in FNMES. However, CT (∼964 N), ΔVA (∼15%) and Δ Ptw (∼25%) post-MVCs were similar between both conditions. In CTRL, W' was correlated with Δ Ptw (r 2 = 0.78). Moreover, the difference in W' between CTRL and FNMES was correlated with the level of pre-fatigue induced in FNMES (r 2 = 0.76). These findings document that peripheral fatigue is confined to an individual threshold during KE exercise in older men. Furthermore, correlative results suggest that mechanisms regulating peripheral fatigue to a critical threshold also restrict W', and therefore play a role in exercise capacity in older men.

Critical Peripheral Fatigue Thresholds Among Different Force-Velocity Conditions: An Individual-Based Model Approach.

During high intensity exercise, metabosensitive muscle afferents are thought to inhibit the motor drive command to restrict the level of peripheral fatigue to an individual's critical threshold. No evidence exists of an individual relationship between peripheral fatigue and the decrease in voluntary activation reached after prolonged all-out exercise. Moreover, there is no explanation for the previously reported large decrease in voluntary activation despite low metabolic stress during high force contractions. Thirteen active men completed two maximal intensity isokinetic knee extension tests (160 contractions) under conditions of low force - high velocity and high force - low velocity. Neuromuscular testing including maximal torque, evoked torque and voluntary activation, was done every 20 contractions. The exponential modeling of these variables over time allowed us to predict the stable state (asymptote) and the rate of decrease (curvature constant). For both high and low force contractions the evoked torque and voluntary activation asymptotes were negatively correlated (R 2 = 0.49 and R 2 = 0.46, respectively). The evoked torque asymptotes of the high and low force conditions were positively correlated (R 2 = 0.49). For the high force contractions, the evoked torque and voluntary activation curvature constant were negatively correlated (R 2 = 0.43). These results support the idea that a restrained central motor drive keeps peripheral fatigue under this threshold. Furthermore, an individual would show similar fatigue sensibility regardless of the force generated. These data also suggest that the decrease in voluntary activation might not have been triggered by peripheral perturbations during the first high force contractions.