We hypothesized that during exercise at maximal O2 consumption (VO2max), high demand for respiratory muscle blood flow (Q) would elicit locomotor muscle vasoconstriction and compromise limb Q. Seven male cyclists (VO2max 64 +/- 6 ml.kg-1.min-1) each completed 14 exercise bouts of 2.5-min duration at VO2max on a cycle ergometer during two testing sessions. Inspiratory muscle work was either 1) reduced via a proportional-assist ventilator, 2) increased via graded resistive loads, or 3) was not manipulated (control). Arterial (brachial) and venous (femoral) blood samples, arterial blood pressure, leg Q (Qlegs; thermodilution), esophageal pressure, and O2 consumption (VO2) were measured. Within each subject and across all subjects, at constant maximal work rate, significant correlations existed (r = 0.74-0.90; P < 0.05) between work of breathing (Wb) and Qlegs (inverse), leg vascular resistance (LVR), and leg VO2 (VO2legs; inverse), and between LVR and norepinephrine spillover. Mean arterial pressure did not change with changes in Wb nor did tidal volume or minute ventilation. For a +/-50% change from control in Wb, Qlegs changed 2 l/min or 11% of control, LVR changed 13% of control, and O2 extraction did not change; thus VO2legs changed 0.4 l/min or 10% of control. Total VO2max was unchanged with loading but fell 9.3% with unloading; thus VO2legs as a percentage of total VO2max was 81% in control, increased to 89% with respiratory muscle unloading, and decreased to 71% with respiratory muscle loading. We conclude that Wb normally incurred during maximal exercise causes vasoconstriction in locomotor muscles and compromises locomotor muscle perfusion and VO2.

We investigated the role of somatosensory feedback from locomotor muscles on central motor drive (CMD) and the development of peripheral fatigue during high-intensity endurance exercise. In a double-blind, placebo-controlled design, eight cyclists randomly performed three 5 km time trials: control, interspinous ligament injection of saline (5K Plac , L3-L4) or intrathecal fentanyl (5K Fent , L3-L4) to impair cortical projection of opioid-mediated muscle afferents. Peripheral quadriceps fatigue was assessed via changes in force output pre-versus postexercise in response to supramaximal magnetic femoral nerve stimulation ( Q tw ). The CMD during the time trials was estimated via quadriceps electromyogram (iEMG). Fentanyl had no effect on quadriceps strength. Impairment of neural feedback from the locomotor muscles increased iEMG during the first 2.5 km of 5K Fent versus 5K Plac by 12 ± 3% (P < 0.05); during the second 2.5 km, iEMG was similar between trials. Power output was also 6 ± 2% higher during the first and 11 ± 2% lower during the second 2.5 km of 5K Fent versus 5K Plac (both P < 0.05). Capillary blood lactate was higher (16.3 ± 0.5 versus 12.6 ± 1.0%) and arterial haemoglobin O 2 saturation was lower (89 ± 1 versus 94 ± 1%) during 5K Fent versus 5K Plac . Exercise-induced Q tw was greater following 5K Fent versus 5K Plac (−46 ± 2 versus −33 ± 2%, P < 0.001). Our results emphasize the critical role of somatosensory feedback from working muscles on the centrally mediated determination of CMD. Attenuated afferent feedback from exercising locomotor muscles results in an overshoot in CMD and power output normally chosen by the athlete, thereby causing a greater rate of accumulation of muscle metabolites and excessive development of peripheral muscle fatigue.

Changing arterial oxygen content (C aO 2 ) has a highly sensitive influence on the rate of peripheral locomotor muscle fatigue development. We examined the effects of C aO 2 on exercise performance and its interaction with peripheral quadriceps fatigue. Eight trained males performed four 5 km cycling time trials (power output voluntarily adjustable) at four levels of C aO 2 (17.6-24.4 ml O 2 dl −1 ), induced by variations in inspired O 2 fraction (0.15-1.0). Peripheral quadriceps fatigue was assessed via changes in force output pre-versus post-exercise in response to supra-maximal magnetic femoral nerve stimulation (ΔQ tw ; 1-100 Hz). Central neural drive during the time trials was estimated via quadriceps electromyogram. Increased C aO 2 from hypoxia to hyperoxia resulted in parallel increases in central neural output (43%) and power output (30%) during cycling and improved time trial performance (12%); however, the magnitude of ΔQ tw (−33 to −35%) induced by the exercise was not different among the four time trials (P > 0.2). These effects of C aO 2 on time trial performance and ΔQ tw were reproducible (coefficient of variation = 1-6%) over repeated trials at each F IO 2 on separate days. In the same subjects, changing C aO 2 also affected performance time to exhaustion at a fixed work rate, but similarly there was no effect of ΔC aO 2 on peripheral fatigue. Based on these results, we hypothesize that the effect of C aO 2 on locomotor muscle power output and exercise performance time is determined to a significant extent by the regulation of central motor output to the working muscle in order that peripheral muscle fatigue does not exceed a critical threshold.

We investigated the role of somatosensory feedback on cardioventilatory responses to rhythmic exercise in five men. In a double-blind, placebo-controlled design, subjects performed the same leg cycling exercise (50/100/150/325 ± 19 W, 3 min each) under placebo conditions (interspinous saline, L(3)-L(4)) and with lumbar intrathecal fentanyl impairing central projection of spinal opioid receptor-sensitive muscle afferents. Quadriceps strength was similar before and after fentanyl administration. To evaluate whether a cephalad migration of fentanyl affected cardioventilatory control centers in the brain stem, we compared resting ventilatory responses to hypercapnia (HCVR) and cardioventilatory responses to arm vs. leg cycling exercise after each injection. Similar HCVR and minor effects of fentanyl on cardioventilatory responses to arm exercise excluded direct medullary effects of fentanyl. Central command during leg exercise was estimated via quadriceps electromyogram. No differences between conditions were found in resting heart rate (HR), ventilation [minute ventilation (VE)], or mean arterial pressure (MAP). Quadriceps electromyogram, O(2) consumption (VO(2)), and plasma lactate were similar in both conditions at the four steady-state workloads. Compared with placebo, a substantial hypoventilation during fentanyl exercise was indicated by the 8-17% reduction in VE/CO(2) production (VCO(2)) secondary to a reduced breathing frequency, leading to average increases of 4-7 Torr in end-tidal PCO(2) (P < 0.001) and a reduced hemoglobin saturation (-3 ± 1%; P < 0.05) at the heaviest workload (∼90% maximal VO(2)) with fentanyl. HR was reduced 2-8%, MAP 8-13%, and ratings of perceived exertion by 13% during fentanyl vs. placebo exercise (P < 0.05). These findings demonstrate the essential contribution of muscle afferent feedback to the ventilatory, cardiovascular, and perceptual responses to rhythmic exercise in humans, even in the presence of unaltered contributions from other major inputs to cardioventilatory control.

We examined the effects of hypoxia severity on peripheral versus central determinants of exercise performance. Eight cyclists performed constant-load exercise to exhaustion at various fractions of inspired O 2 fraction (F IO 2 0.21/0.15/0.10). At task failure (pedal frequency < 70% target) arterial hypoxaemia was surreptitiously reversed via acute O 2 supplementation (F IO 2 = 0.30) and subjects were encouraged to continue exercising. Peripheral fatigue was assessed via changes in potentiated quadriceps twitch force (ΔQ tw,pot ) as measured pre-versus post-exercise in response to supramaximal femoral nerve stimulation. At task failure in normoxia (haemoglobin saturation (S pO 2 ) ∼94%, 656 ± 82 s) and moderate hypoxia (S pO 2 ∼82%, 278 ± 16 s), hyperoxygenation had no significant effect on prolonging endurance time. However, following task failure in severe hypoxia (S pO 2 ∼67%; 125 ± 6 s), hyperoxygenation elicited a significant prolongation of time to exhaustion (171 ± 61%). The magnitude of ΔQ tw,pot at exhaustion was not different among the three trials (−35% to −36%, P = 0.8). Furthermore, quadriceps integrated EMG, blood lactate, heart rate, and effort perceptions all rose significantly throughout exercise, and to a similar extent at exhaustion following hyperoxygenation at all levels of arterial oxygenation. Since hyperoxygenation prolonged exercise time only in severe hypoxia, we repeated this trial and assessed peripheral fatigue following task failure prior to hyperoxygenation (125 ± 6 s). Although Q tw,pot was reduced from pre-exercise baseline (−23%; P < 0.01), peripheral fatigue was substantially less (P < 0.01) than that observed at task failure in normoxia and moderate hypoxia. We conclude that across the range of normoxia to severe hypoxia, the major determinants of central motor output and exercise performance switches from a predominantly peripheral origin of fatigue to a hypoxia-sensitive central component of fatigue, probably involving brain hypoxic effects on effort perception.