Lee M. Romer

Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans

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 O2 fraction (FIO2 0.21/0.15/0.10). At task failure (pedal frequency < 70% target) arterial hypoxaemia was surreptitiously reversed via acute O2 supplementation (FIO2= 0.30) and subjects were encouraged to continue exercising. Peripheral fatigue was assessed via changes in potentiated quadriceps twitch force (ΔQtw,pot) as measured pre‐ versus post‐exercise in response to supramaximal femoral nerve stimulation. At task failure in normoxia (haemoglobin saturation (SpO2) ∼94%, 656 ± 82 s) and moderate hypoxia (SpO2∼82%, 278 ± 16 s), hyperoxygenation had no significant effect on prolonging endurance time. However, following task failure in severe hypoxia (SpO2∼67%; 125 ± 6 s), hyperoxygenation elicited a significant prolongation of time to exhaustion (171 ± 61%). The magnitude of ΔQtw,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 Qtw,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.

Consequences of exercise-induced respiratory muscle work

We briefly review the evidence for a hypothesis, which links the ventilatory response to heavy intensity, sustained exercise-to-exercise performance limitation in health. A key step in this linkage is a respiratory muscle fatigue-induced metaboreflex, which increases sympathetic vasoconstrictor outflow, causing reduced blood flow to locomotor muscles and locomotor muscle fatigue. In turn, the limb fatigue comprises an important dual contribution to both peripheral and central fatigue mechanisms, which contribute to limiting exercise performance. Clinical implications for respiratory limitations to exercise in patients with chronic obstructive lung disease (COPD) and chronic heart failure (CHF) are discussed and key unresolved problems are outlined.

Effects of inspiratory muscle training on time-trial performance in trained cyclists

We evaluated the effects of specific inspiratory muscle training on simulated time-trial performance in trained cyclists. Using a double-blind, placebo-controlled design, 16 male cyclists (VO 2max = 64 - 2 ml·kg -1 ·min -1 ; mean - sx ¥ ) were assigned at random to either an experimental (pressure-threshold inspiratory muscle training) or sham-training control (placebo) group. Pulmonary function, maximum dynamic inspiratory muscle function and the physiological and perceptual responses to maximal incremental cycling were assessed. Simulated time-trial performance (20 and 40 km) was quantified as the time to complete pre-set amounts of work. Pulmonary function was unchanged after the intervention, but dynamic inspiratory muscle function improved in the inspiratory muscle training group ( P h 0.05). After the intervention, the inspiratory muscle training group experienced a reduction in the perception of respiratory and peripheral effort (Borg CR10: 16 - 4% and 18 - 4% respectively; compared with placebo, P h 0.01) and completed the simulated 20 and 40 km time-trials faster than the placebo group [66 - 30 and 115 - 38 s (3.8 - 1.7% and 4.6 - 1.9%) faster respectively; P = 0.025 and 0.009]. These results support evidence that specific inspiratory muscle training attenuates the perceptual response to maximal incremental exercise. Furthermore, they provide evidence of performance enhancements in competitive cyclists after inspiratory muscle training.

Effect of inspiratory muscle work on peripheral fatigue of locomotor muscles in healthy humans

The work of breathing required during maximal exercise compromises blood flow to limb locomotor muscles and reduces exercise performance. We asked if force output of the inspiratory muscles affected exercise‐induced peripheral fatigue of locomotor muscles. Eight male cyclists exercised at ≥ 90% peak O2 uptake to exhaustion (CTRL). On a separate occasion, subjects exercised for the same duration and power output as CTRL (13.2 ± 0.9 min, 292 W), but force output of the inspiratory muscles was reduced (−56%versus CTRL) using a proportional assist ventilator (PAV). Subjects also exercised to exhaustion (7.9 ± 0.6 min, 292 W) while force output of the inspiratory muscles was increased (+80%versus CTRL) via inspiratory resistive loads (IRLs), and again for the same duration and power output with breathing unimpeded (IRL‐CTRL). Quadriceps twitch force (Qtw), in response to supramaximal paired magnetic stimuli of the femoral nerve (1–100 Hz), was assessed pre‐ and at 2.5 through to 70 min postexercise. Immediately after CTRL exercise, Qtw was reduced −28 ± 5% below pre‐exercise baseline and this reduction was attenuated following PAV exercise (−20 ± 5%; P < 0.05). Conversely, increasing the force output of the inspiratory muscles (IRL) exacerbated exercise‐induced quadriceps muscle fatigue (Qtw=−12 ± 8% IRL‐CTRL versus−20 ± 7% IRL; P < 0.05). Repeat studies between days showed that the effects of exercise per se, and of superimposed inspiratory muscle loading on quadriceps fatigue were highly reproducible. In conclusion, peripheral fatigue of locomotor muscles resulting from high‐intensity sustained exercise is, in part, due to the accompanying high levels of respiratory muscle work.

Inspiratory muscle fatigue in trained cyclists: effects of inspiratory muscle training

PURPOSE This study evaluated the influence of simulated 20- and 40-km time trials upon postexercise inspiratory muscle function of trained competitive cyclists. In addition, we examined the influence of specific inspiratory muscle training (IMT) upon the responses observed. METHODS Using a double-blind placebo-controlled design, 16 male cyclists (mean +/- SEM VO2max 64 +/- 2 mL.kg-1.min-1) were assigned randomly to either an experimental (IMT) or sham-training control (placebo) group. Maximum static and dynamic inspiratory muscle function was assessed immediately pre- and <2, 10, and 30 min post-simulated 20- and 40-km time trials before and after 6-wk of IMT or sham-IMT. RESULTS Maximum inspiratory mouth pressure (P0) measured within 2 min of completing the 20- and 40-km time trial rides was reduced by 18% and 13%, respectively, and remained below preexercise values at 30 min. The 20- and 40-km time trials induced a reduction in inspiratory flow rate at 30% P0 by 14% and 6% in the IMT group versus 13% and 7% for the placebo group, and also remained below preexercise values at 30 min. There was also a significant slowing of inspiratory muscle relaxation rate postexercise; these trends were almost completely reversed by 30 min postexercise. Significant improvements in 20- and 40-km time trial performance were seen (3.8 +/- 1.7% and 4.6 +/- 1.9%, respectively; P < 0.05) and postexercise reductions in muscle function were attenuated with IMT. CONCLUSION These data support existing evidence that there is significant global inspiratory muscle fatigue after sustained heavy endurance exercise. Furthermore, the present study provides new evidence that performance enhancements observed after IMT are accompanied by a decrease in inspiratory muscle fatigue.

Intrapulmonary shunting and pulmonary gas exchange during normoxic and hypoxic exercise in healthy humans

Exercise-induced intrapulmonary arteriovenous shunting, as detected by saline contrast echocardiography, has been demonstrated in healthy humans. We have previously suggested that increases in both pulmonary pressures and blood flow associated with exercise are responsible for opening these intrapulmonary arteriovenous pathways. In the present study, we hypothesized that, although cardiac output and pulmonary pressures would be higher in hypoxia, the potent pulmonary vasoconstrictor effect of hypoxia would actually attenuate exercise-induced intrapulmonary shunting. Using saline contrast echocardiography, we examined nine healthy men during incremental (65 W + 30 W/2 min) cycle exercise to exhaustion in normoxia and hypoxia (fraction of inspired O(2) = 0.12). Contrast injections were made into a peripheral vein at rest and during exercise and recovery (3-5 min postexercise) with pulmonary gas exchange measured simultaneously. At rest, no subject demonstrated intrapulmonary shunting in normoxia [arterial Po(2) (Pa(O(2))) = 98 +/- 10 Torr], whereas in hypoxia (Pa(O(2)) = 47 +/- 5 Torr), intrapulmonary shunting developed in 3/9 subjects. During exercise, approximately 90% (8/9) of the subjects shunted during normoxia, whereas all subjects shunted during hypoxia. Four of the nine subjects shunted at a lower workload in hypoxia. Furthermore, all subjects continued to shunt at 3 min, and five subjects shunted at 5 min postexercise in hypoxia. Hypoxia has acute effects by inducing intrapulmonary arteriovenous shunt pathways at rest and during exercise and has long-term effects by maintaining patency of these vessels during recovery. Whether oxygen tension specifically regulates these novel pathways or opens them indirectly via effects on the conventional pulmonary vasculature remains unclear.

Supraspinal fatigue after normoxic and hypoxic exercise in humans

•  Processes leading to fatigue occur within the exercising muscle (peripheral fatigue) and the nervous system (central fatigue). •  We asked whether central processes of fatigue would be increased after strenuous exercise in environments where oxygen availability is reduced (hypoxia) compared to the same absolute exercise intensity at sea‐level. •  Our main finding was that the contribution of central processes to fatigue was increased after exercise in hypoxia (equivalent to ∼3800 m above sea‐level). •  The greater amount of central fatigue in hypoxia was due to suboptimal neural output from the brain and was associated with reductions in oxygen availability. •  The findings provide a plausible mechanism for why exercise performance is impaired at high altitude, and might help our understanding of exercise limitation in patients with reduced oxygen delivery to the brain.

Specificity and Reversibility of Inspiratory Muscle Training

PURPOSE The purpose of this study was to evaluate the pressure-flow specificity of adaptations to inspiratory muscle training (IMT), in addition to the temporal effects of detraining and reduced frequency of training upon these adaptations. METHODS Twenty-four healthy subjects were assigned randomly to one of four groups (A: low-flow-high-pressure IMT; B: high-flow-low-pressure IMT; C: intermediate flow-pressure IMT; and D: no IMT). Subjects performed IMT 6 d.wk(-1) for 9 wk, and inspiratory muscle function was evaluated at baseline and every 3 wk. Groups A, B, and C were then assigned randomly to either a maintenance group (M) (IMT 2 d.wk(-1) ) or a detraining group (DT) (no IMT). Inspiratory muscle function was reassessed at 9 and 18 wk post-IMT. RESULTS At 9 wk, group A exhibited the largest increase in pressure, B a large increase in flow, C more uniform increases in pressure and flow, and D no changes in pressure or flow. Maximum inspiratory muscle power increased in groups A, B, and C by 48 +/- 3%, 25 +/- 3%, and 64 +/- 3%, respectively (mean +/- SEM, P < or = 0.01). Maximum rate of pressure development increased in groups A, B, and C by 59 +/- 1%, 10 +/- 1%, and 29 +/- 1%, respectively ( P < or = 0.01). A decrease in inspiratory muscle function was observed at 9 wk post-IMT in DT. Inspiratory muscle function plateaued between 9 and 18 wk but remained above pre-IMT values. Group M retained the improvements in inspiratory muscle function. CONCLUSION These data support the notion of pressure-flow specificity of IMT. Detraining resulted in small but significant reductions in inspiratory muscle function. Reducing training frequency by two thirds allowed for the maintenance of inspiratory muscle function up to 18 wk post-IMT.

Effect of graded hypoxia on supraspinal contributions to fatigue with unilateral knee-extensor contractions

Supraspinal fatigue, defined as an exercise-induced decline in force caused by suboptimal output from the motor cortex, accounts for over one-quarter of the force loss after fatiguing contractions of the knee extensors in normoxia. We tested the hypothesis that the relative contribution of supraspinal fatigue would be elevated with increasing severities of acute hypoxia. On separate days, 11 healthy men performed sets of intermittent, isometric, quadriceps contractions at 60% maximal voluntary contraction to task failure in normoxia (inspired O(2) fraction/arterial O(2) saturation = 0.21/98%), mild hypoxia (0.16/93%), moderate hypoxia (0.13/85%), and severe hypoxia (0.10/74%). Electrical stimulation of the femoral nerve was performed to assess neuromuscular transmission and contractile properties of muscle fibers. Transcranial magnetic stimulation was delivered to the motor cortex to quantify corticospinal excitability and voluntary activation. After 10 min of breathing the test gas, neuromuscular function and cortical voluntary activation prefatigue were unaffected in any condition. The fatigue protocol resulted in ∼ 30% declines in maximal voluntary contraction force in all conditions, despite differences in time-to-task failure (24.7 min in normoxia vs. 15.9 min in severe hypoxia, P < 0.05). Potentiated quadriceps twitch force declined in all conditions, but the decline in severe hypoxia was less than that in normoxia (P < 0.05). Cortical voluntary activation also declined in all conditions, but the deficit in severe hypoxia exceeded that in normoxia (P < 0.05). The additional central fatigue in severe hypoxia was not due to altered corticospinal excitability, as electromyographic responses to transcranial magnetic stimulation were unchanged. Results indicate that peripheral mechanisms of fatigue contribute relatively more to the reduction in force-generating capacity of the knee extensors following submaximal intermittent isometric contractions in normoxia and mild to moderate hypoxia, whereas supraspinal fatigue plays a greater role in severe hypoxia.

Voluntary activation of human knee extensors measured using transcranial magnetic stimulation

The aim of this study was to determine the applicability and reliability of a transcranial magnetic stimulation twitch interpolation technique for measuring voluntary activation of a lower limb muscle group. Cortical voluntary activation of the knee extensors was determined in nine healthy men on two separate visits by measuring superimposed twitch torques evoked by transcranial magnetic stimulation during isometric knee extensions of varying intensity. Superimposed twitch amplitude decreased linearly with increasing voluntary torque between 50 and 100% of mean maximal torque, allowing estimation of resting twitch amplitude and subsequent calculation of voluntary activation. There were no systematic differences for maximal voluntary activation within day (mean ±s.d. 90.9 ± 6.2 versus 90.7 ± 5.9%; P= 0.98) or between days (90.8 ± 6.0 versus 91.2 ± 5.7%; P= 0.92). Systematic bias and random error components of the 95% limits of agreement were 0.23 and 9.3% within day versus−0.38 and 7.5% between days. Voluntary activation was also determined immediately after a 2 min maximal voluntary isometric contraction; in four of these subjects, voluntary activation was determined 30 min after the sustained contraction. Immediately after the sustained isometric contraction, maximal voluntary activation was reduced from 91.2 ± 5.7 to 74.2 ± 12.0% (P < 0.001), indicating supraspinal fatigue. After 30 min, voluntary activation had recovered to 85.4 ± 8.8% (P= 0.39 versus baseline). These results demonstrate that transcranial magnetic stimulation enables reliable measurement of maximal voluntary activation and assessment of supraspinal fatigue of the knee extensors.