Ventilatory response of peripheral chemoreceptors to hypercapnia during exercise above the respiratory compensation point.

Peripheral hypercapnic chemosensitivity (PHC) is assessed as the change in ventilation in response to a rapid change in carbon dioxide pressures (Pco2). The increase in chemoresponse from rest to subrespiratory compensation point (RCP) exercise intensities is well-defined but less clear at intensities above the RCP when changes in known ventilatory stimulants occur. Twenty healthy subjects (n = 10 females) completed a maximal exercise test on 1 day, and on a subsequent day, transient hypercapnia was used to test PHC at multiple exercise stages. The transient hypercapnia involved two breaths of 10% CO2 repeated five times during each of the following: sitting at rest on the cycle ergometer, cycling at 40% wmax, cycling at 85% Wmax, at rest on the cycle ergometer immediately following the 85% stage, and cycling at 40% Wmax again following the postexercise rest. The PHC was not different across exercise intensities (0.98 ± 0.37 vs. 0.91 ± 0.39 vs. 0.92 ± 0.42 L·min-1·mmHg-1 for first 40% wmax, 85% wmax and second 40% Wmax, respectively (P = 0.45). There were no differences in PHC between presupra-RCP exercise rest and postsupra-RCP exercise rest (0.52 ± 0.23 vs. 0.53 ± 0.24 L·min-1·mmHg-1, P = 0.8003). Using a repeated-measures correlation to account for within-participant changes, there was a significant relationship between the end-tidal Pco2 and PHC for the 85% intensity (r = 0.5, P < 0.0001) when end-tidal Pco2 was dynamic between the trials. We conclude that the physiological changes (e.g., metabolic milieu and temperature) produced with supra-RCP exercise do not further augment PHC, and that the prestimulus end-tidal Pco2 modulates the PHC.NEW & NOTEWORTHY Exercise at intensities above the respiratory compensation point did not further augment peripheral hypercapnic chemosensitivity (PHC). Moreover, the PHC was not different during a preexercise resting state compared with rest immediately after intense exercise. The lack of differences across both comparisons suggests that exercise itself appears to sensitize the PHC.

The muscle reflex and chemoreflex interaction: ventilatory implications for the exercising human.

We examined the interactive influence of the muscle reflex (MR) and the chemoreflex (CR) on the ventilatory response to exercise. Eleven healthy subjects (5 women/6 men) completed three bouts of constant-load single-leg knee-extension exercise in a control trial and an identical trial conducted with lumbar intrathecal fentanyl to attenuate neural feedback from lower-limb group III/IV muscle afferents. The exercise during the two trials was performed while breathing ambient air ([Formula: see text] ~97%, [Formula: see text]~84 mmHg, [Formula: see text] ~32 mmHg, pH ~7.39), or under normocapnic hypoxia ([Formula: see text] ~79%, [Formula: see text] ~43 mmHg, [Formula: see text] ~33 mmHg, pH ~7.39) or normoxic hypercapnia ([Formula: see text] ~98%, [Formula: see text] ~105 mmHg, [Formula: see text] ~50 mmHg, pH ~7.26). During coactivation of the MR and the hypoxia-induced CR (O2-CR), minute ventilation (V̇e) and tidal volume (VT) were significantly greater compared with the sum of the responses to the activation of each reflex alone; there was no difference between the observed and summated responses in terms of breathing frequency (fB; P = 0.4). During coactivation of the MR and the hypercapnia-induced CR (CO2-CR), the observed ventilatory responses were similar to the summated responses of the reflexes (P ≥ 0.1). Therefore, the interaction between the MR and the O2-CR exerts a hyperadditive effect on V̇e and VT and an additive effect on fB, whereas the interaction between the MR and the CO2-CR is simply additive for all ventilatory parameters. These findings reveal that the MR:CR interaction further augments the ventilatory response to exercise in hypoxia.NEW & NOTEWORTHY Although the muscle reflex and the chemoreflex are recognized as independent feedback mechanisms regulating breathing during exercise, the ventilatory implications resulting from their interaction remain unclear. We quantified the individual and interactive effects of these reflexes during exercise and revealed differential modes of interaction. Importantly, the reflex interaction further amplifies the ventilatory response to exercise under hypoxemic conditions, highlighting a potential mechanism for optimizing arterial oxygenation in physically active humans at high altitude.

Optimizing Interval Training Through Power-Output Variation Within the Work Intervals.

PURPOSE: Maximal oxygen uptake (V˙O2max) is a key determinant of endurance performance. Therefore, devising high-intensity interval training (HIIT) that maximizes stress of the oxygen-transport and -utilization systems may be important to stimulate further adaptation in athletes. The authors compared physiological and perceptual responses elicited by work intervals matched for duration and mean power output but differing in power-output distribution. METHODS: Fourteen cyclists (V˙O2max 69.2 [6.6] mL·kg-1·min-1) completed 3 laboratory visits for a performance assessment and 2 HIIT sessions using either varied-intensity or constant-intensity work intervals. RESULTS: Cyclists spent more time at >90%V˙O2max during HIIT with varied-intensity work intervals (410 [207] vs 286 [162] s, P = .02), but there were no differences between sessions in heart-rate- or perceptual-based training-load metrics (all P ≥ .1). When considering individual work intervals, minute ventilation (V˙E) was higher in the varied-intensity mode (F = 8.42, P = .01), but not respiratory frequency, tidal volume, blood lactate concentration [La], ratings of perceived exertion, or cadence (all F ≤ 3.50, ≥ .08). Absolute changes (Δ) between HIIT sessions were calculated per work interval, and Δ total oxygen uptake was moderately associated with ΔV˙E (r = .36, P = .002). CONCLUSIONS: In comparison with an HIIT session with constant-intensity work intervals, well-trained cyclists sustain higher fractions of V˙O2max when work intervals involved power-output variations. This effect is partially mediated by an increased oxygen cost of hyperpnea and not associated with a higher [La], perceived exertion, or training-load metrics.

Coupling of dyspnea perception and occurrence of tachypnea during exercise.

During exercise, tidal volume initially contributes to ventilatory responses more than respiratory frequency, and respiratory frequency then increases rapidly while tidal volume stabilizes. Dyspnea intensity is also known to increase in a threshold-like manner. We tested the possibility that the threshold of tachypneic breathing is equal to that of dyspnea perception during cycle ergometer exercise (n = 27). Dyspnea intensity was scored by a visual analog scale. Thresholds were expressed as values of pulmonary O2 uptake at each breakpoint. Dyspnea intensity and respiratory frequency started increasing rapidly once the intensity of stimuli exceeded a threshold level. The thresholds for dyspnea intensity and for occurrence of tachypnea were significantly correlated. An intraclass correlation coefficient of 0.71 and narrow limits of agreement on the Bland-Altman plot indicated a good agreement between these thresholds. These results suggest that the start of tachypneic breathing coincides with the threshold for dyspnea intensity during cycle ergometer exercise.

Sciatic nerve stimulation activates the retrotrapezoid nucleus in anesthetized rats.

Retrotrapezoid nucleus (RTN) neurons sustain breathing automaticity. These neurons have chemoreceptor properties, but their firing is also regulated by multiple synaptic inputs of uncertain function. Here we test whether RTN neurons, like neighboring presympathetic neurons, are excited by somatic afferent stimulation. Experiments were performed in Inactin-anesthetized, bilaterally vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats. End-expiratory CO2 (eeCO2) was varied between 4% and 10% to modify rate and amplitude of phrenic nerve discharge (PND). RTN and presympathetic neurons were recorded extracellularly below the facial motor nucleus with established criteria. Sciatic nerve stimulation (SNstim, 1 ms, 0.5 Hz) slightly increased blood pressure (6.6 ± 1.6 mmHg) and heart rate and, at low eeCO2 (<5.5%), entrained PND. Ipsi- and contralateral SNstim produced the known biphasic activation of presympathetic neurons. SNstim evoked a similar but weaker biphasic response in up to 67% of RTN neurons and monophasic excitation in the rest. At low eeCO2, RTN neurons were silent and responded more weakly to SNstim than at high eeCO2 RTN neuron firing was respiratory modulated to various degrees. The phasic activation of RTN neurons elicited by SNstim was virtually unchanged at high eeCO2 when PND entrainment to the stimulus was disrupted. Thus RTN neuron response to SNstim did not result from entrainment to the central pattern generator. Overall, SNstim shifted the relationship between RTN firing and eeCO2 upward. In conclusion, somatic afferent stimulation increases RTN neuron firing probability without altering their response to CO2. This pathway may contribute to the hyperpnea triggered by nociception, exercise (muscle metabotropic reflex), or hyperthermia.

Type III-IV muscle afferents are not required for steady-state exercise hyperpnea in healthy subjects and patients with COPD or heart failure.

Blockade of group III-IV muscle afferents by intrathecal injection of the µ-opioid agonist fentanyl (IF) in humans has been variously reported to depress exercise hyperpnea in some studies but not others. A key unanswered question is whether such an effect is transient or persists in the steady state. Here we show that in healthy subjects undergoing constant-load cycling exercise IF significantly slows the transient exercise ventilatory kinetics but has no discernible effect on the ventilatory response when exercise is sufficiently prolonged. Thus, the ventilatory response to group III-IV muscle afferents input in healthy subjects is not a simple reflex but acts like a high-pass filter with maximum sensitivity during early-phase exercise and is reset in the late phase. In patients with chronic heart failure (CHF) IF causes sustained CO2 retention not only during exercise but also in the resting state, where muscle afferents feedback is minimal. In patients with chronic obstructive pulmonary disease (COPD), IF also elicits sustained decreases in the exercise ventilatory response but with little or no resultant CO2 retention due to concomitant decreases in physiological VD/VT (dead space-to-ventilation ratio). These results support the proposition that optimal long-term regulation of exercise hyperpnea in health and in disease is determined centrally by the respiratory controller through the continuing adaptation of an internal model which dynamically tracks the metabolic CO2 load and the ventilatory inefficiency 1/1-VD/VT that must be overcome for the maintenance of arterial PCO2 homeostasis, rather than being reflexively driven by group III-IV muscle afferents feedback per se.

Assessment of EIB: What you need to know to optimize test results.

Respiratory symptoms and asthma control questionnaires are poor predictors of the presence or severity of exercise-induced bronchoconstriction (EIB), and objective measurement is recommended. To optimize the chance of a positive test result, there are several factors to consider when exercising patients for EIB, including the ventilation achieved and sustained during exercise, water content of the inspired air, and the natural variability of the response. The high rate of negative exercise test results has led to the development of surrogates to identify EIB in laboratory or office settings, including eucapnic voluntary hyperpnea of dry air and inhalation of hyperosmolar aerosols.

Clinical consequences of altered chemoreflex control.

Control of ventilation dictates various breathing patterns. The respiratory control system consists of a central pattern generator and several feedback mechanisms that act to maintain ventilation at optimal levels. The concept of loop gain has been employed to describe its stability and variability. Synthesizing all interactions under a general model that could account for every behavior has been challenging. Recent insight into the importance of these feedback systems may unveil therapeutic strategies for common ventilatory disturbances. In this review we will address the major mechanisms that have been proposed as mediators of some of the breathing patterns in health and disease that have raised controversies and discussion on ventilatory control over the years.

Obesity: challenges to ventilatory control during exercise--a brief review.

Obesity is a national health issue in the US. Among the many physiological changes induced by obesity, it also presents a unique challenge to ventilatory control during exercise due to increased metabolic demand of moving larger limbs, increased work of breathing due to extra weight on the chest wall, and changes in breathing mechanics. These challenges to ventilatory control in obesity can be inconspicuous or overt among obese adults but for the most part adaptation of ventilatory control during exercise in obesity appears remarkably unnoticed in the majority of obese people. In this brief review, the changes to ventilatory control required for maintaining normal ventilation during exercise will be examined, especially the interaction between respiratory neural drive and ventilation. Also, gaps in our current knowledge will be discussed.