Gregory M. Blain

Group III and IV muscle afferents contribute to ventilatory and cardiovascular response to rhythmic exercise in humans

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.

Implications of group III and IV muscle afferents for high‐intensity endurance exercise performance in humans

Non‐Technical Summary  We investigated the influence of group III/IV muscle afferents on central motor drive, the development of peripheral locomotor muscle fatigue, and endurance performance time during high‐intensity constant‐load cycling exercise to exhaustion. Our findings suggest that, on the one hand, afferent feedback ensures adequate circulatory and ventilatory responses to exercise which optimizes muscle O2 transport and thereby facilitates exercise performance by preventing premature peripheral fatigue. On the other hand, afferent feedback inhibits central motor drive, which is reflected in the restriction of the neural excitation of the locomotor musculature and the reduced tolerance for peripheral muscle fatigue, and thereby limits exercise performance. Taken together, the current investigation revealed the net effects of sensory afferent feedback on time to exhaustion during high‐intensity constant‐load cycling exercise and showed that intact group III/IV muscle afferent feedback is a vital component in achieving optimal endurance performance.

Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO2

We assessed the contribution of carotid body chemoreceptors to the ventilatory response to specific CNS hypercapnia in eight unanaesthetized, awake dogs. We denervated one carotid body (CB) and used extracorporeal blood perfusion of the reversibly isolated remaining CB to maintain normal CB blood gases (normoxic, normocapnic perfusate), to inhibit (hyperoxic, hypocapnic perfusate) or to stimulate (hypoxic, normocapnic perfusate) the CB chemoreflex, while the systemic circulation, and therefore the CNS and central chemoreceptors, were exposed consecutively to four progressive levels of systemic arterial hypercapnia via increased fractional inspired CO2 for 7 min at each level. Neither unilateral CB denervation nor CB perfusion, per se, affected breathing. Relative to CB control conditions (normoxic, normocapnic perfusion), we found that CB chemoreflex inhibition decreased the slope of the ventilatory response to CNS hypercapnia in all dogs to an average of 19% of control values (range 0–38%; n= 6), whereas CB chemoreflex stimulation increased the slope of the ventilatory response to CNS hypercapnia in all dogs to an average of 223% of control values (range 204–235%; n= 4). We conclude that the gain of the CNS CO2/H+ chemoreceptors in dogs is critically dependent on CB afferent activity and that CNS–CB interaction results in hyperadditive ventilatory responses to central hypercapnia.

An interdependent model of central/peripheral chemoreception: evidence and implications for ventilatory control.

In this review we discuss the implications for ventilatory control of newer evidence suggesting that central and peripheral chemoreceptors are not functionally separate but rather that they are dependent upon one another such that the sensitivity of the medullary chemoreceptors is critically determined by input from the carotid body chemoreceptors and vice versa i.e., they are interdependent. We examine potential interactions of the interdependent central and carotid body (CB) chemoreceptors with other ventilatory-related inputs such as central hypoxia, lung stretch, and exercise. The limitations of current approaches addressing this question are discussed and future studies are suggested.

Role of Central/Peripheral Chemoreceptors and Their Interdependence in the Pathophysiology of Sleep Apnea

Unstable periodic breathing with intermittent ventilatory overshoots and undershoots commonly occurs in chronic heart failure, in hypoxia, with chronic opioid use and in certain types of obstructive sleep apnea. Sleep promotes breathing instability because it unmasks a highly sensitive dependence of the respiratory control system on chemoreceptor input, because transient cortical arousals promote ventilatory overshoots and also because upper airway dilator muscle tonicity is reduced and airway collapsibility enhanced. We will present data in support of the premise that carotid chemoreceptors are essential in the pathogenesis of apnea and periodicity; however it is the hyperadditive influence of peripheral chemoreceptor sensory input on central chemosensitivity that accounts for apnea and periodic breathing. This chemoreceptor interdependence also provides a significant portion of the normal drive to breathe in normoxia (i.e. eupnea) and in acute hypoxia. Finally, we discuss the effects of preventing transient hypocapnia (via selective increases in FICO(2)) on centrally mediated types of periodic breathing and even some varieties of cyclical obstructive sleep apnea.

Contribution of the carotid body chemoreceptors to eupneic ventilation in the intact, unanesthetized dog

We used extracorporeal perfusion of the reversibly isolated carotid sinus region to determine the effects of specific carotid body (CB) chemoreceptor inhibition on eupneic ventilation (Vi) in the resting, awake, intact dog. Four female spayed dogs were studied during wakefulness when CB was perfused with 1) normoxic, normocapnic blood; and 2) hyperoxic (>500 mmHg), hypocapnic ( approximately 20 mmHg) blood to maximally inhibit the CB tonic activity. We found that CB perfusion per se (normoxic-normocapnic) had no effect on Vi. CB inhibition caused marked reductions in Vi (-60%, range 49-80%) and inspiratory flow rate (-58%, range 44-87%) 24-41 s following the onset of CB perfusion. Thereafter, a partial compensatory response was observed, and a steady state in Vi was reached after 50-76 s following the onset of CB perfusion. This steady-state tidal volume-mediated hypoventilation ( approximately 31%) coincided with a significant reduction in mean diaphragm electromyogram (-24%) and increase in mean arterial pressure (+12 mmHg), which persisted for 7-25 min until CB perfusion was stopped, despite a substantial increase in CO(2) retention (+9 Torr, arterial Pco(2)) and systemic respiratory acidosis. We interpret these data to mean that CB chemoreceptors contribute more than one-half to the total eupneic drive to breathe in the normoxic, intact, awake animal. We speculate that this CB contribution consists of both the normal tonic sensory input from the CB chemoreceptors to medullary respiratory controllers, as well as a strong modulatory effect on central chemoreceptor responsiveness to CO(2).

Exercise performance is regulated during repeated sprints to limit the development of peripheral fatigue beyond a critical threshold

What is the central question of this study? We asked whether exercise performance is regulated during all‐out repeated sprints (involving peak cycling‐specific muscle activation and limited pacing strategy) in order to restrain the total degree of peripheral fatigue development. What is the main finding and its importance? Our results showed that power output is adjusted during repeated sprints to limit the development of peripheral fatigue to a critical threshold, independently of the degree of pre‐existing fatigue. These findings emphasize the important role of peripheral fatigue in adjustment of power output during exercise.

Time-frequency analysis of heart rate variability reveals cardiolocomotor coupling during dynamic cycling exercise in humans

To test the hypothesis that cycling exercise modulates heart rate variability (HRV), we applied a short-time Fourier transform on the electrocardiogram of subjects performing a maximal graded cycling test. A pedaling frequency component (PFC) in HRV was continuously observed over the time course of the exercise test and extracted from R-R interval series obtained from 15 healthy subjects with a heterogeneous physical fitness, exercising at three different pedaling frequency (n = 5): 70, 80, and 90 rpm. From 30 to 50% of the maximal power output (P(max)), in the 90 rpm group, spectral aliasing caused PFC to overlap with the respiratory sinus arrhythmia (RSA) band, significantly overestimating the PFC amplitude (A(PFC)). In the meantime, A(PFC) did not increase significantly from its minimal values in the 70 rpm ( approximately 1.26 ms) and 80 rpm ( approximately 1.20 ms) groups. Then, from 60 to 100% maximal power output (P(max)), workload increase caused a significant approximately 2.8-, approximately 3.3-, and approximately 3.4-fold increase in A(PFC) in the 70, 80, and 90 rpm groups, respectively, with no significant difference between groups. At peak exercise, A(PFC) accounted for approximately 43, approximately 39, and approximately 49% of the total HRV in the 70, 80, and 90 rpm groups, respectively. Our findings indicate that cycling continuously modulates the cardiac chronotropic response to exercise, inducing a new component in HRV, and that workload increase during intense exercise further accentuates this cardiolocomotor coupling. Moreover, because PFC and RSA overlapped at low workloads, methodological care should be taken in future studies aiming to quantify RSA as an index of parasympathetic activity.

Time-varying analysis methods and models for the respiratory and cardiac system coupling in graded exercise

The analysis of heart period series is a difficult task especially under graded exercise conditions. From all the information present in these series, we are the most interested in the coupling between respiratory and cardiac systems, known as respiratory sinus arrythmia. In this paper, we show that precise patterns concerning the respiratory frequency can be extracted from the heart period series. An evolutive model is introduced in order to achieve tracking of the main respiratory-related frequencies and their time-varying amplitudes. Since respiration acts to modulate the sinus rhythm, we relate the frequencies and amplitudes to this modulation by analyzing in detail its nonlinear transformation giving the heart period signal. This analysis is performed assuming stationary conditions but also in the realistic case where the mean heart period, the amplitude, and the frequency of the respiration are time-varying. Since this paper is devoted to the theoretical and complete presentation of the method used in a physiological study published elsewhere, the capabilities of our method will be illustrated in a realistic simulated case.

Assessment of ventilatory thresholds during graded and maximal exercise test using time varying analysis of respiratory sinus arrhythmia

Objective: To test whether ventilatory thresholds, measured during an exercise test, could be assessed using time varying analysis of respiratory sinus arrhythmia frequency (fRSA). Methods: Fourteen sedentary subjects and 12 endurance athletes performed a graded and maximal exercise test on a cycle ergometer: initial load 75 W (sedentary subjects) and 150 W (athletes), increments 37.5 W/2 min. fRSA was extracted from heart period series using an evolutive model. First (TV1) and second (TV2) ventilatory thresholds were determined from the time course curves of ventilation and ventilatory equivalents for O2 and CO2. Results:fRSA was accurately extracted from all recordings and positively correlated to respiratory frequency (r = 0.96 (0.03), p<0.01). In 21 of the 26 subjects, two successive non-linear increases were determined in fRSA, defining the first (TRSA1) and second (TRSA2) fRSA thresholds. When expressed as a function of power, TRSA1 and TRSA2 were not significantly different from and closely linked to TV1 (r = 0.99, p<0.001) and TV2 (r = 0.99, p<0.001), respectively. In the five remaining subjects, only one non-linear increase was observed close to TV2. Significant differences (p<0.04) were found between athlete and sedentary groups when TRSA1 and TRSA2 were expressed in terms of absolute and relative power and percentage of maximal aerobic power. In the sedentary group, TRSA1 and TRSA2 were 150.3 (18.7) W and 198.3 (28.8) W, respectively, whereas in the athlete group TRSA1 and TRSA2 were 247.3 (32.8) W and 316.0 (28.8) W, respectively. Conclusions: Dynamic analysis of fRSA provides a useful tool for identifying ventilatory thresholds during graded and maximal exercise test in sedentary subjects and athletes.