Effects of expiratory threshold loading during steady-state exercise.

Increases in functional residual capacity (FRC) decrease inspiratory muscle efficiency; the present experiments were designed to determine the effect of FRC change on the ventilatory response to exercise. Six well-trained adults were exposed to expiratory threshold loads (ETL) ranging from 5 to 40 cmH2O during steady-state exercise on a bicycle ergometer at 40-95% VO2max. Inspiratory capacity (IC) was measured and changes of IC interpreted as changes of FRC. ETL did not consistently limit exercise performance. At heavy work (greater than 92% VO2max) minute ventilation decreased with increasing ETL; at moderate work (less than 58% VO2max) it did not. Decreases in ventilation were due to decreases in respiratory frequency with prolongation of the duration of expiration being the most consistent change in breathing pattern. At moderate work levels, FRC increased with ETL; at maximum work it did not. Changes in FRC were dictated by constancy of tidal volume and a fixed maximum end-inspiratory volume of 80-90% of the inspiratory capacity. When tidal volume was such that end-inspiratory volume was less than this value, FRC increased with ETL. Mouth pressure measured during the first 0-1 s of inspiratory effort against an occluded airway (P0-1) was increased by ETL equals 30 cmH2O, in spite of the fact that ventilation was decreased. We concluded that changes in FRC due to ETL had no effect on the ventilatory response to exercise and that changes in P0-1 induced by ETL did not reflect changes of inspiratory drive so much as changes of the pattern of inspiration.     

Synchronization of respiratory frequency by somatic afferent stimulation.

In cats anesthetized with chloralose-urethan, vagotomized, paralyzed, and artifically ventilated, superficial radial (cutaneous) and hamstring (muscle) nerve afferents were stimulated while phrenic nerve electrical activity was recorded. The results obtained with both types of nerves were similar. Stimulation in mid and late expiration advanced the onset of the next inspiration, shortening its duration. Stimulation in early inspiration advanced, while that in late inspiration delayed, the onset of the next expiration. These effects were often accompanied by changes in phrenic motoneuron firing patterns (earlier recruitment, increased discharge frequency, increased slope of integrated phrenic neurogram). Repetitive somatic afferent stimulation produced sustained increases in respiratory frequency in all cats and in half of them entrainment of respiratory frequency to the frequency of stimulation occurred at ratios such as 4:3, 4:5, 1:2, 1:3, 1:4, and 1:7. The lowest stimulus intensity required for evoking these phase shifts was between 5 and 10T (threshold of most excitable fibers) for muscle afferents and between 1 and 2T for cutaneous afferents. These results demonstrate the existence of a reflex mechanism capable of locking respiratory frequency to that of a periodic somatic afferent input. They also provide an experimental basis for the hypothesis that reflexes are resposible for the observed locking between step or pedal frequency and respiratory rate during exercise in man.     

Effects of separate rib cage and abdominal restriction on exercise performance in normal humans

We assessed the effects of selective restriction of movements of the rib cage (Res,rc) and abdomen (Res,ab) on ventilatory pattern, transdiaphragmatic pressure (Pdi), and electrical activity of the diaphragm (Edi) in five normal subjects exercising at a constant work rate (80% of maximum power output) on a cycle ergometer till exhaustion. Restriction of movements was achieved by an inelastic corset applied tightly around the rib cage or abdomen. Edi was recorded by an esophageal electrode, rectified, and then integrated, and peak values during inspiration were measured. Each subject exercised at the same work rate on 3 days: with Res,rc, with Res,ab, and without restriction (control). Res,rc but not Res,ab reduced exercise time (tlim). Up to tlim, minute ventilation (VE) was similar in all three conditions. At any level of VE, however, Res,rc decreased tidal volume and inspiratory and expiratory time, whereas Res,ab had no effect on the pattern of breathing. Res,ab was associated with higher inspiratory Pdi swings at any level of VE, whereas peak Edi was similar to control. Inspiratory Pdi swings were the same with Res,rc as control, but the peak Edi for a given Pdi was greater with Res,rc (P less than 0.05). During Res,rc the abdominal pressure swings in expiration were greater than with Res,ab and control. We conclude that Res,rc altered the pattern of breathing in normal subjects in high-intensity exercise, decreased diaphragmatic contractility, increased abdominal muscle recruitment in expiration, and reduced tlim. On the other hand, Res,ab had no effect on breathing pattern or tlim but was associated with increased diaphragmatic contractility.     

Time-dependent responses of expiration reflex in cats

We investigated the effectiveness of the "expiration reflex" in 10 anesthetized spontaneously breathing cats. The expiration reflex was produced by mechanical stimulation of the vocal folds and electrical stimulation of the superior laryngeal nerve at different moments in the respiratory cycle and at various levels of respiratory chemical drive. The effectiveness of the expiration reflex was evaluated from sudden changes in expiratory flow immediately following the stimulation. Both mechanical and electrical stimulations given during early inspiration caused little or no expiratory efforts, whereas stimulations given during early expiration or hypocapnic apnea produced a typical expiration reflex. Changes in arterial CO2 and O2 partial pressures influenced neither the relationships between the stimulation and its effect on the expiration reflex nor the strength of the expiration reflex. These results indicate that the timing of stimulation with relation to the phase of the respiratory cycle is critical to its effect on the expiration reflex and that changes in respiratory chemical drive do not modify the expiration reflex characteristics.     

Oxygen uptake/heart rate relationship in leg and arm exercise, sitting and standing.

The effect of leg exercise and of arm exercise in sitting and standing body positions on energy output and on some cardiorespiratory parameters was studied in seven male subjects. Oxygen uptake (VO2), heart rate (fH), pulmonary ventilation (VE) and respiratory frequency were measured at rest, in the 7-8th min of submaximal work (300, 600, 900 kpm/min), and at maximal effort. Significantly higher Vo2, fH, and VE in arm cranking than in cycling were found at submaximal work loads above 300 kpm/min. Though the maximal work load in arm exercise was 50-60% of that in cycling, Vo2 in arm work was at maximal effort only 22% lower than in leg exercise while the difference in fH was insignificant. No differences were found in arm work between the results obtained at any work level in sitting and standing body positions. The only postural difference in arm work was a 13% higher work load achieved at maximal effort when standing than when sitting. Differences in fH between arm and leg exercise were much smaller for the same Vo2 than for the same work load and were time dependent. While fH quickly leveled off in leg exercise, fH in arm cranking rose steadily during the first 6 min of work which created the fH differences observed in the 7-8 min of submaximal arm arm and leg exercise. At submaximal work levels a tendency to synchronize the respiratory frequency with the frequency of the rotatory movements was more apparent in arm cranking than in cycling.     

Effect of resistive loads on pattern of respiratory muscle recruitment during exercise.

In healthy subjects, we compared the effects of an expiratory (ERL) and an inspiratory (IRL) resistive load (6 cmH2O.l-1.s) with no added resistive load on the pattern of respiratory muscle recruitment during exercise. Fifteen male subjects performed three exercise tests at 40% of maximum O2 uptake: 1) with no-added-resistive load (control), 2) with ERL, and 3) with IRL. In all subjects, we measured breathing pattern and mouth occlusion pressure (P0.1) from the 3rd min of exercise, in 10 subjects O2 uptake (VO2), CO2 output (VCO2), and respiratory exchange ratio (R), and in 5 subjects we measured gastric (Pga), pleural (Ppl), and transdiaphragmatic (Pdi) pressures. Both ERL and IRL induced a high increase of P0.1 and a decrease of minute ventilation. ERL induced a prolongation of expiratory time with a reduction of inspiratory time (TI), mean expiratory flow, and ratio of inspiratory to total time of the respiratory cycle (TI/TT). IRL induced a prolongation of TI with a decrease of mean inspiratory flow and an increase of tidal volume and TI/TT. With ERL, in two subjects, Pga increased and Ppl decreased more during inspiration than during control suggesting that the diaphragm was the most active muscle. In one subject, the increases of Ppl and Pga were weak; thus Pdi increased very little. In the two other subjects, Ppl decreased more during inspiration but Pga also decreased, leading to a decrease of Pdi. This suggests a recruitment of abdominal muscles during expiration and of accessory and intercostal muscles during inspiration. With IRL, in all subjects, Ppl again decreased more, Pga began to decrease until 40% of TI and then increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of SO2 on control of breathing in anesthetized cats

In seven anesthetized tracheotomized cats we studied the acute respiratory effects of SO2 inhalation at different steady-state levels of arterial CO2 tension (Paco2). During room air breathing, SO2 (0.05%) addition caused a progressive reduction in tidal volume (VT) and increases in both respiratory frequency (f) and pulmonary resistance (RL). Atropine sulfate abolished the bronchoconstriction response to SO2 and thus permitted the study of the influence of SO2 on VT and f in the absence of constricted airways. Despite marked reductions in the VT VS. PaCO2 relationships with SO2 exposure after atropine, the relationship between pulmonary ventilation (VE) and PaCO2 was not signifcantly altered. This was the case since SO2 caused solely a reduction in inspiratory duration (Ti), affecting neither the mean rate of rise of inspiratory activity (i.e., VT/Ti) nor the relationship between Ti and breath duration. Thus, airways irritation with SO2 produced rapid, shallow breathing characterized by a shortening of inspiratory and total respiratory cycle times with no change in the rate of development of inspiratory activity. The findings suggest an influence exclusively concerned with the timing of inspiration. Perhaps premature onset of inspiratory activity accounts for the observed effects.     

Effect of anaesthesia on the pattern of breathing.

The pattern of breathing of male rats was studied after stimulating respiration with carbon dioxide at different levels of general anaesthesia. Anaesthesia was induced by the inhalation of halothane or by the i.p. injection of urethane. Ventilation values were measured in intubated rats in body plethysmograph. It was found that a linear relationship between minute ventilation and tidal volume was maintained during the decrease of minute ventilation due to deepening of anaesthesia. The slope of the relationship after stimulating respiration with carbon dioxide also diminished during deeper anaesthesia. The duration of inspiration did not alter significantly, despite marked changes in tidal volume. Tidal volume correlated with the duration of expiration at different anaesthesia levels. In vagotomized rats, the duration of expiration shortened as ventilation was depressed by deepening anaesthesia.     

Changes of respiratory input impedance during breathing in humans.

Changes of total respiratory resistance (Rrs) and reactance (Xrs) were studied between 8 and 32 Hz at five moments during the respiratory cycle in healthy adults (group A) and children (group B) and in patients with chronic obstructive lung disease (group C) and with upper airway obstruction (group D). Two forced oscillation techniques were used: the conventional one and the head generator, with the oscillations applied at the mouth and around the head of the subject, respectively. Both techniques yielded similar results. Rrs is lowest during the transition from inspiration to expiration and highest in the course of expiration, except in group D. Mean Xrs is highest at the transitions from inspiration to expiration or vice versa and lowest during expiration, except in group D. In groups C and D, the increases of Rrs are accompanied by a more pronounced negative frequency dependence of Rrs. The variations of Rrs and Xrs appear to be markedly flow dependent and may be a consequence of the interaction of breathing with oscillatory flows.     

A Closed-Loop Model of the Respiratory System: Focus on Hypercapnia and Active Expiration

Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. During quiet breathing, pumping air from the lungs is mostly performed by contraction of the diaphragm during inspiration, and muscle contraction during expiration does not play a significant role in ventilation. In contrast, during intense exercise or severe hypercapnia forced or active expiration occurs in which the abdominal “expiratory” muscles become actively involved in breathing. The mechanisms of this transition remain unknown. To study these mechanisms, we developed a computational model of the closed-loop respiratory system that describes the brainstem respiratory network controlling the pulmonary subsystem representing lung biomechanics and gas (O₂ and CO₂) exchange and transport. The lung subsystem provides two types of feedback to the neural subsystem: a mechanical one from pulmonary stretch receptors and a chemical one from central chemoreceptors. The neural component of the model simulates the respiratory network that includes several interacting respiratory neuron types within the Bötzinger and pre-Bötzinger complexes, as well as the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) representing the central chemoreception module targeted by chemical feedback. The RTN/pFRG compartment contains an independent neural generator that is activated at an increased CO₂ level and controls the abdominal motor output. The lung volume is controlled by two pumps, a major one driven by the diaphragm and an additional one activated by abdominal muscles and involved in active expiration. The model represents the first attempt to model the transition from quiet breathing to breathing with active expiration. The model suggests that the closed-loop respiratory control system switches to active expiration via a quantal acceleration of expiratory activity, when increases in breathing rate and phrenic amplitude no longer provide sufficient ventilation. The model can be used for simulation of closed-loop control of breathing under different conditions including respiratory disorders.     

Breathing during exercise in subjects with mild-to-moderate airflow obstruction: effects of physical training.

In this study we explored the effects of physical training on the response of the respiratory system to exercise. Eight subjects with irreversible mild-to-moderate airflow obstruction [forced expiratory volume in 1 s of 85 +/- 14 (SD) % of predicted and ratio of forced expiratory volume in 1 s to forced vital capacity of 68 +/- 5%] and six normal subjects with similar anthropometric characteristics underwent a 2-mo physical training period on a cycle ergometer three times a week for 31 min at an intensity of approximately 80% of maximum heart rate. At this work intensity, tidal expiratory flow exceeded maximal flow at control functional residual capacity [FRC; expiratory flow limitation (EFL)] in the obstructed but not in the normal subjects. An incremental maximum exercise test was performed on a cycle ergometer before and after training. Training improved exercise capacity in all subjects, as documented by a significant increase in maximum work rate in both groups (P < 0.001). In the obstructed subjects at the same level of ventilation at high workloads, FRC was greater after than before training, and this was associated with an increase in breathing frequency and a tendency to decrease tidal volume. In contrast, in the normal subjects at the same level of ventilation at high workloads, FRC was lower after than before training, so that tidal volume increased and breathing frequency decreased. These findings suggest that adaptation to breathing under EFL conditions does not occur during exercise in humans, in that obstructed subjects tend to increase FRC during exercise after experiencing EFL during a 2-mo strenuous physical training period.     

The effect of training on endurance and the cardiovascular responses of individuals with paraplegia during dynamic exercise induced by functional electrical stimulation

Endurance for dynamic exercise, cardiac output, blood pressure, heart rate, ventilation, and oxygen consumption was measured in eight individuals with paraplegia at the end of 4-min bouts of exercise on a friction braked cycle ergometer. Movement of the subjects' legs was induced by electrically stimulating the quadriceps, gluteus maximus and hamstring muscles with a computer-controlled biphasic square--wave current at a frequency of 30 Hz. The friction braked cycle ergometer was pedalled at work rates which varied between 0 and 40 W. Measurements were repeated after 3 and 6 months to assess the affect of training. After 3 months of training it was found that endurance increased from 8 min at a work rate of 0 W to 30 min at a work rate of 40 W. Compared to the cardiovascular responses in non-paralyzed subjects, computerized cycle ergometry was found to be associated with higher relative stresses for a given level of absolute work. Mean blood pressure, for example, increased by over 30% during maximal work in individuals with paralysis compared to the typical response obtained for able-bodied subjects. Analysis of the data showed that instead of the 20-30% metabolic efficiency commonly reported for cycle ergometry, the calculated metabolic efficiency during computer-controlled cycle ergometry was only 3.6%.     

Ventilatory control during exercise with increased external dead space

Effects of increased external dead space (VD) on ventilatory control in steady-state exercise were determined in three healthy adults. The subjects performed cycle ergometer exercise on six occasions, each with a different VD (range: 0.1--1.0 liter); work rate was incremented every 5 min by 15--20 W. Minute ventilation (VE), CO2 output (VCO2), and mean alveolar PCO2 (PACO2) were measured in the steady state. Without VD, the VE-VCO2 relationship was linear, having a small positive VE intercept, and PACO2 was constant, independent of VCO2. Increased VD was associated with an upward shift of the VE-VCO2 relationship, and an elevated PACO2, again independent of VCO2. At each work rate, the increases in VE accompanying increased VD were no greater than could be expected from a conventional CO2 inhalation study. It is concluded that increasing external dead space does not impair the ability of the human respiratory system to regulate PACO2 during exercise except for resetting the regulated PCO2 level.     

A system to simulate gas exchange in humans to control quality of metabolic measurements

We have developed a gas exchange simulation system (GESS) to assess the quality control in measurements of metabolic gas exchange. The GESS simulates human breathing from rest to maximal exercise. It approximates breath-by-breath waveforms, ventilatory output, gas concentrations, temperature and humidity during inspiration and expiration. A programmable motion control driving two syringes allows the ventilation to be set at any tidal volume (V _T), respiratory frequency (f), flow waveform and period of inspiration and expiration. The GESS was tested at various combinations of V _T (0.5–2.5 l) and f (10–60 stroke · min⁻¹) and at various fractional concentrations of expired oxygen (0.1294–0.1795); and carbon dioxide (0.0210–0.0690) for a pre-set flow waveform and for expired gases at the same temperature and humidity as room air. Expired gases were collected in a polyethylene bag for measurement of volume and gas concentrations. Accuracy was assessed by calculating the absolute and relative errors on parameters (error = measured−predicted). The overall error in the gas exchange values averaged less than 2% for oxygen uptake and carbon dioxide output, which is within the accuracy of the Douglas bag method. Accepted: 4 June 1998     

Sinoaortic contribution to ventilatory control in exercising dogs

The role of the sinoaortic reflexes in the regulation of ventilation during exercise was evaluated in seven awake dogs prepared with chronic tracheostomies and arterial catheters. Each dog ran on a treadmill at several work loads before and after sinoaortic denervation and served as its own control. Minute ventilation in the sinoaortic denervated state was significantly reduced from intact values by 10-40% at the mild and moderate levels of exercise [O2 uptake (VO2) = 30-50 ml . kg-1 . min-1] mainly as a result of a lowering respiratory frequency. At higher work loads (VO2 = 70-80 ml . kg-1 . min-1) minute ventilation was similar in the intact and denervated states, but the pattern of ventilation was altered with a higher frequency and a lower tidal volume in the denervated state. The rise in ventilation toward a stable plateau was slower at all work loads in the denervated than in the intact state. After sinoaortic denervation, arterial PCO2(PaCO2) levels were significantly elevated above intact PaCO2 levels during both the preexercise period and the steady state at all exercise levels. These results suggest that the sinoaortic reflexes contribute to both the control of ventilation and the pattern of breathing during mild and heavy levels of exercise in the conscious dog.     

Function of brainstem neurons in optimal control of respiratory mechanics

An optimization control procedure is developed to describe the function of the human respiratory controller in determination of the respiratory frequency, the expiratory reserve volume, and the physiological dead space volume at all levels of human activity. The required level of alveolar ventilation is considered to have been determined based on the inputs from the peripheral and central chemoreceptors. The proposed procedure describes the mechanical control of breathing in which the excitation signals are adjusted and transferred from the neuron pools in the brainstem to the respiratory muscles to control the rate and depth of breathing. The criterion of minimum average respiratory work rate is used to find the optimal characteristics of respiration. The respiratory frequency, physiologic dead space volume, and expiratory reserve volume are used simultaneously as the optimization variables to minimize the average respiratory work rate. The optimization procedure has been applied by using different airflow patterns at various levels of ventilation. The theoretical results of the study have been compared with the experimental data in exercise taken from the literature. The results show a close agreement between the experimentally measured data and the theoretical values found by the optimization control procedure. The findings attest to the validity of the minimum average work rate criterion and the proposed multivariable optimization procedure compared with other procedures suggested in the literature in control of respiratory mechanics.     

The breathing pattern after breath-holding: the influence of chest position and the drive to breathe.

The pattern of breathing following the breaking-point of sixty breath-holds has been studied in five healthy adults and compared with the pattern during recovery from CO2-rebreathing. The volume and direction of the first respiratory movement, and the VT, V relation for the first four complete breaths was measured. Only when breath-holds were terminated with an inspiration was the accumulated drive to breathe reflected in an increased volume of the first respiratory movement: terminating expirations simply returned the chest to the resting respiratory level. The volume of the first inspiration was not influenced by the intervention of a terminating expiration, suggesting that expiratory movements do not dissipate the non-chemical component of the drive to breathe. In three of the five subjects the tidal volumes for given levels of ventilation were greater following breath-holding than following rebreathing. This altered pattern of breathing has been interpreted in terms of an insiratory-augmenting reflex.     

Effects of bronchoconstriction and external resistive loading on the sensation of dyspnea.

To determine whether the intensity of dyspnea at a given level of respiratory motor output differs between bronchoconstriction and the presence of an external resistance, we compared the sensation of difficulty in breathing during isocapnic voluntary hyperventilation in six normal subjects. An external resistance of 1.9 cmH2O.1-1.s was applied during both inspiration and expiration. To induce bronchoconstriction, histamine aerosol (5 mg/ml) was inhaled until airway resistance (Raw) increased to a level approximately equal to the subject's control Raw plus the added external resistance. To clarify the role of vagal afferents on the genesis of dyspnea during both forms of obstruction to airflow, the effect of airway anesthesia by lidocaine aerosol inhalation was also examined after histamine and during external resistive loading. The sensation of difficulty in breathing was rated at 30-s intervals on a visual analog scale during isocapnic voluntary hyperpnea, in which the subjects were asked to copy an oscilloscope volume trace obtained previously during progressive hypercapnia. Histamine inhalation significantly increased the intensity of the dyspneic sensation over the equivalent external resistive load at the same levels of ventilation and occlusion pressure during voluntary hyperpnea. Inhaled lidocaine decreased the sensation of dyspnea during bronchoconstriction with no change in Raw, but it did not significantly change the sensation during external resistive loading. These results suggest that afferent vagal activity plays a role in the genesis of dyspnea during bronchoconstriction.     

Effect of cold air inhalation on core temperature in exercising subjects under heat stress

Whether increasing respiratory heat loss (RHL) during exercise under heat stress can contain elevation of rectal temperature (Tre) was examined. Eight men cycled twice at 45-50% their maximum work rate until exhaustion at ambient temperature and relative humidity of 38 degrees C and 90-95%, respectively. They inspired either cold (3.6 degrees C) or ambient air in random sequence. When subjects breathed cold air during 23 min of exercise, a ninefold increase in RHL was observed vs. similar work during hot air inhalation (32.81 vs. 3.46 W). Respiratory frequency (f) and rate of rise in Tre decreased significantly (P less than or equal to 0.004 and P less than or equal to 0.002, respectively). The rise in skin temperature in each inhalant gas condition was accompanied by a parallel almost equal increase in core temperature above basal (delta Tre) for equivalent gains in skin temperature. The increase in tidal volume and decreased f in the cold condition allowed more effective physical conditioning of cold inspirate gas in the upper airways and aided RHL. Cold air inhalation also produced a significant (P less than or equal to 0.05) decrease in heart rate vs. hot air inhalation in the final stages of exercise. Insignificant changes in O2 consumption and total body fluid loss were found. These data show that cold air inhalation during exercise diminishes elevation of Tre and suggest that both the intensity and duration of work can thus be extended. The importance of the physical exchange of heat energy and any physiological mechanisms induced by the cold inspirate in producing the changes is undetermined.