The pattern of breathing during hypoxic exercise

Breathing pattern was studied in six subjects in normoxia (FIO2 = 0.21) and hypoxia (FIO2 = 0.12) at rest and during incremental work-rate exercise. Ventilation (V) as well as mean inspiratory flow (VT/TI) increased with exercise intensity and were augmented in the hypoxic environment, whereas the ratio between inspiratory (TI) and total (Ttot) breath durations increased with exercise intensity but was unaffected by hypoxia. The relationship of tidal volume (VT) and inspiratory time duration (TI) showed linear, coinciding ranges for the normoxic and hypoxic conditions up to VT/TI values of about 2.5 1.s-1. At higher VT/TI values TI continued to decrease, whereas VT tended to level off, an effect which was more evident in the hypoxic condition. The results suggest that the hypoxic augmentation of exercise hyperpnea is primarily brought about by an enhancement of central inspiratory drive, the timing component being largely unaffected by the hypoxic environment, and that at low to moderate levels of exercise hyperpnea inspiratory off-switch mechanisms are essentially unaffected by moderate hypoxia.     

A review of the control of breathing during exercise

During the past 100 years many experimental investigations have been carried out in an attempt to determine the control mechanisms responsible for generating the respiratory responses observed during incremental and constant-load exercise tests. As a result of these investigations a number of different and contradictory control mechanisms have been proposed to be the sole mediators of exercise hyperpnea. However, it is now becoming evident that none of the proposed mechanisms are solely responsible for eliciting the exercise respiratory response. The present-day challenge appears to be one of synthesizing the proposed mechanisms, in order to determine the role that each mechanism has in controlling ventilation during exercise. This review, which has been divided into three primary sections, has been designed to meet this challenge. The aim of the first section is to describe the changes in respiration that occur during constant-load and incremental exercise. The second section briefly introduces the reader to traditional and contemporary control mechanisms that might be responsible for eliciting at least a portion of the exercise ventilatory response during these types of exercise. The third section describes how the traditional and contemporary control mechanisms may interact in a complex fashion to produce the changes in breathing associated with constant-load exercise, and incorporates recent experimental evidence from our laboratory.     

Individuality of breathing patterns during hypoxia and exercise.

Breathing was recorded via a pulsed ultrasonic flowmeter in 11 healthy subjects, at rest and during steady-state exercise (at 50% of their maximal O2 consumption) at both sea level (200 m) and simulated altitude (4,500 m in a hypobaric chamber). The pattern of breathing was quantified breath by breath in terms of classical respiratory variables (tidal volume and inspiratory and expiratory times), and the shape of the entire airflow profile was quantified by harmonic analysis. Statistical tests were used to compare the within-individual with the between-individual variations. In comparing the sea level vs. altitude rest (16% increase in ventilation) and sea level vs. altitude exercise (40% increase in ventilation) airflow profiles, we found a significantly greater resemblance within the individual than between individuals. Comparisons of sea level rest and exercise (295% increase in ventilation) and altitude rest and exercise (375% increase in ventilation) revealed no similarity within individuals. Despite airflow profile changes between rest and exercise, it is still possible to attest to a diversity of flow profile between individuals during exercise. Hypoxia at rest or during exercise does not alter the phenomenon of the individuality of breathing patterns.     

Diaphragmatic perfusion heterogeneity during exercise with inspiratory resistive breathing

Regional distribution of diaphragmatic blood flow (Q; 15-microns-diam radionuclide-labeled microspheres) was studied in normal (n = 7) and laryngeal hemiplegic (LH; n = 7) ponies to determine whether the added stress of inspiratory resistive breathing during maximal exercise may cause 1) redistribution of diaphragmatic Q and 2) crural diaphragmatic Q to exceed that in maximally exercising normal ponies. LH-induced augmentation of already high exertional work of breathing resulted in diminished locomotor exercise capacity so that maximal exercise in LH ponies occurred at 25 km/h compared with 32 km/h for normal ponies. The costal and crural regions received similar Q in both groups at rest. However, exercise-induced increments in perfusion were significantly greater in the costal region of the diaphragm. At 25 km/h, costal diaphragmatic perfusion was 154 and 143% of the crural diaphragmatic Q in normal and LH ponies. At 32 km/h, Q in costal diaphragm of normal ponies was 136% of that in the crural region. Costal and crural diaphragmatic Q in LH ponies exercised at 25 km/h exceeded that for normal ponies but was similar to the latter during exercise at 32 km/h. Perfusion pressure for the three conditions was also similar. It is concluded that diaphragmatic perfusion heterogeneity in exercising ponies was preserved during the added stress of inspiratory resistive breathing. It was also demonstrated that vascular resistance in the crural and costal regions of the diaphragm in maximally exercised LH ponies remained similar to that in maximally exercising normal ponies.     

Effects of reduced frequency breathing on arterial hypoxemia during exercise

It is uncertain that exercise with reduced frequency breathing (RFB) results in arterial hypoxemia. This study was designed to investigate whether RFB during exercise creates a true hypoxic condition in arterial blood by examining arterial oxygen saturation (SaO2) directly. Six subjects performed ten 30 s periods of exercise on a Monark bicycle ergometer at a work rate of 210 W alternating with 30 s rest intervals. The breath was controlled to use 1 s each for inspiration and expiration, and two trials with different breathing patterns were used; a continuous breathing (CB) trial and an RFB trial consisting of four seconds of breath-holding at functional residual capacity (FRC). Alveolar oxygen pressure during exercise showed a slight but significant (p less than 0.05) reduction with RFB as compared to CB. However, a marked increase in alveolar-arterial pressure difference for oxygen (A-aDO2) (p less than 0.05) with RFB over CB resulted in a marked (p less than 0.05) reduction in arterial oxygen pressure. Consequently, SaO2 fell as low as 88.8% on average. Additional examination of RFB with breath-holding at total lung capacity showed no increases in A-aDO2 in spite of the same amount of hypoventilation as compared with that at FRC. These results indicate that RFB during exercise can result in arterial hypoxemia if RFB is performed with breath-holding at FRC, this mechanism being closely related to the mechanical responses due to lung volume restriction.     

Regulation of muscle pyruvate metabolism during exercise

Pyruvate dehydrogenase and phosphoenolpyruvate carboxykinase are important enzymes in the regulation of muscle pyruvate metabolism and their in vitro measured activities have been studied in muscle from rested and exercised rats. In addition, the muscle concentration of metabolic intermediates associated with pyruvate metabolism has been measured after exercise. Phosphoenolpyruvate concentration was decreased to less than half the value found in rested muscle but pyruvate concentration did not change. This suggests an increase in the in vivo rate of conversion of phosphoenolpyruvate to pyruvate. Concentrations of malate and aspartate increased two- to threefold which suggests that oxaloacetate concentration was also increased. An increase in oxaloacetate availability would increase acetyl CoA metabolism and therefore would increase pyruvate dehydrogenase activity in vivo. The basal activity of pyruvate dehydrogenase measured in vitro increased approximately twofold after 2 hr of exercise and returned to control values 5 min after the cessation of exercise. Total pyruvate dehydrogenase activity (activated to the maximal extent) was not changed by exercise. Muscle PEPCK activity was also increased during exercise suggesting an increased rate of conversion of oxaloacetate to pyruvate to provide net oxidation of oxaloacetate and other citric acid cycle intermediates. Results of this study demonstrate that the rates of formation and metabolism of pyruvate are increased during exercise.     

Regulation of lactic acid production during exercise

Lactic acid accumulates in contracting muscle and blood beginning at approximately 50-70% of the maximal O2 uptake, well before the aerobic capacity is fully utilized. The classical explanation has been that part of the muscle is O2 deficient and therefore lactate production is increased to provide supplementary anaerobically derived energy. Currently, however, the predominant view is that lactate production during submaximal dynamic exercise is not O2 dependent. In the present review, data and arguments in support of and against the hypothesis of O2 dependency have been scrutinized. Data underlying the conclusion that lactate production during exercise is not O2 dependent were found to be 1) questionable, or 2) interpretable in an alternative manner. Experiments in human and animal muscles under various conditions demonstrated that the redox state of the muscle is reduced (i.e., NADH is increased) either before or in parallel with increases in muscle lactate. Based on experimental data and theoretical considerations, it is concluded that lactate production during submaximal exercise is O2 dependent. The amount of energy provided through the anaerobic processes during steady-state submaximal exercise is, however, low, and the role of lactate formation as an energy source is of minor importance. It is proposed that the achievement of increased aerobic energy formation under conditions of limiting O2 availability requires increases of ADP, Pi, and NADH and that the increases in ADP (and therefore AMP via the adenylate kinase equilibrium) and Pi will stimulate glycolysis, and the resulting increase in cytosolic NADH will shift the lactate dehydrogenase equilibrium toward increased lactate production.     

Regulation of end-expiratory lung volume during exercise

We determined the effects of exercise on active expiration and end-expiratory lung volume (EELV) during steady-state exercise in 13 healthy subjects. We also addressed the questions of what affects active expiration during exercise. Exercise effects on EELV were determined by a He-dilution technique and verified by changes in end-expiratory esophageal pressure. We also used abdominal pressure-volume loops to determine active expiration. EELV was reduced with increasing exercise intensity. EELV was reduced significantly during even mild steady-state exercise and during heavy exercise decreased an average of 0.71 +/- 0.3 liter. Dynamic lung compliance was reduced 30-50%; EELV remained greater than closing volume. Changing the resistance to airflow (via SF6-O2 or He-O2 breathing) during steady-state exercise changed the peak gastric and esophageal pressure generation during expiration but did not alter EELV; breathing through the mouthpiece produced similar effects during exercise. EELV was significantly reduced in the supine position. With supine exercise active expiration was not elicited, and EELV remained the same as in supine rest. With CO2-driven hyperpnea (7-70 l/min), EELV remained unchanged from resting levels, whereas during exercise, at similar minute ventilation (VE) values EELV was consistently decreased. At the same VE, treadmill running caused an increase in tonic gastric pressure and greater reductions in EELV than either walking or cycling. We conclude that both the exercise stimulus and the resultant hyperpnea stimulate active expiration and a reduced FRC. This new EELV is preserved in the face of moderate changes in mechanical time constants of the lung. This reduced EELV during exercise aids inspiration by optimizing diaphragmatic length and permitting elastic recoil of the chest wall.     

Respiratory mechanics and breathing pattern during and following maximal exercise

We looked for evidence of changes in lung elastic recoil and of inspiratory muscle fatigue at maximal exercise in seven normal subjects. Esophageal pressure, flow, and volume were measured during spontaneous breathing at increasing levels of cycle exercise to maximum. Total lung capacity (TLC) was determined at rest and immediately before exercise termination using a N2-washout technique. Maximal inspiratory pressure and inspiratory capacity were measured at 1-min intervals. The time course of instantaneous dynamic pressure of respiratory muscles (Pmus) was calculated for the spontaneous breaths immediately preceding exercise termination. TLC volume and lung elastic recoil at TLC were the same at the end of exercise as at rest. Maximum static inspiratory pressures at exercise termination were not reduced. However, mean Pmus of spontaneous breaths at end exercise exceeded 15% of maximum inspiratory pressure in five of the subjects. We conclude that lung elastic recoil is unchanged even at maximal exercise and that, while inspiratory muscles operate within a potentially fatiguing range, the high levels of ventilation observed during maximal exercise are not maintained for a sufficient time to result in mechanical fatigue.     

Rib cage mechanics during quiet breathing and exercise in humans

Kenyon, C. M., S. J. Cala, S. Yan, A. Aliverti, G. Scano, R. Duranti, A. Pedotti, and Peter T. Macklem. Rib cage mechanics during quiet breathing and exercise in humans. J. Appl. Physiol. 83(4): 1242-1255, 1997.Duringexercise, large pleural, abdominal, and transdiaphragmatic pressureswings might produce substantial rib cage (RC) distortions. We used athree-compartment chest wall model (J. Appl.Physiol. 72: 1338-1347, 1992) to measuredistortions of lung- and diaphragm-apposed RC compartments (RCp andRCa) along with pleural and abdominal pressures in five normal men. RCpand RCa volumes were calculated from three-dimensional locations of 86 markers on the chest wall, and the undistorted (relaxation) RCconfiguration was measured. Compliances of RCp and RCa measured duringphrenic stimulation against a closed airway were 20 and 0%,respectively, of their values during relaxation. There was marked RCdistortion. Thus nonuniform distribution of pressures distorts the RCand markedly stiffens it. However, during steady-state ergometerexercise at 0, 30, 50, and 70% of maximum workload, RC distortionswere small because of a coordinated action of respiratory muscles, sothat net pressures acting on RCp and RCa were nearly the samethroughout the respiratory cycle. This maximizes RC compliance andminimizes the work of RC displacement. During quiet breathing, plots ofRCa volume vs. abdominal pressure were to the right of the relaxationcurve, indicating an expiratory action on RCa. We attribute this topassive stretching of abdominal muscles, which more thancounterbalances the insertional component of transdiaphragmatic pressure.