Extension of the Functional Range of Respiratory and Gas Exchange Responses in Repetitive Hypoxia

External respiration and gas exchange were studied in healthy volunteers during a session of intermittent normobaric hypoxia (INH) consisting of three cycles of breathing alternately a hypoxic mixture (10.7% O₂) for 5 min and normal air for 5 min. The ventilatory response increased in the successive cycles of hypoxia and gradually decreased during the normoxic intervals. These changes were accompanied by an increase in carbon dioxide in lung air, which was not eliminated by the increased pulmonary ventilation during the hypoxic intervals. However, the mean oxygen consumption did not change during the INH session because the ventilatory reactivity and breathing depth, as well as the efficiency of oxygen utilization, increased from cycle to cycle.__________Translated from Fiziologiya Cheloveka, Vol. 31, No. 3, 2005, pp. 100–107.Original Russian Text Copyright © 2005 by Krivoshchekov, G. Divert, V. Divert.     

Respiratory sinus arrhythmia is associated with efficiency of pulmonary gas exchange in healthy humans

Respiratory sinus arrhythmia (RSA) may be associated with improved efficiency of pulmonary gas exchange by matching ventilation to perfusion within each respiratory cycle. Respiration rate, tidal volume, minute ventilation (.VE), exhaled carbon dioxide (.VCO(2)), oxygen consumption (.VO(2)), and heart rate were measured in 10 healthy human volunteers during paced breathing to test the hypothesis that RSA contributes to pulmonary gas exchange efficiency. Cross-spectral analysis of heart rate and respiration was computed to calculate RSA and the coherence and phase between these variables. Pulmonary gas exchange efficiency was measured as the average ventilatory equivalent of CO(2) (.VE/.VCO(2)) and O(2) (.VE/.VO(2)). Across subjects and paced breathing periods, RSA was significantly associated with CO(2) (partial r = -0.53, P = 0.002) and O(2) (partial r = -0.49, P = 0.005) exchange efficiency after controlling for the effects of age, respiration rate, tidal volume, and average heart rate. Phase between heart rate and respiration was significantly associated with CO(2) exchange efficiency (partial r = 0.40, P = 0.03). These results are consistent with previous studies and further support the theory that RSA may improve the efficiency of pulmonary gas exchange.     

Effect of Short-Term Intermittent Normobaric Hypoxia on the Regulation of External Respiration in Humans

Baseline external respiration and gas exchange values, as well as ventilatory thresholds and sensitivity to the O₂ and CO₂ stimuli in hypoxic and hypercapnic tests, were measured 1 h before and after a session of intermittent normobaric hypoxia (INH) (six repetitions with a 5-min inhalation of a gas mixture (10% O₂) alternating with a 3-min inhalation of atmospheric air). After an INH session, the background CO₂ level in the lungs increased by 10%. In the hypercapnic test, the actuation threshold of the ventilatory response did not change, whereas ventilatory sensitivity increased. The maximal pulmonary ventilation and the corresponding critical CO₂ level in the lungs also increased at the end of the test. In the hypoxic test, the ventilatory response occurred at a decreased level of blood oxygenation after an INH session, the pulmonary ventilation level being decreased and the CO₂ content in the lungs being increased at the end of the test. The data obtained evidence the maintenance of changed gas homeostasis for 1 h after an INH session. In this process, control of respiration was effected, with the hypoxic drive being weakened and the peripheral chemoreceptor sensitivity being decreased. The hypercapnic drive also increased, which may be determined by readjustment in the central mechanisms of respiratory regulation.     

Compensatory and adaptive rearrangement in the human respiratory system under acute hypoxic conditions

Relationships between the parameters of external respiration (minute volume and respiration rate) and those of internal, tissue respiration (oxygen consumption, arteriovenous oxygen difference and efficiency of oxygen uptake) were studied during a period of acute hypoxia and upon its completion. The subjects were exposed to hypoxia for 25 min using oxygen-nitrogen hypoxic gas mixtures (HGMs) differing in oxygen content (8 and 12%, HGM-8 and HGM-12, respectively). From the third to the fifth minutes of exposure to HGM-8, the respiration minute volume (RMV) was found to increase by 51 ± 33% as compared to the background value; however, the body’s oxygen consumption (OC) was 35 ± 22% reduced. Afterwards, OC grew to reach, from the 20th to the 25th min of hypoxia, 108 ± 21% of the background value and 181% of the value determined from the third to the fifth minutes of hypoxia. OC growth was accompanied by an insignificant RMV increase (by 12%) as compared to the level determined from the third to the fifth minutes of hypoxia, whereas the efficiency of oxygen uptake from the arterial blood increased by 75% for the same period. RMV growth from the third to the fifth minutes of hypoxia occurred as expense result of a higher breathing depth; at the same time, the respiration rate decreased as compared to the background value. By the period from the 20th to the 25th min of exposure to HGM-8, the respiration rate increased by 21% as compared to the period from the third to the fifth minutes of hypoxia. The efficiency of oxygen uptake from the arterial blood remained higher than the background value for at least 5 min after completion of the exposure to HGM-8. During the same period, the ventilation equivalent, an indicator of the efficiency of external respiration, i.e., of oxygen supply to the body, was significantly lower than the background value. During the exposure to HGM-12, RMV increased to a lesser extent than on exposure to HGM-8, however, the efficiency of oxygen uptake was higher during exposure to HGM-12; therefore, OC was also higher in the latter case. Therefore, the assumption that, during hypoxia, intensified external respiration (ventilatory response) itself compensates oxygen deficiency in inhaled air is revised. Ventilatory response is only a portion of the entire functional system of respiration (both external and tissue respiration). The role of ventilatory response is important for conditioning the tissue respiration rearrangement to eliminate deficiency of oxygen consumption during hypoxia. The retained higher oxygen uptake from the arterial blood during the period after completion of hypoxic treatment testifies to the adaptive implication of changes in tissue respiration; the same is confirmed by a reduced ventilation equivalent after hypoxia, which is indicative of the growing efficiency of external respiration, i.e., of an improved oxygen supply to the body.     

Intermittent Normobaric Hypoxia as a Model of Incomplete Adaptation

The Neirokartograf software was used to calculate the correlations between EEG, external respiration, and gas exchange parameters recorded in the initial state, after 10 or 20 sessions of intermittent normobaric hypoxia (INH), and after its cessation. It was demonstrated that cerebral structures were increasingly involved in gas exchange control in ascending order during the course of INH sessions. The artificial short-term extreme exposure followed by a return to usual conditions resulted in incomplete adaptation. Even 20 days after the cessation of INH sessions, neurodynamics did not return to the initial state.     

Functional reaction of the human body to different ways of respiration regulation

Reactions of the body to different ways of regulation of respiration, i.e., through the elastic resistance to respiratory movements and external dead space volume, as well as voluntary hyper- and hypoventilation, were studied. An increased elastic resistance to respiratory movements was established to create conditions for intense loading of respiratory musculature and to determine an increased in oxygen consumption. An increase in the external dead space produces a marked complex reaction of the body to the hypoxichypercapnic content of the inhaled gas mixture, causing hyperventilation and heightened work of the respiratory musculature and stimulating metabolism. Voluntary hyperventilation during muscular effort leads to a state of relative hypocapnia, gross loss of efficiency, and economic external respiration and gas exchange. Voluntary hypoventilation in the course of muscular effort brings about marked shifts in gas homeostasis towards alveolar hypoxia and hypercapnia. A concurrent increase in the efficiency and economy of external respiration and gas exchange is observed.     

Ozone and high ventilation effects on pulmonary function and endurance performance

Ozone (O3) toxicity is potentiated by exercise-induced expired minute ventilation (VE) for a given exposure, which may also impair endurance performance. Ten healthy, well-trained long-distance runners were exposed on six occasions for 1 h to O3 concentrations of 0, 0.20, or 0.35 parts per million (ppm), during exercise simulating either training or competition, with mean VE = 77.5 1 X min -1. Standard pulmonary function tests, subjective symptoms, and periodic observations of exercise ventilatory response and respiratory metabolism were obtained. Statistical analyses revealed no significant exercise mode effect for pulmonary function, but a significant O3 effect for forced vital capacity and expiratory volume at 1 s was observed. Altered exercise ventilatory pattern response was noted, but there was no significant O3 effect on exercise oxygen uptake, heart rate, VE, or alveolar ventilation. Subjective symptoms increased with O3 concentration. Statistically significant pulmonary function impairment observed at 0.20 ppm O3 suggests that endurance athletes may be more susceptible to the effects of a given O3 concentration than normal young adult males as a result of sustained high mean VE incurred during training and competition. Three subjects were unable to complete both the training and competitive simulations at 0.35 ppm O3. Performance decrements appeared to be the result of physiologically induced respiratory discomfort rather than decrements in pulmonary gas exchange and/or oxygen transport and delivery.     

Standardized estimation of external respiration function

External respiration in healthy males has, in addition to eupnea, six functionally active variants with one or several indices deviating from the normal values. Hyperpnea and hypopnea are determined by deviations in general oxygen consumption accompanied by adequate changes in pulmonary ventilation and gas exchange. Inhibition of gas exchange in the respiratory parts of the lungs is a typical primary event of hyperventilation, a fact indicated by a decrease in the coefficient of oxygen consumption and a compensatory increase in the minute respiratory volume during hyperventilation. Tension of the respiratory system is especially pronounced during enhanced oxygen consumption (O₂C). Highly effective bradypnea is characterized by infrequent and deep breathing. No tension of the respiratory system is observed even for increased O₂C. This state may be considered a genotypic and phenotypic variant of normal respiration. The data obtained may be used to automate the assessment of gas exchange in the respiratory parts of the lungs.     

Response of subjects trained to hold their breath to intermittent normobaric hypoxia

The change in the external respiration parameters was studied in individuals engaging in sports (swimming) combined with training in voluntary cyclic breath holding during a session of intermittent normobaric hypoxia (three cycles of 5 min breathing a gas mixture containing 10.7% O₂ alternating with 5 min breathing ordinary air). It was shown that they differed from the control group in sharp variations in the oxygen consumption rate, which were accompanied by equally marked changes in the effectiveness of oxygen binding in the lungs with a slightly increased stable level of pulmonary ventilation and a bradypneic type of breathing. An increase in the alveolar concentration of carbonic acid and a dramatic increase in the effectiveness of its elimination are significant features of the adaptive process in the mechanism of regulation of external respiration in this training.     

Respiratory responses of the striped mullet,Mugil cephalus (L.) to hypoxic conditions*

Ventilation volume, ventilatory frequency, ventilatory stroke volume, percentage utilization of oxygen and respiratory metabolism were measured on unanaesthetized striped mullet, Mugil cephalus L., under ambient and hypoxic conditions with a modified van Dam respiration chamber. Hypoxia caused a statistically significant increase in ventilation volume, ventilatory frequency, and ventilatory stroke volume and a significant decrease in percentage utilization of oxygen. The routine rate of respiratory metabolism was not significantly altered by hypoxia. These responses probably represent ventilatory adjustments which serve to maintain a constant oxygen supply to the gills under conditions of oxygen depletion.     

Comparative analysis of gas exchange and cardiorespiratory system responses of swimmers and skiers to increasing normobaric hypoxia and physical load

Qualification-comparable groups of young men engaged in cyclic kinds of sports were tested using a stepwise increasing load on a bicycle ergometer and 25-min exponentially increasing normobaric hypoxia to a final oxygen concentration of 10%. Skiers, who had the greatest values of maximal oxygen consumption during muscular work, showed relaxed cardiorespiratory reactions and a greater decrease in hemoglobin saturation with oxygen in hypoxia. Swimmers, whose ventilatory function in the course of trainings was restricted, developed preadaptation to hypoxia, with changes in external respiration and gas exchange functions, which allowed better saturation of blood with oxygen in lungs during hypoxia. The joint assessment of the aerobic capacity during physical work and physiological responses to hypoxia showed a direct correlation between the individual maximal oxygen consumption and the rate of decrease in the blood hemoglobin saturation in increasing hypoxia, which may be promising for assessing the functional state of athletes and its correction during training.     

Rates of breathing values and kinetics of respiration response in critical patterns of muscular activity in middle and long distance running

In elite runners, the ventilation influx, ventilation debt, and ventilation demand of the exercises were calculated on the basis of the pulmonary respiration dynamics during the maximum workout and recovery. The breathing values proved to closely reproduce the changes in the main parameters of oxygen demand at high intensity and duration of the exercise and can be used for quantification and standardization of exercise loads in sports. Three important factors of the aerobic exchange in the body were found to ensure the high level of the sports achievements in running: (1) general increase in the level of pulmonary ventilation (VE), oxygen demand (VO₂), and release of carbon dioxide (CO₂); (2) intensity of oxygen supply from lungs to the working muscles; (3) the rate of oxygenation (StO₂) and total rate of blood circulation.     

Precision of ventilatory and gas exchange alterations as a predictor of the anaerobic threshold

Anaerobic threshold has been defined as the oxygen uptake (VO2) at which blood lactate (La) begins to rise systematically during graded exercise (Davis et al. 1982). It has become common practice in the literature to estimate the anaerobic threshold by using ventilatory and/or gas exchange alterations. However, confusion exists as to the validity of this practice. The purpose of this study was to examine the precision with which ventilatory and gas exchange techniques for determining anaerobic threshold predicted the anaerobic threshold resolved by La criteria. The anaerobic threshold was chosen using three criteria: (1) systematic increase in blood La (ATLa), (2) systematic increase in ventilatory equivalent for O2 with no change in the ventilatory equivalent for CO2 (ATVE/VO2), and (3) non-linear increase in expired ventilation graphed as a function of VO2 (ATVE). Thirteen trained male subjects performed an incremental cycle ergometer test to exhaustion in which the load was increased by 30 W every 3 minutes. Ventilation, gas exchange measures, and blood samples for La analysis were obtained every 3rd min throughout the test. In five of the thirteen subjects tested the anaerobic threshold determined by ventilatory and gas exchange alterations did not occur at the same VO2 as the ATLa. The highest correlation between a gas exchange anaerobic threshold and ATLa was found for ATVE/VO2 and was r = 0.63 (P less than 0.05). These data provide evidence that the ATLa and ATVE do not always occur simultaneously and suggest limitations in using ventilatory or gas exchange measures to estimate the ATLa.     

Hypoxic pulmonary vasoconstriction as a regulator of alveolar-capillary oxygen flux: A computational model of ventilation-perfusion matching

The relationship between regional variabilities in airflow (ventilation) and blood flow (perfusion) is a critical determinant of gas exchange efficiency in the lungs. Hypoxic pulmonary vasoconstriction is understood to be the primary active regulator of ventilation-perfusion matching, where upstream arterioles constrict to direct blood flow away from areas that have low oxygen supply. However, it is not understood how the integrated action of hypoxic pulmonary vasoconstriction affects oxygen transport at the system level. In this study we develop, and make functional predictions with a multi-scale multi-physics model of ventilation-perfusion matching governed by the mechanism of hypoxic pulmonary vasoconstriction. Our model consists of (a) morphometrically realistic 2D pulmonary vascular networks to the level of large arterioles and venules; (b) a tileable lumped-parameter model of vascular fluid and wall mechanics that accounts for the influence of alveolar pressure; (c) oxygen transport accounting for oxygen bound to hemoglobin and dissolved in plasma; and (d) a novel empirical model of hypoxic pulmonary vasoconstriction. Our model simulations predict that under the artificial test condition of a uniform ventilation distribution (1) hypoxic pulmonary vasoconstriction matches perfusion to ventilation; (2) hypoxic pulmonary vasoconstriction homogenizes regional alveolar-capillary oxygen flux; and (3) hypoxic pulmonary vasoconstriction increases whole-lobe oxygen uptake by improving ventilation-perfusion matching.     

Effect of prolonged running on physiological responses to subsequent exercise

The purpose of this study was to compare metabolic and cardiopulmonary responses for submaximal and maximal exercise performed several days preceding (pre-test) and 45 min after (post-test) 21 miles of high intensity (70% VO2 max) treadmill running. Seven aerobically trained subjects' oxygen uptake, oxygen pulse, respiratory exchange ratio, heart rate, pulmonary ventilation, ventilatory equivalent of oxygen, and blood lactate concentration were determined for exercise during the pre- and post-test sessions. No differences were found for submaximal oxygen uptake, oxygen pulse, pulmonary ventilation and ventilatory equivalent of oxygen between the pre- and post-test values. Generally, submaximal heart rate responses were higher, and respiratory exchange ratio values were lower during the post-test. Reductions of maximal work time (12%), maximal oxygen uptake (6%) and maximal blood lactate concentration (47%) were found during the post-test. Thermal stress and glycogen depletion are possible mechanisms which may be responsible for these observed differences.     

肺动脉高压及其合并心脏内右向左分流患者的心肺运动试验特征性变化的临床研究*

目的: 明确肺动脉高压及合并心脏内右向左分流（R-L）患者的心肺运动试验（CPET）气体交换变化。方法: 本文通过回顾性分析阜外医院从2016-10至2017-08签署知情同意书后完成CPET的73例肺动脉高压病人CPET数据,采取双盲方式抽取四位医生作为判读者分别独立识别R-L后,结果分为四组：①分流阳性组（n=20）、②分流可疑组（n=9）、③无分流组（n=37）、④分流延迟开放组（n=6）。选择同期完成CPET正常人14例作为对照。结果: 分流阳性组在运动开始时分钟通气量、二氧化碳排出通气效率、氧气通气效率和呼气末氧分压相对于静息期的改变值骤升,分别为（7.36±2.72） L/min、（1.84±3.59）、（5.02±4.34）、（3.75±2.64） mmHg）,明显高于对照组的（（4.26±2.59） L/min、（2.22±2.08）、（-1.46±4.68）、（-3.96±2.82） mmHg）;而呼气末二氧化碳分压相对于静息期的改变值骤降（-1.63±1.66） mmHg,明显低于对照组的（2.22±2.08） mmHg（P均<0.01）。分流延迟开放组在运动后期呼吸商（RER）、二氧化碳排出通气效率、氧气通气效率和呼气末氧分压相对于静息期的改变值骤升,分别为（0.40±0.08）、（11.07±5.60）、（30.55±7.89）、（13.72±2.21） mmHg,明显高于对照组的（0.38±0.12）、（5.67±4.6）、（4.54±3.83）、（5.51±4.24） mmHg;而呼气末二氧化碳分压相对于静息期的改变值骤降（-6.82±1.96） mmHg,明显区别于对照组的（5.67±4.6） mmHg,在恢复期分流延迟开放组二氧化碳排出通气效率、氧气通气效率相对于峰值功率时的改变值（分别为-8.38±3.24、-13.14±6.47）,明显低于对照组（6.22±2.87、16.56±4.2）（P均<0.01）。结论: 肺动脉高压患者较正常人CPET的整体功能和通气效率指标降低;肺动脉高压合并右向左分流患者不仅在静息通气效率受限更剧;且特征性地运动初始时出现PETO₂明显上升、PETCO₂明显下降,RER跳升到1.0左右,VE/VCO₂ 不降反升与VO₂/VE不升反降, 常有SpO₂显著下降,还有VE更大幅度上升;延迟开放型上述特征性变化发生在运动接近峰值的1~3 min而非运动初始,且运动停止后迅速反向变回以示重新关闭。     

An increased carbon dioxide production in transient hypoxia in healthy subjects at rest

Indices of pulmonary gas exchange and heart rate (HR) have been measured in 24 healthy subjects not adapted to hypoxia after hypoxic aerial mixture (HAM) (17, 15, 13 vol % of oxygen) respiration for 15 min. Using group data analysis, it has been shown that hypoxia under the conditions of inhalation of 17 and 15 vol % of O₂ caused no significant changes. Hypoxia under the conditions of 13 vol % of O₂ inhalation is a threshold one, when ventilation (SpO₂) drops below 85%. A significant increase in the lung ventilation (Ve) (10–14%, p < 0.05) and HR (11–15%, p < 0.05) have been observed in this case. Hyperpnea was accompanied by an increase in the oxygen uptake rate by 10% and carbon dioxide release rate (10–18%, p < 0.05). On the contrary, individual data analysis showed changes in the pulmonary gas exchange indices in 90% of subjects in the case of inhalation of 17 vol % of O₂ HAM. Four response types have been found: ventilation (increase in lung ventilation), hypoxic hypometabolism (decrease in oxygen consumption rate), and mobilization response (increase in oxygen utilization in the lungs), and anaerobic response, which is expressed in an increase in the carbon dioxide release rate along with an increase in the respiratory quotient. All these responses are of an individual type, but the ventilation response is developed in response to hypoxia caused by inhalation of 13 vol % of O₂ HAM and a decrease in SpO₂ below 85% in more than 60% of cases.     

External respiration response of trained skiers to intermittent normobaric hypoxia

As part of a study on the resistance of subjects adapted to aerobic physical activity to hypoxia, the ventilatory response of trained skiers whose regular physical training is associated with hyperventilation to intermittent normobaric hypoxia has been analyzed. A test session consisted of three cycles of breathing alternately a hypoxic gas mixture (10 vol % O₂) for 5 min and normal air for 5 min. The skiers have a lower oxygen consumption rate as compared with untrained subjects, i.e., a reduced resistance to hypoxia. Therefore, the efficiency of respiration during hypoxia is lower in atheltes, which is caused by a rapid decrease in blood oxygenation, whereas during breathing normal atmospheric air, the efficiency of respiration is lower in untrained subjects.     

Supramaximal exercise after training-induced hypervolemia. I. Gas exchange and acid-base balance

The effect of an exercise-induced reduction in blood O2-carrying capacity on ventilatory gas exchange and acid-base balance during supramaximal exercise was studied in six males [peak O2 consumption (VO2peak), 3.98 +/- 0.49 l/min]. Three consecutive days of supramaximal exercise resulted in a preexercise reduction of hemoglobin concentration from 15.8 to 14.0 g/dl (P less than 0.05). During exercise (120% VO2peak) performed intermittently (1 min work to 4 min rest); a small but significant (P less than 0.05) increase was found for both O2 consumption (VO2) (l X min) and heart rate (beats/min) on day 2 of the training. On day 3, VO2 (l/min) was reduced 3.2% (P less than 0.05) over day 1 values. No changes were found in CO2 output and minute ventilation during exercise between training days. Similarly, short-term training failed to significantly alter the changes in arterialized blood PCO2, pH, and [HCO-3] observed during exercise. It is concluded that hypervolemia-induced reductions in O2-carrying capacity in the order of 10-11% cause minimal impairment to gas exchange and acid-base balance during supramaximal non-steady-state exercise.     

Early adaptations in gas exchange, cardiac function and haematology to prolonged exercise training in man

In order to determine the effect of short-term training on central adaptations, gas exchange and cardiac function were measured during a prolonged submaximal exercise challenge prior to and following 10-12 consecutive days of exercise. In addition, vascular volumes and selected haematological properties were also examined. The subjects, healthy males between the ages of 19 and 30 years of age, cycled for 2 h per day at approximately 59% of pre-training peak oxygen consumption (VO2) i.e., maximal oxygen consumption (VO2max). Following the training, VO2max (l.min-1) increased (P less than 0.05) by 4.3% (3.94, 0.11 vs 4.11, 0.11; mean, SE) whereas maximal exercise ventilation (VE,max) and maximal heart rate (fc,max) were unchanged. During submaximal exercise, VO2 was unaltered by the training whereas carbon dioxide production (VE) and respiratory exchange ratio were all reduced (P less than 0.05). The altered activity pattern failed to elicit adaptations in either submaximal exercise cardiac output or arteriovenous O2 difference. fc was reduced (P less than 0.05). Plasma volume (PV) as measured by 125I human serum albumin increased by 365 ml or 11.8%, while red cell volume (RCV) as measured by 51chromium-labelled red blood cells (RBC) was unaltered. The increase in PV was accompanied by reductions (P less than 0.05) in haematocrit, haemoglobin concentration (g.100 ml-1), and RBCs (10(6) mm-3). Collectively these changes suggest only minimal adaptations in maximal oxygen transport during the early period of prolonged exercise training. However, as evidenced by the changes during submaximal exercise, both the ventilatory and the cardiodynamic response were altered.(ABSTRACT TRUNCATED AT 250 WORDS)