Self-controlled artificial respiration

We compared respiratory parameters during natural and self-controlled mechanical breathing to investigate mechanisms of respiratory control in alert humans. The self-control of mechanical breathing is realised manually: duration and velocity of air flow are controlled by left and right hands, resp. In this case, the respiratory afferent information is used to control activity of hand muscles but not of breathing muscles. The findings show that lung ventilation during self-controlled mechanical breathing increases by 7.5 l/min. at resting, by 6.3 l/min. during an exercise, as compared with the natural breathing. The increase in the lung ventilation occurs on account of an increase in the tidal volume but the frequency of the self-controlled mechanical breathing tends to be lesser at resting and was statistically significantly lower in exercise that at natural breathing. The exercise increases the lung ventilation by 13.0 l/min. at natural breathing and by 11.8 l/min. during self-controlled mechanical breathing. The findings suggest that the increased lung ventilation during self-controlled mechanical breathing is connected with creation of a new movement skill, and the modified pattern of self-controlled mechanical breathing is caused by a process of cortical transformation of respiratory afferents signals to efferent signals towards the hand muscles.     

The coupled evolution of breathing and locomotion as a game of leapfrog

Because the increase in metabolic rate related to locomotor activity places demands on the cardiorespiratory apparatus, it is not surprising that the evolution of breathing and of locomotion are coupled. As the respiratory faculty becomes more refined, increasingly aerobic life strategies can be explored, and this activity is in turn expedited by a higher-performance respiratory apparatus. This apparent leapfrogging of respiratory and locomotor faculties begins in noncraniate chordates and continues in water-breathing and air-breathing vertebrates. Because both locomotor and cardiorespiratory activities are coordinated in the brain, neurological as well as biochemical coupling is evident. In spite of very different breathing mechanisms in various vertebrate groups, the basic respiratory control mechanisms appear to have been conserved, and respiratory-locomotor coupling is evident in all classes of vertebrates. Hypaxial body wall muscles that were strictly locomotor in fish have respiratory function in amniotes, but some locomotor function remains in all groups.     

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.     

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment (RMCA) in Individuals with Chronic Spinal Cord Injury

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination is disrupted by spinal cord injury (SCI), control of respiratory muscles innervated below the injury level is compromised^1,2 leading to respiratory muscle dysfunction and pulmonary complications. These conditions are among the leading causes of death in patients with SCI³. Standard pulmonary function tests that assess respiratory motor function include spirometrical and maximum airway pressure outcomes: Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV₁), Maximal Inspiratory Pressure (PI_max) and Maximal Expiratory Pressure (PE_max)^4,5. These values provide indirect measurements of respiratory muscle performance⁶. In clinical practice and research, a surface electromyography (sEMG) recorded from respiratory muscles can be used to assess respiratory motor function and help to diagnose neuromuscular pathology. However, variability in the sEMG amplitude inhibits efforts to develop objective and direct measures of respiratory motor function⁶. Based on a multi-muscle sEMG approach to characterize motor control of limb muscles⁷, known as the voluntary response index (VRI)⁸, we developed an analytical tool to characterize respiratory motor control directly from sEMG data recorded from multiple respiratory muscles during the voluntary respiratory tasks. We have termed this the Respiratory Motor Control Assessment (RMCA)⁹. This vector analysis method quantifies the amount and distribution of activity across muscles and presents it in the form of an index that relates the degree to which sEMG output within a test-subject resembles that from a group of healthy (non-injured) controls. The resulting index value has been shown to have high face validity, sensitivity and specificity^9-11. We showed previously⁹ that the RMCA outcomes significantly correlate with levels of SCI and pulmonary function measures. We are presenting here the method to quantitatively compare post-spinal cord injury respiratory multi-muscle activation patterns to those of healthy individuals.     

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.     

Respiratory responses to microinjections of gastrin-releasing peptide into the solitary tract nucleus

In acute experiments on urethane-anesthetized rats, the respiratory effects ofmicroinjections of 10(-5), 10(-8) and 10(-10) M gastrin-releasing peptide (GRP) into the solitary tract nucleus were investigated. It was found that microinjections of the neuropeptide induced an increase in tidal volume, amplitude of diaphragm and external intercostal muscles firing activity and in expiratory duration. The most obvious respiratory responses observed when 10(-8) M GRP was used, while 10(-10) M GRP appeared to be sub-threshold and didn't alter the breathing pattern and activity of inspiratory muscles. In some experiments, where the blood pressure and the heart rate was monitored alone with breathing pattern, these parameters did not change after GRP microinjections into the solitary tract nucleus. The obtained data together with particularities of the distribution of GRP receptors in the brainstem suggest the possibility of GRP involvement into the respiratory control mechanisms at the level of solitary tract nucleus.     

Does the respiratory system limit the aerobic working capacity of humans?

The question concerning respiratory function reserves among the factors determining the maximal power of muscular work is considered. Even in strenuous physical exercise, pulmonary ventilation does not exceed a rather constant level for every individual. Studies conducted using the programmed isocapnic hyperpnea method developed by the authors demonstrated that this level precisely reflects the functional respiratory reserve that is one of the factors limiting maximal work performance intensity. Under normal conditions, the functional respiratory reserve is 20 to 40% less than the so-called maximal breathing capacity (MBC) determined in a test, which requires voluntarily forcing respiratory efforts and exorbitant energy expenditure for the respiratory muscles performance. Therefore, the MBC should be regarded only as a parameter of ventilatory forced capacity used in extreme situations such as competitive athletic loading or in more resistive breathing when decreased respiratory system reserves become a leading factor rigidly limiting aerobic working capacity. A scheme is given that illustrates the ambiguous role of the respiratory system in this aspect.     

Strategies of adaptation of small arteries in diaphragm and gastrocnemius muscle to aerobic exercise training

Aerobic exercise training is associated with adaptive changes in skeletal muscles and their vascular bed; such changes in individual muscles may vary depending on their characteristics and recruitment. This study was aimed at comparing the effects of eight-week treadmill training on the locomotor and respiratory muscles in rats. The training course increased the aerobic performance in rats, which was evidenced by an increase in maximum O₂ consumption and a decrease in the blood lactate concentration in ramp test. The succinate dehydrogenase activity was increased in the red portion of the gastrocnemius muscle, but not in the diaphragm of trained rats. Arterial segments were isolated from feed arteries and studied by wire myography. The relaxation in response to acetylcholine in gastrocnemius arteries in trained animals was higher as compared with controls (due to higher NO production), while contractile responses to noradrenaline (in the presence of propranolol) were not changed. On the contrary, the endothelial function of diaphragm arteries was not affected by training, but contractile responses to activation of α-adrenoceptors were markedly increased. Thus, aerobic training may increase the blood supply rate to both locomotor and respiratory muscles, but the underlying regulatory mechanisms are different. The results obtained allow us to reveal the physiological mechanisms that determine the physical performance of the body under conditions of compromised functioning of the respiratory system.     

Cervical spinal cord injury alters the pattern of breathing in anesthetized rats.

The mechanisms by which chronic cervical spinal cord injury alters respiratory function and plasticity are not well understood. We speculated that spinal hemisection at C(2) would alter the respiratory pattern controlled by vagal mechanisms. Expired volume (V(E)) and respiratory rate (RR) were measured in anesthetized control and C(2)-hemisected rats at 1 and 2 mo postinjury. C(2) hemisection altered the pattern of breathing at both postinjury time intervals. Injured rats utilized a higher RR and lower V(E) to maintain the same minute ventilation as control rats. After bilateral vagotomy, the pattern of breathing in injured rats was not different from controls. The frequency of augmented breaths was higher in injured rats at 2 mo postinjury before vagotomy; however, the V(E) of augmented breaths was not different between groups. In conclusion, C(2) hemisection alters the pattern of breathing at 1 and 2 mo postinjury via vagal mechanisms.     

The evolution of human speech: The role of enhanced breathing control

Many cognitive and physical features must have undergone change for the evolution of fully modern human language. One neglected aspect is the evolution of increased breathing control. Evidence presented herein shows that modern humans and Neanderthals have an expanded thoracic vertebral canal compared with australopithecines and Homo ergaster, who had canals of the same relative size as extant nonhuman primates. Based on previously published analyses, these results demonstrate that there was an increase in thoracic innervation during human evolution. Possible explanations for this increase include postural control for bipedalism, increased difficulty of parturition, respiration for endurance running, an aquatic phase, and choking avoidance. These can all be ruled out, either because of their evolutionary timing, or because they are insufficiently demanding neurologically. The remaining possible functional cause is increased control of breathing for speech. The main muscles involved in the fine control of human speech breathing are the intercostals and a set of abdominal muscles which are all thoracically innervated. Modifications to quiet breathing are essential for modern human speech, enabling the production of long phrases on single expirations punctuated with quick inspirations at meaningful linguistic breaks. Other linguistically important features affected by variation in subglottal air pressure include emphasis of particular sound units, and control of pitch and intonation. Subtle, complex muscle movements, integrated with cognitive factors, are involved. The vocalizations of nonhuman primates involve markedly less respiratory control. Without sophisticated breath control, early hominids would only have been capable of short, unmodulated utterances, like those of extant nonhuman primates. Fine respiratory control, a necessary component for fully modern language, evolved sometime between 1.6 Mya and 100,000 ya. Am J Phys Anthropol 109:341–363, 1999. © 1999 Wiley-Liss, Inc.     

Coordination of intrinsic and extrinsic tongue muscles during spontaneous breathing in the rat.

The muscular-hydrostat model of tongue function proposes a constant interaction of extrinsic (external bony attachment, insertion into base of tongue) and intrinsic (origin and insertion within the tongue) tongue muscles in all tongue movements (Kier WM and Smith KK. Zool J Linn Soc 83: 207-324, 1985). Yet, research that examines the respiratory-related effects of tongue function in mammals continues to focus almost exclusively on the respiratory control and function of the extrinsic tongue protrusor muscle, the genioglossus muscle. The respiratory control and function of the intrinsic tongue muscles are unknown. Our purpose was to determine whether intrinsic tongue muscles have a respiration-related activity pattern and whether intrinsic tongue muscles are coactivated with extrinsic tongue muscles in response to respiratory-related sensory stimuli. Esophageal pressure and electromyographic (EMG) activity of an extrinsic tongue muscle (hyoglossus), an intrinsic tongue muscle (superior longitudinal), and an external intercostal muscle were studied in anesthetized, tracheotomized, spontaneously breathing rats. Mean inspiratory EMG activity was compared at five levels of inspired CO2. Intrinsic tongue muscles were often quiescent during eupnea but active during hypercapnia, whereas extrinsic tongue muscles were active in both eupnea and hypercapnia. During hypercapnia, the activities of the airway muscles were largely coincident, although the onset of extrinsic muscle activity generally preceded the onset of intrinsic muscle activation. Our findings provide evidence, in an in vivo rodent preparation, of respiratory modulation of motoneurons supplying intrinsic tongue muscles. Distinctions noted between intrinsic and extrinsic activities could be due to differences in motoneuron properties or the central, respiration-related control of each motoneuron population.     

Genioglossus and alae nasi activity in fetal sheep

The functional development of two upper airway dilating muscles, the alae nasi and the genioglossus, has been studied in fetal sheep in utero from 112-140 days gestation. Before electrocortical differentiation phasic activity was present in both muscles for long periods, mostly when breathing movements were present. After 120 days gestation phasic genioglossal and alae nasi activity occurred only during periods of low voltage electrocortical activity. During high voltage episodes there was no phasic activity and tonic activity was not sustained. Although present during periods of breathing movements genioglossus activity was rarely synchronous with the diaphragm. The alae nasi showed both respiratory and non-respiratory related activity. Hypoxia abolished both alae nasi and genioglossus activity but whereas alae nasi rapidly developed an inspiratory rhythm during 5% CO2 administration this was not the case with the genioglossus and inspiratory activity was not always seen in the genioglossus even during 10% CO2 administration. It is concluded that there are fundamental differences between the control of genioglossus and alae nasi activity in the fetal sheep. The alae nasi behaves as an inspiratory muscle responding to hypoxia and hypercapnia as would be expected but the genioglossus shows no inspiratory activity during normal unstimulated fetal breathing. Thus the neural mechanisms for activation of inspiratory activity appear to be present late in gestation. However it is possible for the genioglossus to develop an inspiratory rhythm under conditions of much increased respiratory drive.     

重症肺炎患者血清IL-2水平及与呼吸功能的相关性分析

目的:研究重症肺炎患者血清白细胞介素-2(IL-2)水平及与呼吸功能的相关性。方法:选择2013年5月~2016年5月在我院进行诊治的重症肺炎患者80例为观察组,同期在我院呼吸科入住的一般呼吸道感染患者80例为对照组,分别检测两组的血清IL-2水平,记录呼吸频率,取动脉血检测氧分压和氧合指数,采用单因素回归分析血清IL-2与呼吸功能的相关性。结果:观察组的血清IL-2水平明显高于对照组(P0.05);观察组的呼吸频率明显高于对照组(P0.05),氧分压和氧和指数均明显低于对照组(P0.05);血清IL-2水平与呼吸频率呈明显正相关(P0.05),与氧分压和氧和指数呈明显负相关(P0.05)。结论:重症肺炎患者血清IL-2水平明显升高,且与呼吸功能密切相关,能作为判断重症肺炎患者呼吸功能的客观检查指标。     

Total work rate of breathing optimization in CO-2 inhalation and exercise.

The hypothesis that respiratory frequency and the relative durations of inspiration and expiration are regulated according to a total cycle work rate minimization criterion was explored. Effects of negative work performed by the respiratory muscles and dead space variation as a function of tidal volume were included in a formulation which yielded a theoretically predictable optimal frequency and relative duration of inspiration and expiration at all levels of ventilation. Predicted cycle characteristics based on measured mechanical parameters were compared with data taken during CO-2 inhalation (3 and 5%) and moderate exercise (MRR = 3 and 6) in three normal human subjects. No major difference in breathing pattern was observed between CO-2 inhalation and exercise. Results suggest that conditions for minimization of total cycle work rate are achieved asympototically as the level of ventilation rises above the resting level. At rest and at low levels of hyperpnea complete work rate optimization is not achieved.     

Integrated approach for in vivo evaluation of respiratory muscles mechanics

The respiratory muscles constitute the respiratory pump, which determines the efficacy of ventilation. Any functional disorder in their performance may cause insufficient ventilation. This study was designed to quantitatively explore the relative contribution of major groups of respiratory muscles to global lung ventilation throughout a range of maneuvers in healthy subjects. A computerized experimental system was developed for simultaneous noninvasive measurement of inspired/expired airflow, mouth pressure and up to 8 channels of EMG surface signals from major respiratory muscles which are located near the skin (e.g., sternomastoid, external intercostal, rectus abdominis and external oblique) during various respiratory maneuvers. Lung volumes values were calculated by integration of airflow data. Hill's muscle model was utilized to calculate the forces generated by the muscles from the acquired EMG data. Analysis of EMG measurements and respiratory muscles forces revealed the following characteristics: (a) muscle activity increased with increased breathing effort, (b) inspiratory muscles contributed to inspiration even at relatively low flow rates, while expiratory muscles are recruited at higher flow rates, (c) the forces generated by the muscle depended on the muscle properties as well as on their EMG performance and (d) the pattern of the muscle's force curves varied between subjects, but were generally consistent for the same subject regardless of breathing effort.     

Regulation of respiration: visceral and behavioural components

The review segregates two aspects of respiration regulation: autonomous respiration regulation as a visceral function ensuring metabolic needs of a body by maintaining stability of own respiratory environment, on the one hand, and behavioural regulation of respiration under control of the volitional sphere, on the other hand. The authors focus on respiratory rythmogenesis, the problem that has not yet been resolved, and on the mechanism of precise correlation of lung ventillation with the metabolic level, in case of muscular exercise, in particular. The authors discuss interaction of visceral and behavioural mechanisms of respiratory regulation. The substance of the phenomenon of respiratory embarrassment is considered in this connection as a visceral signal addressed to the behavioural sphere. Reasonableness of introduction of a new breathing system in a healthy person is doubted. The article justifies the pracice of bioregulation of the respiratory function.     

Periodicities in respiration and heart rate in newborns

Periodic breathing is common in normal infants, but may be associated with prolonged apnea leading to crib death. The mechanisms of periodic breathing and its relation to normal breathing patterns are unclear. We recorded respiratory and heart rate (HR) patterns of 11 healthy newborn infants during quiet sleep, in both normal and periodic breathing. Spectral analysis of the respiratory pattern revealed a low-frequency (LF) periodicity in normal breathing approximately equal to the frequency of periodic breathing when this occurs. Periodic breathing thus appears to be an exaggeration of an underlying slow amplitude variation which is present in regular breathing. LF periodicity also appeared in the HR pattern in both normal and periodic breathing, suggesting an LF modulation of cardiovascular control as well. The lack of a definite phase relation between HR and ventilation at LF may indicate dominant peripheral, rather than central, interactions between HR and respiration at these frequencies.     

Respiratory muscle responses elicited by dorsal periaqueductal gray stimulation in rats

The periaqueductal gray matter is an essential neural substrate for central integration of defense behavior and accompanied autonomic responses. The dorsal half of the periaqueductal gray matter (dPAG) is also involved in mediating emotional responses of anxiety and fear, psychological states that often are associated with changes in ventilation. However, information regarding respiratory modulation elicited from this structure is limited. The present study was undertaken to investigate the relationship between stimulus frequency and magnitude on ventilatory pattern and respiratory muscle activity in urethane-anesthetized, spontaneously breathing rats. Electrical stimulation in the dPAG-recruited abdominal muscle activity increased ventilation and increased respiratory frequency by significantly shortening both inspiratory time and expiratory time. Ventilation increased within the first breath after the onset of stimulation, and the respiratory response increased with increasing stimulus frequency and magnitude. dPAG stimulation also increased baseline EMG activity in the diaphragm and recruited baseline external abdominal oblique EMG activity, normally quiescent during eupneic breathing. Significant changes in cardiorespiratory function were only evoked by stimulus intensities >10 microA and when stimulus frequencies were >10 Hz. Respiratory activity of both the diaphragm and abdominal muscles remained elevated for a minimum of 60 s after cessation of stimulation. These results demonstrate that there is a short-latency respiratory response elicited from the dPAG stimulation, which includes both inspiratory and expiratory muscles. The changes in respiratory timing suggest rapid onset and sustained poststimulus dPAG modulation of the brain stem respiratory network that includes expiratory muscle recruitment.     

Cardiac output and O2 consumption during inspiratory threshold loaded breathing

In this study, noninvasive measurements of cardiac output and O2 consumption were performed to estimate the blood flow to and efficiency of the respiratory muscles that are used in elevated inspiratory work loads. Five subjects were studied for 4.5 min at a respiratory rate of 18 breaths/min and a duty cycle of 0.5. Studies were performed at rest without added respiratory loads and at elevated inspiratory work loads with the use of an inspiratory valve that permitted flow only when a threshold pressure was maintained. Cardiac output and O2 consumption were calculated using a rebreathing technique. Respiratory muscle blood flow and O2 consumption were estimated as the difference between resting and loaded breathing. Work of breathing was calculated by integrating the product of mouth pressure and volume. Increases in cardiac output and O2 consumption in response of 4.5 min loaded breathing averaged 1.84 l/min and 108 ml/min, respectively. No increases were seen in response to 20-s loaded breathing. In a separate series of experiments on four subjects, though, cardiac output increased for the first 2 min then leveled off. These results indicate that the increase in cardiac output was a metabolic effect of the increased work load and was not caused primarily by the influence of the highly negative intrathoracic pressure on venous return. Efficiency of the respiratory muscles during inspiratory threshold loading averaged 5.9%, which was similar to measurements of efficiency of respiratory muscles using whole-body O2 consumption that have been reported previously in humans and in dogs.     

Apnoeic responses to intracarotid nicotine challenge in anaesthetized cats.

To determine the effects of an intraarterial administration of nicotine on the occurrence of apnoea and the activity of rib cage respiratory muscles, we studied 31 anaesthetized, spontaneously breathing cats. Phrenic activity was used as an index of neural inspiratory drive. Activity of parasternal intercostal (PIM) and triangularis sterni (TS) muscles was recorded. Nicotine in a dose of 65 microg/kg was injected into the left common carotid artery prior to and after midcervical vagotomy, preceded by section of the superior laryngeal nerves (SLNs). In eight additional cats, initially neurotomized as mentioned, nicotine was injected after bilateral disruption of the carotid sinus nerves (CSNs). Nicotine induced prompt expiratory apnoea of mean duration of 5.4+/-0.3s in 19 non-vagotomized and of 5.92+/-0.51 s (mean+/-S.E.M.) in 13 vagotomized cats. The occurrence and duration of the temporary arrest of breathing were reduced by midcervical vagotomy but not by subsequent CSNs neurotomy, which abolished post-apnoeic acceleration of breathing.In post-nicotine breathing of increased tidal volume and respiratory rate, peak activity of the parasternal intercostal muscles increased from baseline of 3.2+/-1.2 to 9.5+/-2.0 arbitrary units (p<0.001). The peak height of the phrenic nerve elevated from 7.9+/-0.9 to 14.5+/-1.7 arbitrary units (p<0.001). That of the triangularis sterni showed no change.The response of the respiratory effectors elicited by nicotine was independent of the vagal integrity and may be attributed to activation of nicotine receptors within the brainstem respiratory neurones.