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Abstract Effect of posture on the hypercapnic ventilatory response was studied on the anaesthetized rats by using rebreathing techniques in the supine and head-down positions. There were no statistically significant alterations in tidal volume, frequency, minute ventilation, and PETCO2 between the head-down and supine positions during breathing at rest. However, the esophageal pressure inspiratory swings were significantly greater in the head-down compared with supine position. Moreover, we found that body position did not affect the hypercapnic ventilatory response, but did affect the relationship between inspiratory driving pressure and the increase of end tidal PCO2. Greater inspiratory pressure is required to maintain the same level of the ventilatory response to hypercapnia in the horizontal position with the head-down. We believe that the discrepancy between postural alterations in the hypercapnic ventilatory and pressure responses is presumably a result of decreased lung compliance and increased airflow impedance of respiratory system in the head-down position.

Abstract It had been hypothesized that the regions of prefrontal cortex which are involved in respiratory control can modulate Hering-Breuer reflexes evoked by vagal input from pulmonary stretch receptors. In the present study, experiments were performed on urethane anesthetized spontaneously breathing Wistar rats. The expiratory-promoting reflex was evaluated from changes in expiratory time immediately after airway occlusion at the end of inspiration. The inspiratory-inhibitory reflex was estimated from changes in inspiratory time provoked by airway occlusion at the end of expiration. The results indicate that electrical microstimulation of the responsive sites within the insular cortex significantly weakened both expiratory-promoting and inspiratory-inhibitory reflex. Activation of the infralimbic cortex depressed expiratory-promoting reflex, but inspiratory-inhibitory reflex was enhanced. These results suggest that stimulation of the prefrontal cortex influences vagally mediated control of the respiratory phases timing and several regions of the prefrontal cortex modulate distinct sets of neurons in the network controlling inspiratory and expiratory phases of a breath cycle.

The goal of the current study was to identify the role of the glucocorticoids in the respiratory effects of proinflammatory cytokines. For this purpose intravenous injections of TNF-α were used in anesthetized spontaneously breathing rats before and after pretreatment of dexamethasone, a synthetic steroid with predominant glucocorticoid activity. Dexamethasone was injected intraperitoneally at a dose of 1 mg/kg. TNF-α was administrated into the tail vein at a dose of 40 mg/kg. We found that dexamethasone pretreatment eliminated the cytokine-induced increase in pulmonary ventilation and decrease in the hypoxic ventilatory response. Dexamethasone had a pronounced rapid effect on the respiratory activity of TNF-α as early as 30 minutes after administration. Therefore, we assume that this mechanism of action of dexamethasone was non-genomic, associated with the blocking of secondary mediators of the cytokine response., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To study the dynamics of hemorheologic changes and the frequency of early complications of laparoscopic radical hysterectomy in patients with uterine corpus cancer depending on conducting rehabilitation activities in the early postoperative period., Material and Methods: The number of patients with uterine corpus cancer equal 49 (mean age 54.8±2.2 years), divided into 2 comparable groups, was examined: experimental group - 23 patients, who received local magnetotherapy since the first day after surgery for 5-6 days, and control group - 26 patients without physiotherapy. Comparative group included 24 healthy women. The basic rheological parameters, namely blood viscosity at high and low shear rate, hematocrit, erythrocytes' aggregation and deformability, erythrocytes and platelets electrophoretic mobility, were evaluated in all patients initially, on the 1st and 5th days after surgery and in comparison group., Results: There were changes in the rheological properties of the blood before surgery in patients of both groups: increase of blood viscosity, enhancement of aggregation activity of its formed elements, decrease of erythrocytes' deformability properties. The laparoscopic radical hysterectomy was accompanied by the exacerbation of these disorders. The early magnetotherapy in patients reduced hemorheological abnormalities up to the preoperative parameters ( p <0.05) for 5 days, as well as reduced the incidence of early postoperative complications by 2.4 times compared to the control group., Conclusion: The application of local low-frequency low-intensity magnetotherapy since the first postoperative day allows to reduce the level of postoperative hemorheological abnormalities up to the level of preoperative parameters, as well as the frequency of early postoperative complications.

Chronic arterial insufficiency of lower limbs (CAILL) is a common cardiovascular disease that affects 200 million subjects worldwide: from 4 to 12% of people aged 55-70 years and 20% - over 70 years. The cause of blood circulation disorder in this disease is usually a complex of pathological changes including abnormality of vessel walls' anatomical structure or integrity, disorder of blood rheological properties and alterations of its thrombotic potential. Thus, the therapy of patients with CAILL aiming at hemostasis and, in particular, platelets' aggregation is one of the most urgent problems of medicine., Objective: To study the effectiveness of blue range visible radiation combined with basic therapy to improve hemostasis in patients with CAILL., Material and Methods: The number of male patients with CAILL equal 63 aged 43-57 years was examined. Blood flow parameters on a fixed part of femoral artery outside the occlusion area were registered based on subjective criteria, number of painless steps and ultrasound doppler flowmetry according to the Fontaine-Pokrovsky classification. The second degree of ischemia was diagnosed in 38 patients, the third degree - in 25 patients. All patients received basic pharmacotherapy. Patients were divided into 2 groups by simple randomization method: control group included 18 patients with II degree of ischemia and 12 patients with III degree of ischemia who received basic pharmacotherapy combined with photohemotherapy (PHT). A set of commonly used laboratory methods for examination of blood coagulation system was applied to assess the effectiveness of PHT. The number of apparently healthy people equal 26 was examined to evaluate normal value of hemostasiological parameters., Results: Basic pharmacological treatment had a certain positive effect on studied hemostasis parameters and its thrombotic component. However, they did not differ statistically significantly from similar parameters before treatment on the 14th day after treatment. As a result of comprehensive therapy the changes in hemostasis system had identical and statistically significant in percentage terms changes compared to norm and baseline in patients' subgroups of study group with II and III degrees of ischemia. In addition, most hemostasis parameters in patients with II degree of ischemia were close to those of apparently healthy volunteers. Hemostasis parameters in patients with III degree of ischemia decreased to the levels of patients with II degree of ischemia before treatment., Conclusion: The use of basic pharmacological therapy with optical exposure to blood by blue light allows to correct hemostasis and its thrombotic component in patients with CAILL.

TNF-α is the key inflammatory cytokine. TNF-α receptors are expressed in brain stem regions involved in respiratory control and also in the carotid bodies, which are the sensory organs monitoring arterial blood O 2 . We hypothesised that the circulating tumour necrosis factor (TNF)-α may affect the lung ventilation and modulate the hypoxic ventilatory response via activation of cyclooxygenase (COX) and nitric oxide synthase (NOS) pathways. The aim of the current study was to compare the respiratory effects of TNF-α before and after pretreatment with diclofenac or L-NG-nitro arginine methyl ester (L-NAME) nonspecific inhibitors of COX and NOS, respectively. The hypoxic ventilatory response was measured in anaesthetised rats using rebreathing techniques. We found that TNF-α increased the lung ventilation in normoxia but decreased the ventilatory response to hypoxia. Pretreatment with each of these inhibitors reduced respiratory effects of TNF-α. We believe that activation of COX and NOS-related pathways and also "cross-talk" between them mediates the TNF-α respiratory effects and underlies the impact of inflammation on the respiratory function., (Copyright © 2020 Elsevier B.V. All rights reserved.)

It is known that the maximum mouth inspiratory pressure (MIP) and expiratory pressure (MEP) vary with age, weight, height, and skeletal muscle mass. However, the influence of physical training on ventilatory function outcomes is an area of limited understanding. The aim of this study was to investigate the respiratory muscle strength and its relation to spirometry variables in untrained healthy persons versus trained athletes. MIP and MEP were assessed in 22 power athletes and 28 endurance athletes, and in 24 age- and sex-matched normal healthy subjects (control group). The measurement was done with a mouth pressure meter. We found that respiratory muscle strength and ventilatory function in endurance athletes were outstandingly superior to that in power athletes; the latter's muscle strength was better than that of healthy untrained controls. Both MIP and MEP significantly correlated with the maximum voluntary ventilation (MVV) in both power athletes and controls, but not so in endurance athletes. The corollary is that the intensive endurance training could result in the improvement of respiratory muscle strength, meeting the maximum upper limit of functional reserve of respiratory muscles and the corresponding ventilation. On the other hand, targeted training of respiratory muscle strength may be an effective strategy to increase ventilatory function in power athletes, particularly those having a low maximum inspiratory and expiratory pressure, and in less physically fit healthy persons.

A pressing issue of the day is the identification of therapeutic targets to suppress the "cytokine storm" in COVID-19 complicated by acute respiratory distress syndrome (ARDS) with concomitant hypoxemia. However, the key cytokine and its relative contribution to the pathogenesis of ARDS, which leads to high mortality, are unknown. A comparative assessment of the effect of elevated systemic levels of pro-inflammatory cytokines IL-1β, TNF-1α and IL-6 on the respiratory patterns and survival rate in rats was carried out under progressively increasing acute hypoxia. Increasing hypoxia was simulated by a rebreathing method (from normoxia to apnea). The recorded parameters were the breathing pattern components (tidal volume and respiratory rate), minute ventilation (MV), oxygen saturation, apnea onset time, and posthypoxic survival rate. A comparative analysis was carried out under mild, moderate and severe hypoxia (at F I O 2 = 15, 12 and 8%, respectively). It was shown that increasing hypoxia was accompanied by an acute suppression of the compensatory elevation of MV in rats with increased systemic levels of IL-1β and TNF-1α. By contrast, IL-6 caused an intensive elevation of MV with increasing hypoxia. Acute hypoxia (F I O 2 < 8%), in all experimental series, was accompanied by an impairment of the respiratory rhythm up to the development of apnea. Posthypoxic breathing restoration (survival rate) was 50% with IL-1β and TNF-1α and only 10% with IL-6. The obtained results indicate that the elevated IL-6 level, despite the absence of respiratory disorders at the initial stage of the developing pathologic process, leads to a higher mortality in rats compared to IL-1β and TNF-1α. This allows considering IL-6 as an early prognostic biomarker of a high risk of mortality under severe hypoxemia., Competing Interests: CONFLICT OF INTERESTThe authors declare that they have neither evident nor potential conflict of interest related to the publication of this article., (© Pleiades Publishing, Ltd. 2021.)

We studied the effect of increased systemic levels of the proinflammatory cytokine IL-1β on the vasomotor reactions of pial microvessels in anesthetized rats under conditions of experimentally simulated progressively increasing acute normobaric hypoxia. Vital microscopy showed that more pronounced dilatation of pial vessels in response to IL-1β under hypoxic conditions was almost completely prevented by pretreatment with non-specific NO synthase blocker L-NAME. These findings indicate the involvement of NO-dependent mechanisms in the vasodilator effect of proinflammatory cytokines under conditions of acute hypoxic exposure.

Introduction: Myocarditis is one of the most urgent and in many respects unresolved problems in cardiology. The situation is further aggravated by the ever increasing incidence of the of disease. The lack of knowledge about myocarditis etiology and pathogenesis creates a number of difficulties for the choice of the adequate treatment strategies., Aim: The objective of the present study was to evaluate the effectiveness of quantum photohemotherapy (PHT) with the use of a blue light in the combined treatment of infectious-allergic myocarditis (IAM)., Material and Methods: We examined a total of 28 patients including 12 women and 16 men at the age from 16 to 45 years suffering from IAM. The diagnosis of IAM was confirmed clinically, biochemically, and functionally with the application of the blood tests, chest X-ray examination, echo- and electro-cardiography. We used the classification of N.R. Paleev and M.A. Gurevich for myocarditis diagnostics. The diagnosis of ischemic heart disease was excluded according to the WHO criteria. The degree of heart failure in the patients was assessed based on the NYHA classification criteria. All the patients were given therapy with nonsteroidal anti-inflammatory drugs, metabolic drugs, anti-arrhythmics, diuretics, and angiotensin converting enzyme inhibitors. In addition, the generally accepted methods for the characteristic of blood rheological properties were employed. Moreover, the universally recognized rehabilitative and therapeutic measures were supplemented by blue light PHT using an AFS-Solaris light-emitting diode for intravascular irradiation of blood through the disposable light guides., Results: The study has demonstrated that IAM was accompanied by a number of hemorheological disorders that collectively make up a component of pathogenesis of the condition in question. The application of blue light PHT for the combined treatment of the patients with IAM led to the improvement in their rheological status and peripheral blood characteristics., Conclusion: Various hemorheological disorders were diagnosed in the patients suffering from infectious-allergic myocarditis. The main effect of blood viscosity reduction documented in the patients with IAM under the influence of blue light PHT was attributable to the reduction in hematocrit decreasing and suppression of the erythrocytes aggregation activity.

We investigated the effect of the major inflammatory cytokine interleukin-1beta (IL-1β) on the ventilatory response to hypoxia. The goal was to test the hypothesis that IL-1β impairs the hypoxic ventilatory response in vivo by indirectly inhibiting respiratory neurons in the brainstem via prostaglandins. Thus, IL-1β was delivered by cerebroventricular injection, and the ventilatory hypoxic response was assessed in anesthetized, spontaneously breathing rats pretreated with or without diclofenac, a nonspecific inhibitor of prostaglandin synthesis. We found that the slope of the ventilatory response to hypoxia decreased almost 2-fold from 10.4 ± 3.02 to 4.06 ± 0.86 mL·min -1 ·(mm Hg) -1 (-61%) 90 min after administration of IL-1β (p < 0.05). The slope of tidal volume and mean inspiratory flow also decreased from 0.074 ± 0.02 to 0.039 ± 0.01 mL·(mm Hg) -1 (-45%, p < 0.05), and from 0.36 ± 0.07 to 0.2 ± 0.04 mL·s -1 ·(mm Hg) -1 (-46%, p < 0.05), respectively. Pretreatment with diclofenac blocked these effects. Thus, the data indicate that IL-1β degrades the ventilatory hypoxic response by stimulating production of prostaglandin. The increase of cerebral levels of IL-1β, which is induced by the activation of immune cells in the brain, may impair respiratory chemoreflexes.

Under a progressive growth of acute hypoxia the effect of high systemic levels of proinflammatory cytokine interleukin-1 Р (IL-1Р) were studied the reactions of the cardiorespiratory system of anesthetized Wistar rats. The results suggest a negative effect of IL-1 Р on the control mechanisms the respiratory and cardiovascular system, which was reflected in the reduction of resistance to acute hypoxia and the ability to spontaneous autoresuscitation after apnea in posthypoxic period, as well as in the development of circulatory collapse. It is assumed that the basis of the resistance mechanisms of the body to reduce the hypoxic exposure is multifactorial effects of increased levels of IL-1 Р, activation of HIF-1 a and NO production in the operation of the systems responsible for maintaining oxygen homeostasis.

As a part of the multi-disciplinary "SELENA-T"-2015 Bed Rest Study, we investigated the pattern of inspiratory muscles fatigue in 22 healthy male subjects during incremental exercise test to exhaustion before and after 21 days of hypokinesia evoked by bed rest. Hypokinesia consisted of head-down bed rest (HDBR) at a minus 6° angle, simulating microgravity present on orbiting spacecraft, in 10 subjects. The remaining 12 subjects spent the first 5 days of hypokinesia in HDBR position and the subsequent 16 days in head-up bed rest (HUBR) at a plus 9.6° angle, as a presumed analog of lunar gravity that is six times less than Earth's gravity. Maximal inspiratory pressure (MIP) and electromyograms (EMG) of the diaphragm (D), parasternal (PS), sternocleidomastoid (SCM), and scalene (S) muscles served as indices of inspiratory muscle function. Before both HDBR and HUBR, exercise decreased MIP and centroid frequency (fc) of EMG (D, PS, SCM, and S) power spectrum (p < 0.05). After 3 weeks of HDBR, but not HUBR, inspiratory muscles fatigue was more expressed compared with control (p < 0.05). We conclude that HDBR lowers inspiratory muscles resistance to fatigue during high-intensity exercise while HUBR has no such effect. These changes may limit maximal ventilation and may contribute to exercise intolerance observed after prolonged simulated microgravity. The physiological mechanisms of respiratory muscle dysfunction after HDBR consist primarily of postural effects, and are not due only to hypokinesia.

The role of NO-ergic mechanisms in the realization of the respiratory effects of pro-inflammatory cytokine IL-1beta was investigated in acute experiments on anesthetized rats. To achieve this, we studied the effect of intravenous administration of IL-1beta during inhibition of NO-synthase by N-nitro-L-arginine methyl ester (L-NAME, a non-specific blocker of NO-synthase) on the parameters of breathing and the Hering-Breuer inspiratory-inhibitory reflex. It was shown that the effect of L-NAME eliminates the IL-1beta-dependent increase of the Hering-Breuer reflex, whereas effects on breathing pattern does not change: the increase in IL-1beta system-level evokes an increase in respiratory rate, tidal volume and lung ventilation. It is assumed that one of the mechanisms of enhance in the strength inspiratory-inhibitory reflex by increasing circulatory IL-1beta level is the increased glutamate-ergic transmission on pump-neurons induced by increase in nitric oxide synthesis in cerebrovascular endothelial cells. In conclusion, NO-ergic mechanisms participate in the modulation of the vagal respiratory reflexes during the development of the acute phase of systemic inflammation.

This study explores the hypothesis about the possible involvement of the cyclooxygenase pathway in the effects of interleukin-1beta (IL-1β) on the breathing pattern and Heuring-Breuer respiratory reflexes. Respiratory frequency (fR), tidal volume (VT) and esophageal pressure were recorded in 29 adult male Wistar rats anaesthetized with urethane. Heuring-Breuer reflexes were tested by airway occlusion at achieving functional residual capacity (inspiratory-inhibitory reflex), and at the height of inspiration (expiratory-promoting reflex). It had been shown that an elevation of IL-1β in the systemic circulation causes an increase in VT, fR, lung ventilation and strengthens respiratory reflexes. These respiratory effects had not been shown if IL-1β administered after intraperitoneal injection of diclofenac, which had not any significant respiratory effects by itself. Because diclofenac is a non-specific antagonist of cyclooxygenases, it had been concluded that the prostaglandins mediate respiratory effects of IL-1β in point of fact.

The interdependent reactions of the cardiorespiratory system during experimental simulation of progressive acute hypoxia were studied in anesthetized Wistar rats. The results indicate that the extremely low oxygen content in the inhaled gas mixture to less than 6% lead to terminal sedation and apnea. After the cessation of hypoxic exposure were observed spontaneous autoresuscitation. Effects of progressive hypoxia, is an example of a multi-component interdependent reactions of the cardiorespiratory system, which are based on the respiratory and vasomotor center function disturbance and the predominance of parasympathetic influences on the heart. The obtained data can be used as a model of hypoxic apnea to examine the influence of physiologically active substances on the cardiorespiratory system at disease pathology.

The purpose of this article is to review experimental data proving that the insular cortex is involved in the regulation of visceral systems: respiratory, cardiovascular and gastrointestinal systems. The paper deals with the data on the structure of the insular cortex, the pathways in brain by which visceral information ascend to the insular cortex, the results of neurophysiological experiments and clinical observations. The experimental evidence of viscerotopical organization of not only sensor, but also motor representation of visceral systems in the insular cortex is discussed. On the basis of these data the insular cortex is defined as sensorimotor visceral cortex. It is demonstrated that one of the mechanisms of influence of the insular cortex on the regulation of internal organs is the modulation of reflex reactions which take place at the bulbar level.

At the present time very little is known about interactions between the systemic inflammatory and ventilatory control. Our previous study has demonstrated that the elevation of the major inflammatory cytokines interleukin-1β (IL-1β) in the cerebrospinal fluid (CSF) may affect the control of ventilation. The aim of the current study was to compare the respiratory effects of IL-1β before and after pretreatment with diclofenac, a nonspecific cyclooxygenase (COX) inhibitor. Using the method of rebreathing with hyperoxic gas mixture we demonstrate that the slope of the ventilatory response to carbon dioxide decreased almost twofold from 5.6±0.52 to 2.5±0.28 ml min(-1)mmHg(-1) (p<0.01) 40 min after cerebroventricular administration of IL-1β. In contrast, the basal level of lung ventilation increased after the elevation of IL-1β in CSF. Diclofenac pretreatment eliminated these respiratory effects of IL-1β. The data indicate that the ability of IL-1β to enhance basal ventilation and to reduce the ventilatory hypercapnic response is mediated by the COX pathway., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The compensatory responses of the respiratory system to simulated central hypervolemia (CHV) were investigated in 14 normal subjects. The central hypervolemia was caused by a short-time passive head-down tilt (HDT, -30°, 30 min). The results show that CHV increased the mechanical respiratory load and the airway resistance, slowed the inspiratory flow, increased the duration of the inspiratory phase, reduced the respiratory rate, but not changed the minute ventilation. CHV induced a significant rise in inspiratory swings of alveolar pressure (184%), based on the inspiratory occlusion pressure measurement. These changes indicate a compensatory increase in the inspiratory muscle contraction force. A stable level of minute ventilation during CHV was an effect of increased EMG activity of parasternal muscles more than twice (P<0.01). A contribution of the diaphragm and scalene muscles to ventilation during spontaneous breathing in HDT was reduced. An increase of genioglossus contractile activity during HDT contributed to the stabilization of airway patency. These results suggest that a coordinated modulation of inspiratory muscles activity allows preserving a constant level of minute ventilation during a short-time intrathoracic blood volume expansion. The mechanisms of respiratory load compensation seem to be mediated by afferent information from the lung and respiratory muscle receptors and from the segmentary reflexes and intrinsic properties of the muscle fibers.

The aim of this study was to assess the effect of inspiratory muscle training (IMT) on resistance to fatigue of the diaphragm (D), parasternal (PS), sternocleidomastoid (SCM) and scalene (SC) muscles in healthy humans during exhaustive exercise. Daily inspiratory muscle strength training was performed for 3 weeks in 10 male subjects (at a pressure threshold load of 60% of maximal inspiratory pressure (MIP) for the first week, 70% of MIP for the second week, and 80% of MIP for the third week). Before and after training, subjects performed an incremental cycle test to exhaustion. Maximal inspiratory pressure and EMG-analysis served as indices of inspiratory muscle fatigue assessment. The before-to-after exercise decreases in MIP and centroid frequency (fc) of the EMG (D, PS, SCM, and SC) power spectrum (P<0.05) were observed in all subjects before the IMT intervention. Such changes were absent after the IMT. The study found that in healthy subjects, IMT results in significant increase in MIP (+18%), a delay of inspiratory muscle fatigue during exhaustive exercise, and a significant improvement in maximal work performance. We conclude that the IMT elicits resistance to the development of inspiratory muscles fatigue during high-intensity exercise.

Respiratory muscle fatigue can develop during simulated airway obstruction. The aim of this study was to characterize the pattern of inspiratory muscle fatigue and to assess the resistance to fatigue of diaphragm (D), parasternal (PS), sternocleidomastoid (SM) and scalene (SC). 8 healthy untrained subjects participated in this study. To identify signs of inspiratory muscles fatigue development electromyographic activity of D, PS, SCM and SC was recorded during 5-min exercise with loaded breathing (40 cm H2O/L · s(-1)). The before-to-after exercise measurements of maximal inspiratory pressure (MIP) and EMG power spectrum changes were performed. Maximal inspiratory pressure declined about 12% after exercise test compared with control, whereas the peak magnitude of integrated electrical activity of D, PS, SCM and SC during post-exercise Muller's maneuver was significantly greater than in pre-exercise test in all subjects. The extent ofinspiratory muscles fatigue was evaluated by analysis of shift in centroid frequency (fc) of EMG power spectrum. All subjects demonstrated a significant reduction in fc of PS, SCM and SC.fc of D was not changed. Diaphragm is more resistantto fatigue during obstructive breathing compared with PS, SCM and SC. The data suggest that the reduction of maximum inspiratory pressure in chronic obstructive pulmonary disease also caused primarily by the weakening of the accessory muscles, while the weakness of the diaphragm may occur in the later stages of the disease. The functional failure of accessory muscles is an additional factor, which, along with the additional breathing resistance increases the load on the diaphragm, promoting its fatigue and reduced respiratory reserve.

We evaluated the maximal mouth inspiratory pressure and the EMG patterns of major respiratory and accessory muscles used in the generation of voluntary inspiratory maneuvers during different body positions. Ten healthy subjects (F/M-4/6), the mean age 22.000B10.6 years, participated in the study. The maximal inspiratory mouth pressure (MIP) during Müller's maneuver was measured from residual volume in the standing, sitting, right-sided (RSL) and left-sided lying (LSL), supine, and head-down-tilt (HDT) (3000B0; relatively horizon) positions. EMG of the diaphragmatic (D), parasternal (PS), sternocleidomastoid (SM), and genioglossus (GG) muscles were assessed in each body position. The baseline MIP was 105.3 00B1; 12.0 in men and 59.9 00B110.1 cmH(2)O in women in the standing position and did not appreciable differ in the other positions, except the HDT where it was lower by 23 and 27% in men and women, respectively (P003C0.05). During Müllers maneuver, diaphragmatic EMG activity also was similar in all the body positions, but it was significantly enhanced in the HDT. In contrast, PS EMG showed the highest level of activation in the standing position, taken as the control, reference level, and was lower in the HDT. Activation of SM during the maneuver was near the control in the sitting position, lower in the supine (79%), RSL (85%), LSL (80%), and HDT (72%) positions (P 003C0.05). GG EMG was significantly greater during maximal inspiratory effort in the supine and HDT positions (125and 130%, respectively), while it was lower in the sitting, LRS, and LLS positions (76, 57, and 43%) compared with standing (P 003C; 0.05). We conclude that the inspiratory pressure generated during Muller maneuver is a reflection of complex interactions between several muscle groups during changes in body positions.

The aim of this study was to characterize the pattern of inspiratory muscle fatigue and to assess the resistance to fatigue of the diaphragm (D), parasternal (PS), sternocleidomastoid (SCM), and scalene (SC) muscles. Nine healthy, untrained male subjects participated in this study. Electromyographic activity (EMG) of D, PS, SCM, and SC was recorded during an incremental cycling test to exhaustion (workload of 1.0 W/kg with 0.5 W/kg increments every 5 min). The before-to-after exercise measurements of maximal inspiratory pressure (MIP) and EMG power spectrum changes were performed. The maximal inspiratory pressure declined about 8.1 % after exercise compared with that in the control condition (124.3 ± 8.5 vs. 114.2 ± 8.9 cmH2O) (P > 0.05), whereas the peak magnitude of integrated electrical activity of D, PS, SCM, and SC during the post-exercise Müller maneuver was significantly greater in all subjects than that pre-exercise. The extent of inspiratory muscles fatigue was evaluated by analysis of a shift in centroid frequency (fc) of EMG power spectrum. Exercise-induced D fatigue was present in three subjects and PS fatigue was another in two; whereas both D and PC fatigue were observed in four subjects. All subjects demonstrated a significant reduction in fc of SCM and SC. Results indicate that early signs of the fatiguing process might be detected in the D, PS, SCM, and SC muscles during exercise to exhaustion. Fatigue of either D or PS muscles develops selectively or together during exhaustive exercise, depending on the recruitment pattern of respiratory muscles. Accessory inspiratory muscles of the neck are less resistant to fatigue compared with the D and PS muscles.

A cerebral level of glutamate is one of the determinants of the central mechanisms of respiratory control. It had been hypothesized that endogenous glutamate could have a modulating effect on the functioning of mechanisms for neural control of respiratory function. Acute experiments on spontaneuosly breathing, urethane-anesthetized rats had been performed to study the respiratory effects of cerebroventricular microinjection of glutamate. It has been shown that a higher level of cerebral glutamate increases breathing rate and electrical activity of the diaphragm, and strengthen the Hering-Breuer reflex. These effects had a clear character of the phase. The results confirm the hypothesis suggested and prove that the increase in cerebral levels of glutamate leads to the activation of glutamate receptors of various types.

This review summarizes and analyzes the results of the present experimental studies indicating immune system involvement in control of breathing. The hypothesis about the role of cytokines in the mechanisms of respiratory muscle fatigue and reduced ventilatory sensitivity to hypercapnia during respiration with the added resistive loading is justified. The possible ways of implementing of respiratory cytokine effects are discussed.

The effect of head-down tilt on respiration and diaphragmal and parasternal muscles activity was investigated in 11 healthy subjects. The short-time (30 min) head-down tilt posture (-30 degrees relatively horizont) increased the inspiratory time (P < 0.05), decreased breathing frequency (P < 0.05), inspiratory and expiratory flow rate (P < 0.05) and increased the airway resistance (P < 0.05) compared with values in vertical posture. There were no significant changes in tidal volume and minute ventilation. Constant values of tidal volume and minute ventilation during head-down tilt were provided by increasing in EMG activity of parasternal muscles more then twice. It was established that the contribution of chest wall inspiratory muscles increased while the diaphragm's contribution decreased during head-down spontaneous breathing. Maximal inspiratory effort (Muller's maneuver) during head-down tilt evoked the opposite EMG-activity pattern: the contribution of inspiratory thoracic muscles was decreased and diaphragm's EMG-activity was increased compared with vertical posture. These results suggest that coordinate modulations in inspiratory muscles activity allows to preserve the functional possibility of human inspiratory muscles during short-time head-down tilt.

Research on studying influence of the rate of muscular training in conditions of additional resistive resistance to breath on a level of physical working capacity, aerobic productivity and a functional condition of system of breath was performed. It is shown, that regular muscular loadings in a combination to resistive resistance to breath in a mode of an interval exposition provide an increase of profitability and efficiency of functioning of breathing system as expressed in increase of expiratory force respiratory muscles, rationalization of parity of volumetric-time parameters of breath pattern that promotes more effective gas exchange and decrease in power cost of respiratory movements and as a result leads to increase in aerobic productivity and growth of the general and special working capacity. At continuous exposition of resistive resistance against a background of muscular training, the increase of inspiratory force of respiratory muscles, increase of functional capacity of system of breath were revealed at physical activity as well as a significant gain of the general physical working capacity.

Objective: Oxidative stress developed at several disease states and strenuous resistive breathing lead to the elevation of plasma and cerebral levels of proinflammatory cytokines. We hypothesized that the elevation of the cytokine level in body fluids would modulate breathing pattern and the ventilatory response to stimulation of central chemoreceptors by hypercapnia. -, Material and Methods: In experiments on anesthetized, tracheostomized, spontaneously breathing rats, the effects of intracerebroventricular injection of the human recombinant interleukin-1β (IL-1β) (0.5 μg/rat) on breathing were studied. -, Results: During resting breathing IL-1β evoked a significant increase in minute ventilation and in mean inspiratory flow. Furthermore, injection of IL-1β into the cerebral-spinal fluid decreases the responses of ventilation, tidal volume, and of mean inspiratory flow to carbon dioxide. -, Conclusions: The elevation of a proinflammatory cytokine in cerebrospinal fluid intensifies ventilation by modulation of breathing pattern, but weakens the chemoreflex sensitivity to hypercapnia. The results suggest the participation of cytokines in the central control of breathing and in the mechanisms of central chemoreception.

The effect of hypercapnic ventilatory response was examined in anaesthetized spontaneously breathing rats by using rebreathing techniques both at supine and -30 degrees head-down tilt positions. No significant differences were found in the minute ventilation response between the supine and head-down positions during hypercapnic stimulations. In contrast, we found that hypercapnia-stimulated breathing affected the relationship between deltaPoes and deltaP(ET), CO2. This study demonstrates that higher peak deltaPoes was developed in order to maintain the same ventilation in the supine and head-tilt position. The higher deltaPoes/deltaP(ET), CO2 head-down ratio than the supine was a result of increased airflow impedance of the total respiratory system while head-down. It is concluded that ventilation at head-down is regulated in such a way as to maintain the pH and Paco, despite mechanical loading imposed by the environment. Hence, during hypercapnic stimulation the ventilatory response in head-down position is shaped by interaction of chemical drives and mechanical afferent information arising.

Acute experiments on rats were performed to study the effects of intraventricular microinjections of gamma-aminobutyric acid (GABA) on the volume-time parameters of external respiration and the inspiration-inhibiting Hering-Breuer reflex. The state of this reflex before and after GABA administration was assessed in terms of the extent of changes in the duration and amplitude of inspiratory oscillations in intrathoracic pressure in response to end-expiratory occlusion of the trachea. Administration of 20 microM GABA into the lateral ventricles of the brain decreased the minute ventilation (due to reductions in the respiratory frequency and respiratory volume), weakened respiratory muscle contractions, and decreased the peak airflow rate on inspiration and expiration. The response to end-expiratory occlusion decreased significantly after administration of GABA, demonstrating the involvement of GABAergic mechanisms in mediating the inspiration-inhibiting Hering-Breuer reflex.

The aim of the present study was to determine the development of the inspiratory muscle fatigue in healthy human during incremental cycling to exhaustion under mild and heavy resistive loaded breathing in air and oxygen. Minute ventilation, tidal volume, respiratory rate, inspiratory mouth pressure, and parasternal EMG activities were recorded during an incremental cycling test under mild (12 cmH(2)O x l(-1) x s(-1)) and heavy (40 cmH(2)O x l(-1) x s(-1)) resistive loading in air and oxygen in 8 men. The degree of inspiratory muscle fatigue was evaluated by analysis of the dynamics of inspiratory mouth pressure, 'tension-time' index, and the fall of the high-to-low (H/L) ratio of the parasternal EMG. It was found that oxygen breathing slowed the development of inspiratory muscles fatigue evoked by incremental cycling only during mild resistive loading, whereas hyperoxia had not influence on inspiratory muscle endurance during heavy resistive loading.

The object of the the present study involved determining of rate of the inspiratory muscles fatigue development in healthy humans during increasing exercise under resistive loaded breathing with the air, oxygen, or hypoxic gas mixtures (FIO2 = 0.21, 1.0 and 0.13 respectively). 6 normal male subjects were studied. Volume/time parameters of breathing and parasternal integrated EMG activities were recorded under inspiratory-expiratory resistive loading 12 cm H2O/I s(-1) during increasing exercise in the air, oxygen, or hypoxic gas mixtures. The degree of inspiratory muscle fatigue was assessed by the "tension-time" index P(ml)/P(ml max) Tl/T(T) as well as by ratio of the mean amplitudes of the EMG signal spectrum in the hight-frequency (H) range to the mean spectrum amplitudes in the low-frequency (L) range (H/L). The signs of inspiratory muscle fatigue were most conspicuous during inhalation of the hypoxic mixture, compared to air. This was supported by the increased "tension-time" index, the hurried shallow breathing, and the decreased H/L ratio on 37% (p < 0.001). Only starting signs of inspiratory muscle fatigue were revealed during oxygen inhalation, although the maximum working capacity was higher than the control one (exercise in air). The results indicate that the oxygen contained in the inhaled gas mixture affects on the total working capacity total working capacity and influences the rate of inspiratory muscle fatigue development in exercising healthy men during resistive load 12 cm H2O/l s(-1). The decreased energy supply to respiratory muscles accelerates functional failure and results in fatigue, whereas the increased energy supply decelerates the development of inspiratory muscle fatigue.

In acute experiments on rats, effects of cerebro-ventricular microinjections of the gamma-aminobutyric acid (GABA) in the ventilation and Hering-Breuer inspiratory-inhibitory reflex were studied. Alteration of this reflex was estimated by changing in amplitude and duration of the esophageal pressure inspiratory oscillations after tracheal occlusion which was made at the moment of the end of expiration. It has been found that injection of 20 microM of GABA into the lateral ventricle produced a decrease of ventilation in result of diminished respiratory rate and tidal volume and weakening of the inspiratory muscle contractions. The GABA injection significantly decreased the respiratory response to occlusion and therefore it seems that GABA receptors take part in the Hering-Breuer inspiratory-inhibitory reflex.

The ventilatory response to isocapnic hypoxia was studied using rebreathing techniques in anesthetized and tracheostomized rats both in supine and in head-down tilt position (HDT-30 degrees). Hypoxic responses were calculated by the slope of ventilation against end tidal P(A)O2. The end-tidal P(A)CO2 was kept constant by varying expired gas flow through a CO2-absorbing bypass. The rebreathing was continued until P(A)O2 had fallen to between 70 +/- 3 and 50 +/- 2 mm Hg. The obtained results demonstrated that the maximal minute lung ventilation was 269 +/- 30 % during rebreathing test in supine position and 117 +/- 21% in the head-down tilt. It was also shown that the slopes of the relationship between minute ventilation and the decrease of end tidal P(A)O2 was 3-fold greater in supine than in HDT. The body position seems to affect the ventilatory response to isocapnic progressive hypoxia. In general, it may be a result of hemodynamic conditions alteration which increased respiratory resistive loads, changed the functional condition of carotid hemoreceptors and baroreceptor activity that modulate ventilatory response to chemoreceptor stimulation.

The role of lung receptors in respiratory control during acute head-down tilt (AHDT, -30 degrees) was investigated in anesthetized, tracheostomized rats. The results show that AHDT increased the mechanical respiratory load, slowed inspiratory flow, reduced the end expiratory lung volume, tidal volume and minute ventilation. On the other hand, during AHDT a significant rise in inspiratory swings of oesophageal pressure was recorded indicated a compensatory increase in inspiratory muscle contraction force. These effects were reduced after transaction of the vagus nerve. It was also shown that respiratory response on added mechanical load was reduced during AHDT as compared with the value in horizontal position. This deference disappeared after vagotomy. The data obtained suggested that afferent information from lung receptors take part in compensation of respiratory effects of AHDT. The cause of reduction in respiratory response to loading during AHDT involves weakness of lung reflexes evoked by volume changes.

This article reviews experimental studies of pharyngeal muscles with emphasis on m. genioglossus as a major muscle dilating pharynx and discusses neuromuscular mechanisms that maintains patency of upper airway. Mechanisms of inspiratory activation of genioglossus muscle in comparative with diaphragm are also discussed. Experimental data suggesting that upper airway muscles have a significant role in compensation of added inspiratory load are presented. It allows to regard pharyngeal dilating muscles as accessory muscles of respiration. Activation of m. genioglossus (together with others muscles dilating the pharynx) decreases airway resistance and thereby facilitates the load compensation function of "pumping" muscles. Similar to diaphragm involvement of the pharynx dilating muscles in the load compensatory response is resulted from a complex integration of several influences originating from mechano- and chemoreceptors.

The effects of long-term (21 days) head-down (-30 degrees) hypokinesia (HDH) on respiratory system and a functional state of diaphragm were investigated in rats. Minute ventilation, oesophageal and abdominal pressure, integrated electrical activity of diaphragm were measured in control and experimental group (after 21 days of HDH) of animals. The measurements were made in several body positions atresting and in occlusion breathing. The results indicate that HDH causes reduction in minute ventilation of lungs, decrease in orthostatic stability and functional reserve of the respiratory system capacity. It was established that the basic mechanism of HDH respiratory effects is contractile failure of diaphragm related to damage in excitation-contraction coupling in its muscular fibres.

The present study was undertaken to determine the mechanisms underlying the involvement of upper airway dilating muscles in compensatory responses to added inspiratory resistive load. Experiments were performed in tracheostomized, anaesthetised rabbits. The effect of inspiratory resistive loading on the electromyographic activity of the genioglossus muscle, the major dilating muscle of the pharynx, was studied in vagotomized and vagally intact rabbits during spontaneous breathing with a hypoxic gas mixture (10% O(2) in N(2)) or oxygen. In the vagally intact animals the peak value and duration of genioglossus muscle inspiratory activity increased in the first loaded breath before any noticeable change in the arterial blood gases. Hyperoxia decreased, whereas hypoxia increased the immediate response of the genioglossus activity to inspiratory loading. Removal of vagal volume-related feedback (by vagotomy) significantly increased the genioglossus muscle activity; the increase being more under hypoxia than under hyperoxia. In contrast to vagally intact animals, there was no first-breath increase in genioglossus activity during loading. The results indicate that the immediate involvement of the genioglossus muscle in response to inspiratory resistive load is mediated by vagal-volume feedback. Baseline oxygen tension before loading modulates the immediate reflex vagal-related response of the genioglossus muscle.

The purpose of the present study has been to determine whether pharyngeal dilator muscles participate in inspiratory load compensatory responses and if so, to elucidate role of upper airway mechanoreceptors in these responses. The experiments were performed on anaesthetized rabbits. Each animal was tested in three ways by the imposition of inspiratory resistive load: (1) at upper airways via face mask, (2) at the tracheostomic cannula placed below larynx (all upper airway receptors were 'bypassed') and (3) at the mouth after the section of the hypoglossus nerves (motor denervation of genioglossus muscle). The inspiratory load applied to the upper airways evoked significant increases in integrated genioglossus activity (to 129 +/- 14.7% of control) and its inspiratory duration (to 113 +/- 5% of control) already within the first loaded breath (P < 0.05). The increases in the inspiratory activity of musculius genioglossus were relatively greater than the simultaneous increases in the activity of the diaphragm. Motor denervation of the pharynx dilator muscles (including m. genioglossus) increased airway resistance to 184 +/- 19% of control (P < 0.05) and induced obstructive alterations in the breathing pattern during unloaded breathing: decrease in maximal inspiratory flow (-13%) and increase in the level of negative oesophageal pressure (+14%) and the peak diaphragm activity (+6%). After nervi hypoglossus sections additional increases in motor and pressure outputs were required in order to maintain unaltered ventilation at the same degree of loading as before denervation. The results indicate that the pharyngeal dilator muscles have a role in compensation of added inspiratory load. Activation of these muscles facilitate the load compensating function of 'pump' muscles by decreasing airway resistance. Tracheostomy did not reduce the genioglossus response to inspiratory loading, ruling out any role for upper airways receptors in the genioglossus response to inspiratory load compensations.

The present study was undertaken to test the hypothesis that recruitment of upper airway muscles in loaded breathing is a result of integration of peripheral chemoreceptor and pulmonary mechanoreceptor afferents. Experiments were performed in spontaneously breathing tracheostomized anesthetized rabbits. It had been studied the effects of inspiratory resistive loading to EMG activity of genioglossus muscle. In the intact rabbits the peak value and duration of inspiratory activity of genioglossus increased in loading. Imposition of resistive load in vagotomized animals did not evoke alteration in inspiratory activity of genioglossus in the first loaded breath. Hyperoxia decreased the response of genioglossus muscle to inspiratory loading and vagatomy. We conclude that hypoxic stimulation of peripheral chemoreceptors and decrease in volume-related afferent activity from pulmonary stretch receptors are major mechanisms of the upper airway muscle recruiment in inspiratory resistive loading.

The aim of this study was to map areas within the rat insular cortex from which respiratory responses originate and compare those sites with gastrointestinal control regions. The insular cortex was systematically microstimulated and histological location of responsive sites determined. Increased inspiratory airflow and decreased respiratory cycle duration were considered to be respiratory excitatory responses. The responses were localized in dysgranular and agranular insular cortex at levels caudal to the joining of the anterior commissure. More rostrally, respiratory inhibitory responses were elicited: these were manifested as a decrease in inspiratory airflow without a significant alteration in respiratory cycle duration. Respiratory inhibitory responses were usually accompanied by changes in gastric motility. These results suggest that the respiratory area in the rat insular cortex consist of two distinct zones which overlap a region modulating the gastrointestinal activity.

In anesthetised spontaneously breathing rabbits, an increase in the inspiratoryactivity m.genioglossus was greater than a simultaneous increase in the respiratory activity of the diaphragm cluring loaded breathing. A bypass of the air flow via tracheostoma did not affect the response of the m.genioglossus to a resistive load. The difference seems to be due to different functional inputs from the lung mechanoreceptors to phrenic and hypoglossal neuronal pools.

Two distinct patterns of respiratory responses to electrical microstimulation were elicited from the rat insular cortex: a decrease in respiratory airflow and tidal volume with no alteration of the respiratory rate (the inhibition response) and an increase in respiratory rate and inspiratory airflow (the excitation response). Gastric motility changes could also be elicited from the anterior insular cortex simultaneously with the inhibition response. The data suggests overlapping of the inhibition response area in the anterior insular cortex with a gastrointestinal representation there, and of the excitation response area in the posterior insular cortex with a cardiovascular representation.

The development of fatigue was investigated in the diaphragm of anaesthetized, tracheostomized, spontaneously breathing cats during restricted air flow. Ventilation, transdiaphragmatic pressure (Pdi), integrated electrical activity of diaphragm (Edi) and phrenic nerve (Eph) were measured simultaneously and expressed as a percentage of values at unloaded breathing. Inspiratory loads were 60, 70 and 80% of Pdi max. The Pdi max was measured by airway occlusion at functional residual capacity. The duration of loads was 40-60 min. The diaphragmatic fatigue developed only during heavy inspiratory loading (80% Pdi max). During the first 10 min of heavy load Pdi, Edi and Eph increased to 905 +/- 60%, 248 +/- 20% and 229 +/- 24%, respectively (P < 0.01), and then began to fall gradually. Ventilation declined to 39 +/- 3% after 60 min of heavy load (P < 0.01), resulting in acute hypercapnia and hypoxia. Initial fatigue appeared as a decrease in Pdi (to 781 +/- 63%) and parallel decline in Edi (to 233 +/- 21%) after 30 min of load (P < 0.05). Phrenic nerve activity did not change during this stage. These data suggest a peripheral basis of diaphragmatic fatigue, related to disorders in neuromuscular transmission. After 60 min of heavy load, Pdi fell to 675 +/- 49%, Edi declined to 209 +/- 28% and Eph decreased to 189 +/- 25%. We interpret the decrease in phrenic nerve activity as a weakening of central inspiratory drive and development of the central component of diaphragmatic fatigue in the last stage.

The inspiratory resistive load decreases the relative contribution of the diaphragm into formation of the respiratory volume, as has been show in anesthetised cats. The phenomenon can be due to both a sharp increase in the external intercostal muscles activity and to a fatigue of the diaphragmatic muscle in the inspiratory load. The contraphasic changes of these muscles' activity seem to be an adaptive response aiding to a more efficient overcoming of the resistance against breathing.

The experiments on anesthetized cats demonstrated that only a combination of hypoxia and inspiratory resistive loading induced respiratory arrest. The findings suggest that both central and peripheral mechanisms of apnea exist due to functional insufficiency of respiratory muscles as a result of synaptic disorder and excitatory contractility disorder in diaphragmatic muscle fibers.