Causes of Hypoxemia in COVID-19.

The global pandemic of a new coronavirus disease (COVID-19) has posed challenges to public health specialists around the world associated with diagnosis, intensive study of epidemiological and clinical features of the coronavirus infection, development of preventive approaches, therapeutic strategies and rehabilitation measures. However, despite the successes achieved in the study of COVID-19 pathogenesis, many aspects that aggravate the severity of the disease and cause high mortality of patients remain unclear. The main clinical manifestation of the new variant of SARS-CoV-2 virus infection is pneumonia with massive parenchymal lesions of lung tissue, diffuse alveolar damage, thrombotic manifestations, disruption of ventilation-perfusion relationships, etc.

A Comparative Assessment of Effects of Major Mediators of Acute Phase Response (IL-1, TNF-α, IL-6) on Breathing Pattern and Survival Rate in Rats with Acute Progressive Hypoxia.

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.

[EFFECTS OF PROINFLAMMATORY CYTOKINE INTERLEUKIN-1P ON RESISTANCE TO ACUTE HYPOXIA].

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.

[ASSOCIATED RESPIRATORY AND HEMODYNAMICS RESPONSE TO ACUTE NORMOBARIC PROGRESSIVE HYPOXIA IN ANESTHETIZED RATS].

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.

The Mechanisms of Compensatory Responses of the Respiratory System to Simulated Central Hypervolemia in Normal Subjects.

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.

Effects of inspiratory muscle training on resistance to fatigue of respiratory muscles during exhaustive exercise.

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.

Intersystem relationships of respiration and hemodynamics in the initial period of postural effects.

We studied the dependence of parameters of lung volumes and the elastic properties of the lungs on changes in the central hemodynamics occurring in the initial period of passive postural changes in cats. It was found that transition from the horizontal to head-up and head-down tilting was accompanied by opposite hemodynamic changes in the cranial and caudal parts of the body. Changes in lung compliance and functional residual capacity of the lungs were opposite and linearly depended on the intensity of hemodynamic shifts, which indicates passive character of the primary disorders primarily determined by a physical factor, gravity-dependent redistribution of body fluids.

EMG analysis of human inspiratory muscle resistance to fatigue during exercise.

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.

[Intersystem interaction of the respiration and blood circulation].

The review includes modern data about the functional interaction of respiratory and bloods circulatory systems in different conditions. The special attention is given to adaptive changes of respiratory and haemodynamic indices in extreme conditions. Based on the own researches physiological parallels between intersystem correlation of respiratory biomechanics and haemodynamics in the conditions of normal gravitation and weightlessness are drawn.

[Ventilatory response to hypercapnia during head-down tilt].

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.

Effects of body position on the ventilatory response to hypercapnia.

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 P(ET)CO(2)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.

[The ventilatory response to isocapnic hypoxia during head-down tilt].

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.

Effects of intermittent hypoxic training on orthostatic reactions of the cardiorespiratory system.

The possibility of using intermittent hypoxic training for stimulation of physiological mechanisms underlying the compensatory hemodynamic reactions to orthostatic load was studied in animal experiments. Intermittent hypoxic training had a favorable impact on circulatory reactions, which manifested in stabilization of blood pressure and heart filling pressure and in a decrease in orthostatic hypotension during the initial period of orthostasis. We hypothesized that the positive effect of intermittent hypoxic training on the correction of negative hemodynamic shifts is determined by the training effect aimed at the increase in the vascular tone and venous return to the heart.

[The role of lung afferent system in respiratory control during head-down tilt].

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.

[Cardiorespiratory responses of animals to passive orthostasis after intermittent hypoxia during head-down tilt].

Cardiorespiratory responses induced by upright tilt before and after intermittent hypoxia during head-down tilt, were investigated in rabbits. Arterial blood pressure, heart rate, central venous pressure, transmural filling pressure of the heart (calculated as the product of esophageal and central venous pressure), breathing frequency, esophageal pressure were measured in supine (baseline), head-down and upright posture. Our results indicate a reduction in orthostatic responses in cardiovascular system after intermittent hypoxia.

[The dynamic of breathing biomechanics and intrathoracic hemodynamics parameters during microgravity modeling].

In ground-based model of the hemodynamics effects of weightlessness, the intersystem relation of breathing and circulation was investigated during inspiration and expiration separately in anesthetized catz. It's shown that the dynamics of central venous pressure, esophageal pressure and filling pressure of the heart during inspiration in supine and head-down tilt position has obvious similarity to those which hypothetically can be present in microgravity. The results suggest that intrathoracic hemodynamics during inspiration in supine and head-down position may be an adequate ground model for investigation of weightlessness influences on intrathoracic circulation.

Influence of changes in intrathoracic and central venous pressure on cardiac filling dynamics.

Changes in the ratio between intrathoracic and central venous pressure were studied in narcotized cats under conditions of constant positive or negative pressure ventilation. Transformation of elastic characteristics in the respiratory system caused by changes in intrathoracic pressure led to inversion of the ratio between transpulmonary intrathoracic and central venous pressure determining right atrial filling pressure.

[Respiration and cardiovascular mechanisms of hypobaric correction of the head-down redistribution of local blood volumes].

The focus was placed on the physiological mechanisms of correction of the blood redistribution during the head-down tilt (HDT) with a discrete or complex use of the methods of negative pressure respiration (NPR) and lower body negative pressure (LBNP). It was evidenced that rise in the intracranial hydrostatic pressure in HDT (-6 degrees) can be compensated by NPR within a range of -10 to -15 cm of water column causing decrease in the intrasternal pressure from -5.04 to -7.

[Transmural pressure in the right atrium during positive pressure respiration in cats].

The influence of continuous positive pressure breathing (cm H2O) on the breathing mechanics, central venous pressure, and transmural pressure in the right atrium, were studied in anaesthetised cats separately during inspiration and expiration. It's shown that hemodynamics effects are directly connected with the influence of increased intrathoracic pressure during whole breathing cycles in contrast with the phase changes in natural expiration and inspiration. The inversion of relation of intrathoracic and central venous pressure due to displacement of the mechanical respiratory characteristics became the factors defining the fall of the right atrium filling pressure.

[Influence of breathing at negative pressure on redistribution of local blood volumes in anti-orthostatic load in cats].

To improve methods of offsetting the hemodynamic shifts in microgravity, applicability of breathing at negative pressure (BNP, pressure relief by -5.0 cm of water column) during inspiration and expiration was assessed in acute experiments with unconscious cats tilted head-down (-30 degrees). Direct measurement of pressure in v.

[The effect of complex barometric exposure on hemodynamics during simulation of the physiological impacts microgravity in animals].

In experiments with anesthetized cats effects of breathing under negative pressure (BNP, -5 cm of water column) combined with lower body negative pressure (LBNP, -20 cm of water column) on the cardiorespiratory reactions to postural simulation of the hemodynamic shifts in microgravity were studied. Evidence was obtained that this complex barometric exposure of tilted animals (-30 degrees) imitated the central and peripheral hemodynamics characteristic of tilt at the calculated inclination of +6 degrees up to +12 degrees. Extrapolation of the experimental data on the orthodox physiological model of microgravity (HDT, -6 degrees) allows an assumption that the protocol of complex barometric exposure tested in this experiment transforms the hemodynamic parameters under study to the levels close to those in the vertical body.

[Effect of the body antiorthostatic posture on various circulation and respiration parameters in anesthetised cats].

In anaesthetised cats, antiorthostatic posture of the body with an inclination angle of 30 degrees increased pressure in the vena cava superior and in jugular vein. The rest of the cardio-respiratory parameters were changed insignificantly. Physical and physiological mechanisms of the blood regional redistribution in alteration of the body gravitation orientation, are discussed.