Evaluation of energy metabolism and physical work capacity of divers for determining the optimal oxygen level during breathing gas mixture under pressure up to 5.1 MPa]

A complex evaluation of energy metabolism, oxygen-transport function of blood and physical work capacity of aquanauts has been performed during three imitation divings at depths of 400, 450 and 500 m in heliox as a breathing medium. These experiments have shown that optimal levels of partial oxygen pressure in artificial chamber environment are 30-33 kPa at 4.1 MPa, 32-35 kPa at 4.6 MPa and 33-34 kPa at 5.1 MPa. It is established that 24-days exposure of aquanautes to 4.6 MPa and 10-days exposure to 5.1 MPa yield no unfavourable changes of the examined organism functions. The activated lipid exchange in combination with stable carbohydrate catabolism, the elevated levels of oxygen consumption and its partial pressure in blood and transient fluctuations of erythropoiesis activity are interpreted as compensatory responses of diverse organisms under the influence of hyperbaric factors.     

Hemorheological Tests for Diagnosing the State of Venous Circulation

Hemorheological tests were used for diagnosing the state of venous circulation. Changes in the intravascular factors that determine increased blood viscosity in venous-blood insufficiency of the lower extremities were revealed by these methods. In males and females, these changes are similar but have different degrees of severity. The hemorheological shifts revealed impair the oxygen-transport capacity of the blood.     

The ventilatory responses of the caecilian Typhlonectes natans to hypoxia and hypercapnia

Typhlonectes natans empty their lungs in a single extended exhalation and subsequently fill their lungs by using a series of 10-20 inspiratory buccal oscillations. These animals always use this breathing pattern, which effectively separates inspiratory and expiratory airflows, unlike most urodele and anuran amphibians that may use one to many buccal oscillations for lung inflation and typically mix expired and inspired gases. Aquatic hypoxia had no significant effect on the breathing pattern or mechanics in these animals. Aerial hypoxia stimulated ventilatory frequency and increased the number of inspiratory oscillations but had little effect on inspiratory and expiratory tidal volume. Aquatic hypercapnia elicited a large significant increase in air-breathing frequency and minute ventilation compared to the small stimulation of minute ventilation seen during aerial hypercapnia. Some animals responded to aquatic hypercapnia with a series of three or four closely spaced breaths separated by long nonventilatory periods. Overall, T. natans showed little capacity to modulate expiratory or inspiratory tidal volumes and depended heavily on changing air-breathing frequency to meet hypoxic and hypercapnic challenges. These responses are different from those of anurans or urodeles studied to date, which modulate both the number of ventilatory oscillations in lung-inflation cycles and the degree of lung inflation when challenged with peripheral or central chemoreceptor stimulation.     

Compensatory reactions of the oxygen-transport systems of the body with hemic hypoxia (studies on a mathematical model]

The mathematical model suggested by the authors and results of experiments have been used to study the significance of basic oxygen-transport systems in regulation of oxygen conditions of the organism with acute and chronic hemic hypoxia of different seriousness, to determine a relative contribution of each of them to compensation of this hypoxic state, to estimate specific weight of proper "hypoxic" (induced by the effect on oxygen-transport blood function) and "toxic" (caused by the total toxic effect) action of sodium nitrite in the development of hemic hypoxia.     

Electron microscopic study of the tissue reaction of lungs exposed to quartz dust of varying dispersity

The tissue reaction of the lungs exposed to quartz dust of varying dispersity was studied by light, transmission and scanning electron microscopy. It is suggested that specific clinical manifestations of dust pathology are related to dispersity of silica. The largest quartz-containing dust particles give rise chiefly to the development of dust bronchitis. The most cytotoxic "medium" fractions lead to appearance of nodular forms of silicosis, whereas highly dispersed dust particles of quartz give rise to the development of diffusive sclerotic changes in the lungs.     

Role of airway nitric oxide on the regulation of pulmonary circulation by carbon dioxide.

The effects of hypercapnia (CO(2)) confined to either the alveolar space or the intravascular perfusate on exhaled nitric oxide (NO), perfusate NO metabolites (NOx), and pulmonary arterial pressure (Ppa) were examined during normoxia and progressive 20-min hypoxia in isolated blood- and buffer-perfused rabbit lungs. In blood-perfused lungs, when alveolar CO(2) concentration was increased from 0 to 12%, exhaled NO decreased, whereas Ppa increased. Increments of intravascular CO(2) levels increased Ppa without changes in exhaled NO. In buffer-perfused lungs, alveolar CO(2) increased Ppa with reductions in both exhaled NO from 93.8 to 61.7 (SE) nl/min (P < 0.01) and perfusate NOx from 4.8 to 1.8 nmol/min (P < 0.01). In contrast, intravascular CO(2) did not affect either exhaled NO or Ppa despite a tendency for perfusate NOx to decline. Progressive hypoxia elevated Ppa by 28% from baseline with a reduction in exhaled NO during normocapnia. Alveolar hypercapnia enhanced hypoxic Ppa response up to 50% with a further decline in exhaled NO. Hypercapnia did not alter the apparent K(m) for O(2), whereas it significantly decreased the V(max) from 66.7 to 55.6 nl/min. These results suggest that alveolar CO(2) inhibits epithelial NO synthase activity noncompetitively and that the suppressed NO production by hypercapnia augments hypoxic pulmonary vasoconstriction, resulting in improved ventilation-perfusion matching.     

Carotid chemoreceptors in ventilatory responses to changes in venous CO2 load

We examined the role of the carotid chemoreceptors in the ventilatory response to changes in venous CO2 load in 12 awake sheep using a venovenous extracorporeal perfusion circuit and two carbon dioxide membrane lungs (CDML). Three of the sheep had undergone surgical denervation of the carotid bodies (CBD). In the nine intact sheep, as CO2 was removed from or added to the peripheral venous blood through the CDML under normoxic conditions, there was a linear relationship between the rate of pulmonary CO2 excretion (VCO2) and the resulting rate of ventilation over a VCO2 range of 0--800% of control, so that arterial PCO2 remained close to isocapnic. In contrast, in the three CBD sheep, the ventilatory response to changes in VCO2 was significantly decreased under normoxic conditions, resulting in marked hypercapnia. The results indicate that the carotid chemoreceptors exert a major influence on the ventilatory response to changes in venous CO2 load.     

Gas-Exchange Properties of Salt-Stressed Olive (Olea europea L.) Leaves

The effects of two levels of salinity on photosynthetic properties of olive (Olea europea L.) leaves were observed either in low or in high H₂O vapor pressure deficit (vpd). Under moderate salt stress, stomata were found to be less open and responsive both to light and vpd, but the predominant limitation of photosynthesis was due to the mesophyll capacity of CO₂ fixation. We elaborate a procedure to correlate mesophyll capacity and liquid phase diffusive conductance. The estimated liquid phase diffusive conductance was reduced by salt and especially by high vpd; morphological and physiological changes could be responsible for this reduction. As a result, the chloroplast CO₂ partial pressure was found to decrease both under salt and vpd stress, thus resulting in a ribulose-1,5-bisphosphate carboxylase limitation of assimilation. However, under combined salt and vpd stress, O₂ sensitivity of assimilation increased, as would be expected under conditions of limiting ribulose 1,5-bisphosphate regeneration. Fluorescence induction measurements indicated that, under these conditions, energy supply may become limiting. When Cl⁻ concentration exceeded 80 millimolar in tissue water, zero growth and 50% leaf drop was observed. Fluorescence induction showed irreversible damage at Cl⁻ levels higher than 200 millimolar and basal leaves reached this concentration earlier than the apical ones.     

Chronic hypercapnia inhibits hypoxic pulmonary vascular remodeling

Chronic hypercapnia is commonly found in patients with severe hypoxic lung disease and is associated with a greater elevation of pulmonary arterial pressure than that due to hypoxia alone. We hypothesized that hypercapnia worsens hypoxic pulmonary hypertension by augmenting pulmonary vascular remodeling and hypoxic pulmonary vasoconstriction (HPV). Rats were exposed to chronic hypoxia [inspiratory O(2) fraction (FI(O(2))) = 0.10], chronic hypercapnia (inspiratory CO(2) fraction = 0.10), hypoxia-hypercapnia (FI(O(2)) = 0.10, inspiratory CO(2) fraction = 0.10), or room air. After 1 and 3 wk of exposure, muscularization of resistance blood vessels and hypoxia-induced hematocrit elevation were significantly inhibited in hypoxia-hypercapnia compared with hypoxia alone (P < 0.001, ANOVA). Right ventricular hypertrophy was reduced in hypoxia-hypercapnia compared with hypoxia at 3 wk (P < 0.001, ANOVA). In isolated, ventilated, blood-perfused lungs, basal pulmonary arterial pressure after 1 wk of exposure to hypoxia (20.1 +/- 1.8 mmHg) was significantly (P < 0.01, ANOVA) elevated compared with control conditions (12.1 +/- 0.1 mmHg) but was not altered in hypoxia-hypercapnia (13.5 +/- 0.9 mmHg) or hypercapnia (11.8 +/- 1.3 mmHg). HPV (FI(O(2)) = 0.03) was attenuated in hypoxia, hypoxia-hypercapnia, and hypercapnia compared with control (P < 0.05, ANOVA). Addition of N(omega)-nitro-L-arginine methyl ester (10(-4) M), which augmented HPV in control, hypoxia, and hypercapnia, significantly reduced HPV in hypoxia-hypercapnia. Chronic hypoxia caused impaired endothelium-dependent relaxation in isolated pulmonary arteries, but coexistent hypercapnia partially protected against this effect. These findings suggest that coexistent hypercapnia inhibits hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy, reduces HPV, and protects against hypoxia-induced impairment of endothelial function.     

Disturbances of Pulmonary Function in Mitral Valve Disease

To study the sequence of changes in respiratory function that occur in the natural history of mitral stenosis, and the physiological basis of “cardiac dyspnea”, 30 patients with chronic mitral valve disease were subjected to detailed pulmonary function tests. There was no significant change in vital capacity and functional residual capacity. The reduction in maximal mid-expiratory flow rate showed excellent correlation with the respiratory symptoms. The pulmonary capillary blood volume was increased in moderately advanced cases but was consistently reduced in the severest cases. Hyperventilation was due to an increased respiratory rate. Dyspnea was associated with increased respiratory work owing to the interrelation between the reduction in diffusion capacity, compliance, cardiac output, the increase in airway resistance, and the uneven ventilation and perfusion of the lungs. The amount of “effort” required to breathe is incommensurate with the external load in these patients.     

Effects of hypoxia and hypercapnia on surfactant protein expression proliferation and apoptosis in A549 alveolar epithelial cells

During lung injury alveolar epithelial cells are directly exposed to changes in PO(2) and PCO(2). Integrity of alveolar epithelial type II cells (AECII) is critical in lung injury but the effect of hypoxia and hypercapnia on AECII function, viability and proliferation has not been clearly investigated. Aim of the present work was to determine the direct effect of hypoxia and hypercapnia on surfactant protein expression, proliferation and apoptosis of lung epithelial cells in vitro. A549 alveolar epithelia cells were subjected to hypoxia (1%O(2)-5% CO(2)) or hypercapnia (21% O(2-) 15% CO(2)) and expression of surfactant protein C was measured and compared to normal conditions (21% O(2)- 5% CO(2)). Cell cycle progression and apoptosis were measured by flow cytometric analysis. RESULTS: A549 alveolar epithelial cells produce surfactant proteins, including surfactant protein C, when cultured under normal conditions, which is reduced under hypoxic conditions. Specifically, pro-SpC expression is moderately decreased after 8 h of culture in hypoxia, and is completely attenuated after 48 h. Hypercapnia decreases pro-SpC expression only after 48 h of exposure. Stimulation with TNF-alpha partly reverses pSPC decrease observed under hypoxic and hypercapnic conditions. Hypoxic culture of A549 cells results in progressive arrest of cells in the G1 phase of the cell cycle and increased apoptosis first observed 4 h following exposure and peaking at 24 h. In contrast hypercapnia has no significant effect on alveolar epithelial cell proliferation or apoptosis. CONCLUSIONS: Taken together we can conclude that hypoxia rapidly and severely affects AECII function and viability while hypercapnia has an inhibitory effect on pro-SpC production only after prolonged exposure.     

Influence of noradrenaline on the respiratory status of Rana balcanica red cell suspension under normoxia, hypoxia and hypercapnia: alpha 1-receptor involvement.

The effect of normoxia, hypoxia and hypercapnia on the extracellular pH, partial pressure carbon dioxide (pCO2), partial pressure oxygen (pO2) and HCO3- levels after noradrenaline treatment of Rana balcanica erythrocytes, was investigated. Noradrenaline caused a significant reduction of the extracellular pH which may have been due to the activation of red blood cell Na+/H+ exchange. Significant falls in the partial extracellular pressure of CO2 and O2 were evident. The initial reduction in extracellular pCO2 and pO2 was followed by a rise reflecting the desensitization of the Na+/H+ exchange after 15 min of hormone stimulation. Both hypercapnia and hypoxia increased the magnitude of these changes in relation to normoxia, although the greatest changes were observed under hypercapnic conditions. The involvement of alpha 1 receptors in regulating the concentration of respiratory gases after catecholamine stimulation was demonstrated. It is suggested that these responses increased the effectiveness of gas transfer over the respiratory surfaces.     

Effects of hypercapnia and NO synthase inhibition in sustained hypoxic pulmonary vasoconstriction

Background

Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined.

Method

We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate), and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min) and endothelial permeability.

Results

In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-N^G-Nitroarginine (L-NNA), a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS), decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc). This increase disappeared after administration of 1400 W.

Conclusion

Hypercapnia with and without acidosis increased HPV during conditions of sustained hypoxia. The increase of sustained HPV and endothelial permeability in hypoxic hypercapnia without acidosis was iNOS dependent.     

Transpiration rate and intercellular diffusive resistance in the tobacco leaf

The increase in the measured transpiration rate in tobacco leaves due to the experimentally decreased humidity of the bulk air was found to be significantly lower than the theoretical value calculated from the change of water vapour concentration gradients. Boundary layer and stomatal diffusive resistances remained unchanged under experimental conditions with no change of net photosynthetic CO₂ uptake. This suggests an increase in intercellular diffusive resistance with an increase in water vapour concentration gradient which is the driving force of water vapour diffusive part of transpiration flux. The increase can be ascribed to the lengthening of intercellular diffusive pathway as steeper water vapour concentration gradient in intercellular spaces results in an increased evaporating surface of intercellular cells thus moving the effective plane of vaporization in leaf mesophyll further inwards. Due to different and independent changes of concentration gradients for water vapour and CO₂, different length of intercellular diffusive pathways for CO₂ and water vapour may be expected.     

Functional Body Capacities under the Conditions of Various Concentrations of Carbon Dioxide and Oxygen

We determined a permissible ratio between carbon dioxide and oxygen concentrations during accidental situations. The experiments (n = 138, 10 h each) on the effect of various concentrations of carbon dioxide and oxygen in the inhaled air were conducted on male volunteers aged 20–40 years subjected to a special medical examination. All experiments were divided into five series: hypercapnia + normoxia, hypercapnia + hyperoxia, hypercapnia + hypoxia, normocapnia + hypoxia, and ambient air (control). The results showed that functional capacities of the body are less impaired under the conditions of hypercapnia combined with hyperoxia. Thus, in accidental situations associated with rapid accumulation of carbon dioxide in the atmosphere of airtight chambers, a synchronous increase in pO₂ to 220–230 torr can provide for the highest work capacity.     

Factors in the development of arterial hypoxemia in middle-aged and elderly people

Partial pressure of oxygen and carbon dioxide in alveolar air and arterial blood, lung diffusion capacity and its components, ventilation parameters, ventilation-perfusion ratio were determined in healthy people aged 60-89 (45 subjects) and aged 20-31 (19 subjects, controls). In elderly and old people PO2 in arterial blood was found to decrease with increasing alveolar-arterial PO2 gradient. In other words, arterial hypoxemia was determined by the disturbance in gas exchange between alveolar air and blood of lung capillaries. The diffusion capacity of lung decreased at the expense of membrane factor. Its age-related dynamics was mainly due to a decrease in the pulmonary diffusion surface occurring because of improper coordination of ventilation and perfusion in the lungs. The discrepancy of pulmonary ventilation and perfusion proved to be the leading factor of arterial hypoxemia in late ontogenesis.     

The in vitro Effect of a Magnetic Field on the Oxygen-Transport Function and the Gaseous Transmitter System in Blood

The effect of an alternating magnetic field with a magnetic flux density of 150 mT on the blood oxygen-transport function was studied. In vitro exposure of blood cells was performed following a 10-day series of in vivo exposure of the rat tail artery in combination with administration of chemical compounds that affect the formation of gaseous transmitters. In vitro exposure to a magnetic field changed the oxygen-transport function of the blood, as observed by a greater decrease in the affinity of hemoglobin for oxygen and an increase in the concentration of gaseous transmitters (nitric oxide and hydrogen sulfide). In animals to which nitroglycerin and sodium hydrosulfide were administered exposure to a magnetic field caused a shift in the oxyhemoglobin dissociation curve to the right; this effect was absent when a nonselective inhibitor of the NO synthase enzyme or an irreversible inhibitor of the cystathionine γ-lyase enzyme was added. These results suggest that the magnetic field affects the oxygen-binding properties of the blood by modifying intra-erythrocyte mechanisms that involve gaseous transmitters.     

Stress-Reactivity of Lungs according to Metabolic Function Parameters at Different Stages of Postnatal Ontogenesis

Analysis of parameters of metabolic function of lungs with respect to lipid metabolism was performed in rats under conditions of acute experimental emotional-nociceptive stress. Study of the stress-sensitivity of lungs in the comparative-age aspect has shown different extent of changes of several parameters of lipid metabolism in pulmonary tissue in animals of different age. The results of the study demonstrate areactivity and high stress-stability of lungs with respect to surface-active properties, free-radical processes, and lipase activity in early postnatal ontogenesis.     

Frequency-dependent effects of hypercapnia on respiratory mechanics of cats

The effect of increasing arterial partial pressure of CO2 (PaCO2) on respiratory mechanics was investigated in six anesthetized, paralyzed cats ventilated by constant-flow inflation. Respiratory mechanics were studied after end-inspiratory occlusions. Zero frequency resistance (Rmax), infinite frequency resistance (Rmin), and static elastance (Est) were calculated for the respiratory system, lung, and chest wall. Alveolar ventilation was manipulated by the addition of dead space to achieve a range of PaCO2 values of 29.3-87.3 mmHg. Cats did not become hypoxic during the experiment. Under control conditions marked frequency dependence in Rmax, Rmin, and Est of the respiratory system, lungs, and chest wall was demonstrated. The chest wall contributed 50% of the total resistance of the respiratory system. With increasing PaCO2 the only resistance observed to increase was Rmax of the lung (P less than 0.01). There were also no changes in the static elastic properties of either the lungs or the chest wall. These results suggest that hypercapnia increases resistance by changes in the lung periphery and not in the conducting airways.     

Myocardial oxygen supply during hypocapnia and hypercapnia in the dog

It has been postulated that a coronary vasoconstriction during hypocapnia might be opposed by a compensating coronary vasodilatation due to impaired myocardial oxygen supply. The present study was performed first to examine whether a maximal decline in coronary sinus (CS) oxygen content was reached during hypocapnia. During hypercapnia a myocardial "over perfusion" has been demonstrated. The second purpose of the present study was to examine whether a myocardial "over perfusion" is essential to maintain a sufficient myocardial tissue oxygen supply during hypercapnia. Closed-chest dogs were anesthetized with pentobarbital and hypocapnia was induced by hyperventilation. Nitrogen gas and carbon dioxide could both be added to the inspiratory gas to create arterial hypoxemia (arterial SO2 65%) and hypercapnia, respectively. Arterial hypoxemia during hypocapnia increased myocardial blood flow (MBF) by 50%, while CS SO2 decreased significantly. The decrease in CS SO2 demonstrates a reserve capacity of myocardial oxygen extraction during hypocapnia, thereby ruling out any major coronary vasoconstriction during hypocapnia. Hypercapnia during normoxemia increased MBF, myocardial oxygen delivery, and CS SO2 substantially, but this was not observed when hypercapnia was created during arterial hypoxemia. From the present results we conclude that hypocapnia does not cause any major coronary vasoconstriction, while hypercapnia results in a myocardial "over perfusion," which is a luxury perfusion not essential to maintain sufficient myocardial oxygen supply during hypercapnia.