Structural aspects of gas exchange

The lung is composed of several million small air spaces, lined by a delicate tissue membrane separating air from capillary blood. The design features of the gas exchange region in the lung are optimal for gaseous diffusion, by having a very extensive contact surface but with a minimal tissue barrier composed of an epithelial and endothelial layer separating an interstitial layer. The extent of the gas exchange surface in adult lungs is determined by general maturation which in turn is influenced by metabolic requirements of the organism. Environmental factors can modulate the pattern of ultimate lung development. Lung inflation causes air spaces to expand mainly by a process of tissue unfolding beneath an extremely thin layer of alveolar surfactant. This ensures cellular integrity during extreme deformations while at the same time providing a reserve of gas exchange surface so that functional diffusion capacity at all lung volumes is less than the structural maximum.     

Structural and functional organization of the respiratory center

The main experimental data on the organization of the respiratory center accumulated during the past 200 years are summarized. It is emphasized that the existence of separate, reciprocally interrelated, inspiratory and expiratory centers has never been proved. The notion of multiple respiratory centers in the CNS, including pneumotaxic, apneustic, gasping, and deep-exhalation centers, which allegedly underlie the multiple forms of respiratory movements, is demonstrated to be unjustified. Upon systemic consideration, the evidence in favor of the decisive role of neurons of the pre-Bötzinger complex and preinspiratory neurons in initiating the respiratory rhythm and maintaining rhythm generation in the respiratory center is contradictory and unconvincing. It is assumed that the respiratory center located in the medullary region of the brain of intact animals and humans fulfills the main functions of endogenous self-sustained generation of the respiratory rhythm, chemoregulation, and mechanoregulation in the respiratory system in an integrated manner, according to the general requirements of the body at a given moment.     

The variability of respiratory pattern and gas exchange

It is known, that spectral analysis of heart rate and respiratory variability allows to find out the very low frequency (VLF) rhythm. However it is not known, it is necessary to carry this rhythm to what type of wave processes. The purpose of the present researches was to study the respiratory variability and the variability of gas exchange parameters. 10 healthy subjects have been surveyed. The pneumogramms within 30 minutes spent record, and then a method "breath-by-breath" within 30 minutes registered gas exchange parameters (Ve--lung ventilation, V(O2) -O2 consumption and other parameters). Fast Fourier transform method has found out two groups of the basic peaks. The first--in a range 0.2-0.3 Hz (a time cycle--3-5 s), that corresponds respiratory frequency which size at subjects varied from 12 to 20 per minute. The second--in a range 0.002-0.0075 Hz, that corresponds VLF diapason (a time cycle--1-3.5 minutes). At the analysis pneumogramms rhythms in the same ranges have been established. The carried out researches allow to draw a conclusion on steady character of wave process in a VLF-range. It can be carried to quasi-periodic oscillations type. First oscillator or respiratory frequency it is formed by means of mechanisms of chemoreception. Considering, that V(O2) and V(CO2) are function energy exchange, it is possible to believe, what exactly energy demand define the second oscillator.     

The variability of pulmonary gas exchange and respiratory pattern

Very-low-frequency (VLF) fluctuations, whose nature is probably determined by rhythms of energy processes, are known to determine the variability of respiratory and heart rates. It is still unclear to which type of wave processes (chaotic or regular) these rhythm patterns belong. The goal of this study was to investigate the rhythms of pulmonary gas exchange and the variability of the respiratory pattern, as well as to find their possible relation. To analyze the variability of ventilation indices in the VLF band, pneumograms were recorded for 30 min and then the pulmonary gas exchange indices (Ve, pulmonary ventilation; V_O2 V_{O_2 }, oxygen consumption; V_CO2 V_{CO_2 }, carbon dioxide release) were recorded for 30 min using the breath-by-breath method in ten healthy subjects. Spectral analysis carried out using the fast Fourier transform revealed two groups of major peaks: the first one was in the range from 0.2 to 0.3 Hz (the time interval of 3–5 s), which was in good agreement with the respiratory rate varied from 12 to 20 per min in tested subjects; the second was from 0.002 to 0.0075 Hz, which corresponded to the VLF band. The data make it possible to draw a conclusion about the stability of the wave processes found. Apparently, the slow-wave pattern of the pulmonary gas exchange indices belongs to the quasi-periodic oscillation type, reflecting synchronization of oscillators with incommensurable frequencies when the two-frequency pattern dominates. The first oscillator is the chemoreceptor mechanism of the regulation of ventilation, the nature of the second one is still unclear. Taking into consideration that V_O2 V_{O_2 } and V_CO2 V_{CO_2 } depend on energy demand, one can suppose that energy processes form (an)other oscillator(s) of periodic processes.     

The development of sympathetic innervation and the functional state of the cardiovascular system in newborn dogs.

The present study in dogs indicates that the peripheral sympathetic fibers develop mostly after birth and reach a full maturity at about 2 months of life. The norepinephrine content of the heart, spleen, intestine, salivary glands, and adrenal glands increased from birth to 56 days of age. In contrast, the content of the stellate ganglia decreased during this period. In most of the organs studied, the uptake of [3H] norepinephrine developed in parallel with the norepinephrine content, except in the right atrium and salivary glands where it was fully developed soon after birth. During development, the systemic blood pressure increased from 40 to 100 mm Hg. Bilateral adrenal vessel clamping failed to induce a fall in blood pressure in growing dogs which indicates that the adrenal medulla or the baroreceptors did not fully compensate for the lack of peripheral sympathetic fibers and for the lower blood pressure in newborn animals. Although cardiac norepinephrine content was still very low in 10-day-old animals, cardiovascular responses to direct and reflex sympathetic stimulation were similar to those observed in 56-day-old animals. These results indicate that the sympathetic nervous system becomes functional before the fibers reach their full maturity.     

Measurement of respiratory gas exchange during artificial respiration

This paper reports a new system for the continuous measurements of respiratory gas exchange in ventilated subjects. It involves mixing some of the inspired gas with all of the expired gas and withdrawing the mixture at a constant rate through a dry gas meter that measures the flow. The inspired gas and expired gas mixtures are sampled and O2 and CO2 concentrations measured with a paramagnetic gas analyzer and a capnograph, respectively, to an accuracy of 0.01%. Evidence is presented to confirm the necessary stability and sensitivity of these instruments. It is possible to use the system with high inspired O2 concentrations, with ventilators where there is incomplete separation of inspired and expired gas, and in the presence of intermittent mandatory ventilation, positive end-expiratory pressure, and continuous airway pressure. The system was compared with the N2-dilution method and with the collection of expired gas in a Douglas bag in dog experiments and with patients in the intensive therapy unit. Excellent correlation between these methods was found in all circumstances.     

Oxygen-sensing pathways and the development of mammalian gas exchange

Oxygen-sensing pathways have been extensively explored in the context of homeostatic responses to hypoxic episodes; however, little is known of their involvement in the morphogenesis of respiratory structures (mitochondria, placenta, lung) during development in utero. This review identifies four essential loci where oxygen signalling pathways may cue the development of respiratory structures as: (i). mitochondrial biogenesis coupled with muted oxidative function dependent on the hypoxia-sustained production of NO; (ii). the generation of oxygen gradients which drive trophoblast differentiation and the formation of the chorionic gas exchange interface of the placenta; (iii). the proliferation and epithelial/endothelial differentiation of mesenchyme during the initiation of lung morphogenesis; and (iv). the regulation of epithelial fluid secretion/absorption in the lung. The identification of these oxygen-regulated developmental stages clarifies the close association between oxygen availability, reactive oxygen species and the morphogenesis of gas exchange structures and bears with it the implication that these pathways set the scope for aerobic metabolic performance throughout life.     

Structural and functional organization of Complex I in the mitochondrial respiratory chain

Metabolic flux control analysis of NADH oxidation in bovine heart submitochondrial particles revealed high flux control coefficients for both Complex I and Complex III, suggesting that the two enzymes are functionally associated as a single enzyme, with channelling of the common substrate, Coenzyme Q. This is in contrast with the more accepted view of a mobile diffusable Coenzyme Q pool between these enzymes. Dilution with phospholipids of a mitochondrial fraction enriched in Complexes I and III, with consequent increased theoretical distance between complexes, determines adherence to pool behavior for Coenzyme Q, but only at dilution higher than 1:5 (protein:phospholipids), whereas, at lower phospholipid content, the turnover of NADH cytochrome c reductase is higher than expected by the pool equation.     

Delayed kinetics of respiratory gas exchange in the transition from prior exercise

The kinetics of oxygen uptake (VO2), carbon dioxide output (VCO2), and expired ventilation (VE) in the transition from rest or from prior exercise were studied in response to step increases in power output (PO). The data were modeled with a single-component exponential function incorporating a time delay (TD). Each subject exercised on four occasions. Test 1 was an incremental test for determination of ventilatory anaerobic threshold (AT). Step increase tests were rest to 80% of PO at AT (test 2), rest-40% AT (3a), 40-80% AT (3b), rest-40% AT (4a), and 40-120% AT (4b). Respiratory gas exchange was monitored by open-circuit techniques. The VO2 kinetics showed the time constant (tau) to be longer in the transitions from prior exercise [tests 3b and 4b were 60.6 +/- 10.8 (SD) and 79.2 +/- 17.4 s] than from rest (tests 2, 3a, and 4a were 37.8 +/- 7.2, 30.0 +/- 7.8, and 39.6 +/- 17.4 s). The mean response time (MRT = tau + TD) was also longer for these tests. Kinetic analysis for VCO2 showed a tendency for tau to be shorter for the tests from prior exercise, but neither tau nor tau + TD were significantly different between tests. In contrast to VCO2, VE kinetics showed a significantly longer tau + TD for test 3b (P less than 0.05) and test 4b (P less than 0.01). This study has shown the VO2 kinetics to be delayed when a given increment in PO occurred from prior exercise, whether the final PO was below or above the AT. Further, the dissociation of VCO2 and VE kinetics does not support a direct link between these two variables as the sole control factor in exercise hyperpnea.     

Structural and functional units in the pial microvascular system

A study was made of the pial arterial microcircles formed upon successive branching and anastomosing of the terminal pial vessels on the brain cortex surface at different levels of the phylogenetic development of the vertebrata. It was discovered that the pial arterial microcircles progressively become more complicated in the following order: chicken, rabbit, cat, dog, monkey. The morphological signs of the microcircles undergo progressive development: 1) they are formed primarily from small pial arterial branches possessing high vasomotor activity; 2) the area of each circle becomes less and less and their amount per unit of the brain surface increases respectively; 3) the quantity of the feeding arterial branches rises despite the reduction of the circle size; 4) the number of outgoing precortical and radial arteries entering the brain cortex increases; 5) the areas of the brain cortex supplied by individual radial arteries become less and less. This ensures increasingly delicate regulation of adequate blood supply of the smallest areas of the brain cortex.