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Modeling of chemical control of human respiratory system.

This paper addresses the fundamental understanding of the chemical control of respiratory system that would be needed to improve the efficiency of artificial ventilators and implement appropriate controllers. Hence, non-linear model for simulation of chemical control of human respiratory system under different physiological conditions is presented. The paper also presents the non-linear dissociation behaviors for oxygen and carbon dioxide solutions in the blood and the Bohr-Haldane effects as well as a new controller model. Tests were conducted on the model under different conditions such as hypoxia, hypercapnia, hypoventilation, and hyperventilation with some combination tests, in order to verify the validity of the assumptions that were made. Results indicate a very close agreement between the responses obtained from the present model and other published experimental and theoretical results. This model can be used to design a novel artificial respirator controller meeting the bodily requirements of the patient under mechanical ventilation.

Carbon Dioxide↗

The effects of dopamine on the respiratory system: friend or foe?

Dopamine (DA) is an immediate precursor of noradrenaline that has stimulatory or inhibitory effects on a variety of adrenergic receptors. DA is primarily used in the management of circulatory shock for its combined vasopressor and inotropic effects, but it may also exert significant effects on the respiratory system Although the respiratory effects of intravenous DA attract less attention than its hemodynamic effects, there is evidence that DA affects ventilation, pulmonary circulation, bronchial diameter, neuromodulation of sensory pulmonary nerves and lung water clearance. Through these complex mechanisms, DA may exert beneficial as well as detrimental effects on respiration. DA may have beneficial effects on the respiratory system by decreasing oedema formation and improving respiratory muscle function, but can also have deleterious effects, by inhibiting ventilation. Hence, DA may be beneficial in lung oedema, but harmful in cases of difficult weaning from mechanical ventilation. DA should be used with caution in patients with heart failure during weaning from mechanical respiration; however, critically ill patients with chronic obstructive pulmonary disease (COPD) do not show this negative effect of DA on ventilatory drive.

Animals↗

A pulse method of measuring respiratory system compliance in ventilated patients.

We describe a method of measuring total static respiratory system compliance (Crs) in ventilated patients during inflation, which appears to detect relaxation of respiratory muscles and does not require an end-inspiratory pause or disconnection of a constant-flow intermittent mandatory ventilation (IMV) circuit. Flow is measured with a pneumotachometer attached to the endotracheal tube. Transthoracic pressure is taken as the difference between mouth pressure measured at the proximal pneumotachometer port and body surface (atmospheric) pressure. Flow and transthoracic pressure are displayed on separate channels of a strip chart recorder. The ventilator is adjusted to deliver a constant rule of air flow. When inflation begins, the pressure tracing shows an initial step rise related to the flow resistance of the subject followed by a section with a slower rise and a constant slope. Respiratory system compliance is calculated by dividing the flow rate in L/sec by the slope of the pressure tracing in cm H2O/sec. Pulse Crs was compared with static Crs measured with an end-inspiratory pause in nine subjects receiving mechanical ventilation. Correlation between pulse Crs and static Crs in nine ventilated patients was highly significant (4 = .997, pulse Crs = 1.00 static Crs + 0.001). We conclude that with the pulse method, one can measure static Crs during inflation without an inspiratory pause and without disconnecting an IMV circuit.

Adult↗

The respiratory system during resuscitation: a review of the history, risk of infection during assisted ventilation, respiratory mechanics, and ventilation strategies for patients with an unprotected airway.

The fear of acquiring infectious diseases has resulted in reluctance among healthcare professionals and the lay public to perform mouth-to-mouth ventilation. However, the benefit of basic life support for a patient in cardiopulmonary or respiratory arrest greatly outweighs the risk for secondary infection in the rescuer or the patient. The distribution of ventilation volume between lungs and stomach in the unprotected airway depends on patient variables such as lower oesophageal sphincter pressure, airway resistance and respiratory system compliance, and the technique applied while performing basic or advanced airway support, such as head position, inflation flow rate and time, which determine upper airway pressure. The combination of these variables determines gas distribution between the lungs and the oesophagus and subsequently, the stomach. During bag-valve-mask ventilation of patients in respiratory or cardiac arrest with oxygen supplementation (> or = 40% oxygen), a tidal volume of 6-7 ml kg(-1) ( approximately 500 ml) given over 1-2 s until the chest rises is recommended. For bag-valve-mask ventilation with room-air, a tidal volume of 10 ml kg(-1) (700-1000 ml) in an adult given over 2 s until the chest rises clearly is recommended. During mouth-to-mouth ventilation, a breath over 2 s sufficient to make the chest rise clearly (a tidal volume of approximately 10 ml kg(-1) approximately 700-1000 ml in an adult) is recommended.

History, Ancient↗

Effects of abdominal opening on respiratory system mechanics in ventilated rats.

In 16 anesthetized paralyzed mechanically ventilated rats, respiratory system mechanics and rib cage dimensions were determined both before and after wide abdominal opening. In eight animals the end-inflation occlusion method disclosed statistically significant postoperative increases in respiratory system elastance (from 4.84 to 6.49 cmH2O.ml-1) and resistance (from 0.224 to 0.300 cmH2O.ml-1.s); the latter resulted from a rise of its uneven component (from 0.161 to 0.209 cmH2O.ml-1.s). In the remaining rats, rib cage morphometry at functional residual capacity after surgery showed significant decreases in lower rib cage circumference and anteroposterior and lateral diameters, whereas there was an increase in upper rib cage circumference and a fall in its lateral diameter. When these parameters were measured at end-inspiratory lung volume, the difference between intact and open abdomen were less striking; only lower rib cage circumference and upper rib cage lateral diameter significantly decreased postoperatively. Because surgery induced an expiratory volume of only 0.1 ml, it can be concluded that abdominal opening redistributed regional volumes within the lung, leading to increased unevenness in the system.

Abdomen↗

A cepstral method for analysis of acoustic transmission characteristics of respiratory system.

The generation and transmission process of transmitted sound signals (TSS) is analyzed and a mathematical model of TSS is established in this paper. The power cepstral characteristics of TSS are studied based on the mathematical model and a new analysis method of acoustic transmission of respiratory system using homomorphic processing technique is proposed. The experimental results show that the normal respiratory system has only one formant, while the abnormal respiratory system presenting lung consolidation has two formants and the second formant plays important role in that system. This new method is a simple and effective one.

Adult↗

Anchoring fibrils in the normal canine respiratory system.

Electron microscopic study of the normal canine respiratory tree disclosed the presence of anchoring fibrils, a distinct class of fibrils of extracellular connective tissue, in association with the following types of cells: (1) basal cells and special type cells of trachea and bronchi; (2) ciliated cells and basal cells of bronchioles; (3) ductal cells, secretory cells, and myoepithelial cells of tracheobronchial glands. Anchoring fibrils in the normal respiratory system measured up to 6,000 A in length and from 170 to 400 A in thickness, and had a banding pattern that differed from that of collagen fibrils and connective tissue microfibrils. They formed arcs, the ends of which inserted into the basal lamina underlying the basal portions of the cells, often in the vicinity of hemidesmosomes. Anchoring fibrils decreased in number and size in the more distal portions of the respiratory tree, and were not found in alveolar septums. Anchoring fibrils in lung appeared similar to those described in other organs, but were often small and inconspicuous. The function of these structures is to reinforce the attachment of the epithelial basal lamina to the underlying connective tissues.

Animals↗

Immunohistochemical study on the distribution of sodium-dependent vitamin C transporters in the respiratory system of adult rat.

As vitamin C (L-ascorbic acid, VC) is known to be essential for many enzymatic reactions, the study on the transport mechanism of VC through cytoplasmic membrane is crucial to understanding physiological role of VC in cells and the respiratory system. In this regard, the study on the newly identified sodium-dependent VC transporters (SVCTs), SVCT1 and SVCT2, is required in organs that contain high concentration of VC. We have shown the distribution of SVCT proteins in the respiratory system, which has been reported to be one of the organs with a high concentration of VC, using immunohistochemical techniques. In the present study, intense SVCT immunoreactivities (IRs) were mainly localized in the respiratory system epithelial cells. In the trachea, both SVCT1 and 2 were localized in the psuedostratified ciliated columnar epithelium. In the terminal bronchiole, SVCT1 and 2 IRs were mainly observed in the apical portion of the simple columnar epithelium. In addition, SVCT IRs was localized within the cell membrane of some alveolar cells, even though we could not identify the exact cell types. These results provide the first evidence that intense SVCT1 and 2 IRs were found in the apical portion of the respiratory epithelial cells, suggesting that SVCT proteins in the apical portion could transport the reduced form of VC included in the airway surface liquid into the respiratory epithelial cells.

Animals↗

Application of magnetic resonance (MR) imaging for the development and validation of computational fluid dynamic (CFD) models of the rat respiratory system.

Computational fluid dynamic (CFD) models of the respiratory system provide a quantitative basis for extrapolating the localized dose of inhaled materials and improving human health risk assessments based upon inhalation studies conducted in animals. Nevertheless, model development and validation have historically been tedious and time-consuming tasks. In recognition of this, we previously reported on the use of proton (1H) magnetic resonance (MR) imaging for visualizing nasal-sinus passages in the rat, and for speeding computational mesh generation. Here, the generation and refinement of meshes for rat nasal airways are described in more detail and simulated airflows are presented. To extend the CFD models to the complete respiratory tract, three-dimensional (3D) 1H MR imaging of rat pulmonary casts was also utilized to construct pulmonary airway meshes using procedures developed for the nasal airways. Furthermore, the feasibility of validating CFD predictions with MR was tested by imaging hyperpolarized 3He gas at physiological flow rates in a straight pipe with a diameter comparable to the rat trachea. Results from these diverse studies highlight the potential utility of MR imaging not only for speeding CFD development but also possibly for model validation.

Animals↗

Paralysis of ventilated newborn babies does not influence resistance of the total respiratory system.

Paralysis with pancuronium bromide is used in newborn infants to facilitate ventilatory support during respiratory failure. Changes in lung mechanics have been attributed to paralysis. The aim of this study was to examine whether or not paralysis per se has an influence on the passive respiratory mechanics, resistance (Rrs) and compliance (Crs) of the respiratory system in newborn infants. In 30 infants with acute respiratory failure, Rrs was measured during paralysis with pancuronium bromide and after stopping pancuronium bromide (group A). Rrs was also measured in an additional 10 ventilated infants in a reversed fashion (group B): Rrs was measured first in nonparalysed infants and then they were paralysed, mainly for diagnostic procedures, and the Rrs measurement repeated. As Rrs is highly dependent on lung volume, several parameters, that depend directly on lung volume were recorded: inspiratory oxygen fraction (FI,O2), arterial oxygen tension/alveolar oxygen tension (a/A) ratio and volume above functional residual capacity (FRC). In group A, the Rrs was not different during (0.236+/-0.09 cmH2O x s x mL(-1)) and after (0.237+/-0.07 cmH2O x s x mL(-1)) paralysis. Also, in group B, Rrs did not change (0.207+/-0.046 versus 0.221+/-0.046 cm x s x mL(-1) without versus with pancuronium bromide). FI,O2, a/A ratio and volume above FRC remained constant during paralysis. These data demonstrate that paralysis does not influence the resistance of the total respiratory system in ventilated term and preterm infants when measured at comparable lung volumes.

Acute Disease↗

Behaviour and aeration of the respiratory system in the domestic fowl embryo.

1. The monitoring of developmental stage and under-water dissection were used to examine the initial aeration of the respiratory system in domestic fowl embryos. 2. A virtually complete absence of free air within the chorioallantois was found before the beak had begun to make 'beak-clapping' movements, even when the membranes were already draped over its tip. 3. During the 'beak-clapping' stage, but before the membranes were pierced and before respiratory movements had begun, many embryos were found to contain free bubbles of air within the trachea and air sacs. 4. All embryos in which the respiratory system was aerated were found also to have froth in the crop or other parts of the digestive system. 5. Air was found in both the respiratory and digestive systems of all embryos examined after membrane penetration by the beak. 6. When air was injected into the chorioallantois before the stage of initial aeration it was recovered 5 min later from both the respiratory and digestive systems in under-water dissections. 7. It is suggested that lung ventilation takes place in the avian embryo in three distinct stages: the major air-ways become aerated, then respiratory movements begin and lastly the tertiary bronchi are slowly aerated. It is suggested also that movements involved in the imbibing of fluids play a part in aeration before the membranes are pierced.

Air↗

Respiratory outcome in preterm ventilated infants: importance of early respiratory system resistance.

UNLABELLED: Since severity of acute respiratory distress syndrome (RDS) has been decreasing, the aetiology of long-term respiratory problems may have changed in preterm infants. We investigated whether early neonatal respiratory resistance (Rrs) and compliance (Crs) were important determinants of respiratory morbidity and lung function abnormalities during the 1st year of life in ventilated preterm infants. In 70 infants of less than 37 weeks gestation, mechanically ventilated within 24 h after birth, Rrs and Crs were assessed daily during the first 3 days of life and medians were calculated subsequently (Rrsneo and Crsneo). Rrs and Crs were reassessed 1 year later in 57 of 70 infants (Rrs(1 year) and Crs(1 year)). After correction for endotracheal tube size, increased Rrsneo was significantly related to respiratory morbidity during the 1st year of life (OR 1.20, 95% CI 1.04 to 1.38; P = 0.013), increased Rrs(1 year) (multiplicative beta per kPa/l x s 1.017, 95% CI 1.000 to 1.034; P = 0.045), and decreased Crs(1 year) (multiplicative beta per kPa/l x s 0.986, 95% CI 0.974 to 0.998; P = 0.023). Associations were not adversely affected by degree of prematurity, neonatal disease and treatment. Crsneo did not show any significant associations. In the current surfactant era, increased Rrsneo, and not Crsneo was associated with poor respiratory outcome during the 1st year of life in preterm ventilated infants. Relationships were not adversely affected by measures reflecting degree of prematurity, neonatal disease, and ventilator conditions. CONCLUSION: our results indicate that inborn properties of the respiratory system have become increasingly important in relation to respiratory outcome instead of neonatal disease and treatment conditions.

Airway Resistance↗

Impedance of the lower respiratory system in ducks measured by forced oscillations during normal breathing.

The lower respiratory system of 10 conscious Pekin ducks breathing normally was subjected to superimposed oscillations of 1.3 to 16 Hz by a small volume piston pump. Induced sinusoidal flow (VO) and pressure (PO) signals were measured in late expiration, when the gas flow ventilated by the animal was minimum. The modulus of the respiratory impedance was calculated as the ratio PO/VO. The values obtained at the various oscillatory frequencies were compared to those predicted on the basis of a series mechanical network model consisting of resistive, inertial and compliant elements (RIC) using a least squares non linear regression method. The experimental data fitted well the frequency response of a simple RIC mathematical model. After correcting for the effects of the endotracheal tube, the mean values +/- SE of the optimized parameters were: resistance 4.8 +/- 0.4 cm H2O . L-1 . sec; inertance: 0.05 +/- 0.01 cm H2O . L-1 . sec2; compliance: 7.7 +/- 0.5 ml . cm H2O-1; natural frequency: 8.0 +/- 0.4 Hz. It is concluded that: (1) the lower respiratory system in ducks can be closely modeled by a RIC mechanical series network model; (2) the forced oscillation method can be used to investigate avian mechanics of breathing, with the birds awake and breathing spontaneously.

Airway Resistance↗

Optimization of the mammalian respiratory system: symmorphosis versus single species adaptation.

Taylor and Weibel's principle of symmorphosis hypothesized optimal design of the mammalian respiratory system, with no excess structure relative to its maximal O2 flux, VO2max. Although they found symmorphosis not to be a general principle of design, it might apply to a highly adapted aerobic athlete, e.g. the Thoroughbred racehorse. Using a mathematical model based on empirical data of the equine O2 transport system at normoxic VO2max, the fraction of the total limitation to O2 flux contributed by each of the respiratory transport steps is calculated as either the fractional change (F) in VO2max for a 1% change in each component, or as the fraction of total O2 pressure drop (R(int)) across each component at VO2max. When calculated as F, alveolar ventilation (VA) and pulmonary diffusing capacity (DLO2) are major limiting factors, circulatory convection (Q) is nearly as limiting, and peripheral tissue diffusing capacity (DTO2) is only one-third as important. When calculated as R(int), DLO2 is the major factor, VA and DTO2 contribute significantly, and Q is smallest. These patterns contrast with analogous studies in humans, in which Q is the single major limiting factor. The results suggest that strong selection for aerobic power in horses has maximized the malleable components of their respiratory systems until the least malleable structure, the lungs, has become a major limitation to O2 flux. Symmorphosis cannot determine if such a design is or is not optimized, as every system falls on a continuous distribution of relative optimization among species. However, the concept of symmorphosis is useful for establishing a framework within which a single species can be compared with a quantitatively defined hypothesis of optimal animal design, and compared with other species according to those criteria.

Adaptation, Biological↗

[Effects of chromium compounds on the respiratory system. 5. Long term inhalation of chromic acid mist in electroplating by C57BL female mice and recapitulation of our experimental studies].

Long term inhalation of CrO3 mist by C57BL mice The effects of the chromic acid mist used in electroplating on the respiratory system of C57BL mice (female; n = 43) were examined histopathologically after exposure for 12 months to the mist (1.81 mgCr/m3-120 min, twice a week). Among the 23 mice sacrificed at 12 months after the first exposure, three cases of perforation in the nasal septs, a case of proliferative change of the tracheal epithelium, nine cases of emphysema and four of adenomatous metaplasia of the lungs were observed on antopsy. Among the 20 mice which were sacrificed six months after the last exposure, the same changes as the 12-month exposure group were also observed in the nasal septum, trachea and lungs, but papillomas observed in the nasal epithelia of six mice and adenoma in the lung of a mouse were new findings not seen in the 12-month exposure group. These results suggest that, in view of the low incidence of spontaneous lung tumor in C57BL mice, inhalation of chromic acid mist in electroplating might be a risk factor of lung cancer. Additionally, the occurrence of papillomas in the nasal epithelium demonstrates the need of directing attention to the possible development of cancer of the upper respiratory tract in chromium electroplating workers. Recapitulation on our experimental studies Upon completion of our five reports on the effects of chromium compounds on the respiratory system, a recapitulation of our experimental studies was made and compared with the findings of a number of reports on chromium. It was experimentally and epidemiologically confirmed that hexavalent chromium compounds act as carcinogens and cause specific biological effects on the respiratory system. These characteristics of hexavalent compounds might be attributable to the strong oxidizing potency and/or high permeability through the cell membrane. Furthermore, hexavalent compounds might be entirely different in biological action from trivalent compounds which are chemically most stable.

Aerosols↗

Contribution of impedance measurement of the respiratory system to bronchial challenge tests.

The contribution of impedance measurement of the respiratory system to bronchial challenge tests was studied in 64 asthmatics and 23 control subjects. After histamine challenge, resistance values increased significantly at all frequencies but most markedly at the lower frequencies in the asthmatic group; reactance values significantly decreased at all frequencies. In the control group, resistance significantly increased at 8 and 12 Hz. However, reactance decreased significantly at all frequencies. By multiple logistic model analysis, a simple discriminant score was found with great discriminating power to differentiate asthmatics and nonasthmatics. The discriminating score equals 9 X FEV1 aft - 7 X FEV1 bef. Adding the forced oscillation technique to the equipment for measuring the bronchial response after challenging procedures can give information about the localization of the response to the challenge in the respiratory system.

Adult↗

The respiratory system and diazotrophic activity of Acetobacter diazotrophicus PAL5.

The characteristics of the respiratory system of Acetobacter diazotrophicus PAL5 were investigated. Increasing aeration (from 0.5 to 4.0 liters of air min(-1) liter of medium(-1)) had a strong positive effect on growth and on the diazotrophic activity of cultures. Cells obtained from well-aerated and diazotrophically active cultures possessed a highly active, membrane-bound electron transport system with dehydrogenases for NADH, glucose, and acetaldehyde as the main electron donors. Ethanol, succinate, and gluconate were also oxidized but to only a minor extent. Terminal cytochrome c oxidase-type activity was poor as measured by reduced N, N,N,N'-tetramethyl-p-phenylenediamine, but quinol oxidase-type activity, as measured by 2,3,5,6-tetrachloro-1,4-benzenediol, was high. Spectral and high-pressure liquid chromatography analysis of membranes revealed the presence of cytochrome ba as a putative oxidase in cells obtained from diazotrophically active cultures. Cells were also rich in c-type cytochromes; four bands of high molecular mass (i.e., 67, 56, 52, and 45 kDa) were revealed by a peroxidase activity stain in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. KCN inhibition curves of respiratory oxidase activities were biphasic, with a highly resistant component. Treatment of membranes with 0.2% Triton X-100 solubilized c-type cytochromes and resulted in a preparation that was significantly more sensitive to cyanide. Repression of diazotrophic activity in well-aerated cultures by 40 mM (NH(4))(2)SO(4) caused a significant decrease of the respiratory activities. It is noteworthy that the levels of glucose dehydrogenase and putative oxidase ba decreased 6. 8- and 10-fold, respectively. In these cells, a bd-type cytochrome seems to be the major terminal oxidase. Thus, it would seem that glucose dehydrogenase and cytochrome ba are key components of the respiratory system of A. diazotrophicus during aerobic diazotrophy.

Acetobacter↗

Idiopathic scoliosis. Mechanical properties of the respiratory system and the ventilatory response to carbon dioxide.

The aims were to examine the effects of scoliosis (angle), and age on lung volumes, elastic properties of the respiratory system, and the ventilatory response to CO2. The mean age of the 55 patients was 25.4 plus or minus SEM 2.5 yr, and the mean angle was 80 plus or minus SEM 4.2. The mean plus or minus SEM percent predicted lung volumes were vital capacity (VC), 60.5 plus or minus 2.7; total lung capacity (TLC), 70,2 plus or minus 2.6; functional residual capacity (frc), 79.3 plus or minus 3.2; and residual volume (RV), 99.7 plus or minus 5.2. The correlation coefficients between the angle of scoliosis and each of the following were significant: TLC (-0.548), percent predicted TLC (-0.547), VC (-0.485), percent predicted VC (-0.523), FRC (-0.533), percent predicted FRC (-0.338), RV (-0.438), and percent predicted RV (-0.318). The mean compliance of the total respiratory system (Crs) was 0.049 litter/cm H2O plus or minus SEM 0.004, and the mean compliance of the chest wall (Ccw) was 0.080 liter/cm H2O plus or minus SEM 0.012. The Crs and Ccw were inversely proportional to the angle (r-0.620 and -0.721) and directly proportional to the height and the weight. The mean deltaV/deltaPco2 was 1.32 liter/min per mm Hg (SEM 0.171), and the mean deltaVt/deltaPco2 was 28.9 ml/mm Hg (SEM 3.64). The correlation coefficients between deltaV/deltaPco2 and the following were height, 0.499; VC, 0.792; TLC, 0.632; AND Crs, 0.520; and between the deltaTt/deltaPco2 and the following were height, 0.500; VC, 0.878; TLC, 0.802; and Crs, 0.590. We conclude that body size and the deformity were the determinants of the lung volumes and the mechanical properties of the respiratory system, and that these variables were the major factors in both the magnitude and pattern of the ventilatory response to CO2. The correlations between age and the mechanical properties of the respiratory sytem, deltaV/deltaPco2, and deltaVt/deltaPco2, were not significant, but the correlation coefficients between age and several of the derivatives of deltaV/deltaPco2 and deltaVt/deltaPco2 were significant.

Adolescent↗