Bellows-less lung system for the human patient simulator

A new bellows-less lung simulator utilising a fixed-volume pressure controller to simulate spontaneous breathing is presented as an alternative to the traditional bellows-driven mechanical lung system in the human patient simulator (HPS). The HPS is a fully interactive, life-like simulator used to train medical students and anaesthesia residents. The lung simulator simulates carinal pressure, which allows for simulation of actively breathing or ventilated patients. In the current HPS implementation, breathing is physically simulated with a pair of bellows and a computer-controlled piston, but, owing to physical and dynamic constraints, the model suffers from a lot of dead space. Furthermore, the set-up incorporates several mechanical components that require time-consuming calibrations, which drives up manufacturing costs. A bellows-less lung simulator has been designed and built which successfully simulates airflow in and out of the mouth by controlling the carina pressure. The new system is able to simulate tidal volumes between 400 and 500 ml, with flow rates of 4.3–5.7l min⁻¹ at a respiratory rate of 12 breaths per minute. The new design not only matches the ventilation performance of the HPS, but also simulates at 60 breaths per minute, which the HPS cannot maintain.     

Effect of compliant intermediate airways on total respiratory resistance and elastance in mechanical ventilation.

Total respiratory resistance and elastance were estimated off-line in a sample of 60 patients undergoing mechanical ventilation by means of two regression models in order to analyse and understand a possible physiological mechanism determining differences in inspiration and expiration. The first model considered a single value for resistance and elastance over a whole breathing cycle, whereas the second model considered separate values for inspiratory and expiratory resistance and a single value for elastance. Inspiratory resistance was found to be lower than expiratory resistance, and intermediate values were obtained for resistance estimated over the whole breathing cycle. Student's t-test showed a highly significant difference between these resistance estimates, and principal components analysis demonstrated a significant increase in information when both inspiratory and expiratory resistances were used. Minor differences were found between values of elastance calculated with the two approaches. In an attempt to interpret these experimental results, a lung model incorporating the non-linear viscoelastic properties of the intermediate airways was considered. This model suggested that changes in intermediate airway volume play a significant role in breathing mechanics during artificial ventilation and indicated that inspiratory and expiratory resistance could be useful parameters for locating airway obstruction.     

A new infant hybrid respiratory simulator: preliminary evaluation based on clinical data

A new hybrid (numerical–physical) simulator of the respiratory system, designed to simulate spontaneous and artificial/assisted ventilation of preterm and full-term infants underwent preliminary evaluation. A numerical, seven-compartmental model of the respiratory system mechanics allows the operator to simulate global and peripheral obstruction and restriction of the lungs. The physical part of the simulator is a piston-based construction of impedance transformer. LabVIEW real-time software coordinates the work of both parts of the simulator and its interaction with a ventilator. Using clinical data, five groups of “artificial infants” were examined: healthy full-term infants, very low-birth-weight preterm infants successfully (VLBW) and unsuccessfully extubated (VLBWun) and extremely low-birth-weight preterm infants without (ELBW) and with bronchopulmonary dysplasia (ELBW_BPD). Pressure-controlled ventilation was simulated to measure peak inspiratory pressure, mean airway pressure, total (patient + endotracheal tube) airway resistance (R), total dynamic compliance of the respiratory system (C), and total work of breathing by the ventilator (WOB). The differences between simulation and clinical parameters were not significant. High correlation coefficients between both types of data were obtained for R, C, and WOB (γ _R  = 0.99, P < 0.0005; γ _C  = 0.85, P < 0.005; γ_WOB = 0.96, P < 0.05, respectively). Thus, the simulator accurately reproduces infant respiratory system mechanics.     

Respiratory mechanics and lung tissue remodeling in a hepatopulmonary syndrome rat model

Intrapulmonary vasodilation is a hallmark of the hepatopulmonary syndrome (HPS). However, its effects on respiratory mechanical properties and lung morphology are unknown. To determine these effects, 28 rats were randomly divided to control and experimental HPS groups (eHPS). The spontaneous breathing pattern, gas exchange, respiratory system mechanical properties, and lung and liver morphology of the rats were evaluated. Tidal volume, minute ventilation and mean inspiratory flow were significantly reduced in the eHPS group. Chest wall pressure dissipation against the resistive and viscoelastic components and elastic elastance were increased in the eHPS group. The lung resistive pressure dissipation was lower but the viscoelastic pressure was higher in the eHPS group. The airway volume proportion of collagen and elastic fibers was increased in the eHPS animals (16% and 51.7%; P<0.05 and P<0.001, respectively). The proportion of collagen volume in the vasculature increased 29% in the eHPS animals (P<0.01). HPS presents with respiratory system mechanical disarray as well as airway and vascular remodeling.     

An open-loop controlled active lung simulator for preterm infants

We describe the underlying theory, design and experimental evaluation of an electromechanical analogue infant lung to simulate spontaneous breathing patterns of preterm infants. The aim of this work is to test the possibility to obtain breathing patterns of preterm infants by taking into consideration the air compressibility. Respiratory volume function represents the actuation pattern, and pulmonary pressure and flow-rate waveforms are mathematically obtained through the application of the perfect gas and adiabatic laws. The mathematical model reduces the simulation interval into a step shorter than 1 ms, allowing to consider an entire respiratory act as composed of a large number of almost instantaneous adiabatic transformations. The device consists of a spherical chamber where the air is compressed by four cylinder-pistons, moved by stepper motors, and flows through a fluid-dynamic resistance, which also works as flow-rate sensor. Specifically designed software generates the actuators motion, based on the desired ventilation parameters, without controlling the gas pneumatic parameters with a closed-loop. The system is able to simulate tidal volumes from 3 to 8 ml, breathing frequencies from 60 to 120 bpm and functional residual capacities from 25 to 80 ml. The simulated waveforms appear very close to the measured ones. Percentage differences on the tidal volume waveform vary from 7% for the tidal volume of 3 ml, down to 2.2-3.5% for tidal volumes in the range of 4-7 ml, and 1.3% for the tidal volume equal to 8 ml in the whole breathing frequency and functional residual capacity ranges. The open-loop electromechanical simulator shows that gas compressibility can be theoretically assessed in the typical pneumatic variable range of preterm infant respiratory mechanics.     

Indirekte Bestimmung des intrapulmonalen Druckverlaufes am Lungenmodell bei Hochfrequenzbeatmung

Summary One of the determinants of intrapulmonary pressure during machine ventilation at a given time constant of the respiratory system is the duration of expiration. At high frequencies of ventilation with short expiration times substantial gas trapping can occur with end-expiratory increase in transpulmonary pressure (inadvertent PEEP). The occlusion technique allows measurement of the intrapulmonary pressure at the airway opening because of equilibration throughout the respiratory tract. The complete intrapulmonary pressure curve can be obtained, if occlusion takes place at progressively increasing intervals after the beginning of a breath. We present a computer-assisted methode for measuring the occlusion pressure at defined time points throughout the respiratory cycle.A lung simulator is ventilated by a Sechrist ventilator. The tube leading to the simulator is occluded every 5 breaths, the time point of the occlusion being advanced progressively into each breath. Occlusion pressure is compared to intrapulmonary pressure measured directly by an intrapulmonary probe. All of this is controlled by a personal computer. We are able to demonstrate that, at ventilation frequencies of up to 600/min pressure curves measured indirectly correspond sufficiently well with pressures recorded directly in the lung model. An automatic evaluation of the measurements is possible even with a tube leakage of up to 70%.

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Abkürzungen PEEP Positive end-expiratory pressure     

Assessment of mechanical ventilation parameters on respiratory mechanics

Better understanding of airway mechanics is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems in intensive-care medicine, as well as pulmonary medicine. Mechanical ventilation depends on several parameters, all of which affect the patient outcome. As there are no systematic numerical investigations of the role of mechanical ventilation parameters on airway mechanics, the objective of this study was to investigate the role of mechanical ventilation parameters on airway mechanics using coupled fluid-solid computational analysis. For the airway geometry of 3 to 5 generations considered, the simulation results showed that airflow velocity increased with increasing airflow rate. Airway pressure increased with increasing airflow rate, tidal volume and positive end-expiratory pressure (PEEP). Airway displacement and airway strains increased with increasing airflow rate, tidal volume and PEEP form mechanical ventilation. Among various waveforms considered, sine waveform provided the highest airflow velocity and airway pressure while descending waveform provided the lowest airway pressure, airway displacement and airway strains. These results combined with optimization suggest that it is possible to obtain a set of mechanical ventilation strategies to avoid lung injuries in patients.     

Bronchodilation induced by muscular contraction in spontaneously breathing rabbits: Neural or mechanical?

The respective contribution of mechanical and neural mechanisms to the bronchodilation occurring during exercise is not fully identified in spontaneously breathing animals. The airway response to electrically induced muscular contractions (MC) was studied after vagal cold block in 9 spontaneously breathing rabbits. The forced oscillation respiratory system resistance (Rrs) was measured at vagal nerve temperatures 37°C, 8°C and 4°C. Rrs was found to decrease significantly during MC in all conditions. The occasional occurrence of a deep breath was responsible for a sudden decrease in Rrs. However, when the deep breath was absent - after vagal cooling and in some experiments at 37°C - the bronchodilation was frequently dissociated from the change in breathing pattern, most likely illustrating a neural mechanism. Altogether, while some bronchodilation may be ascribed to the mechanical stretching of the airways, Rrs decreasing with little change in breathing pattern is likely related to a reflex effect, possibly a sympathetic-borne mechanism.     

Effects of mechanical load on flow, volume and pressure delivered by high-frequency percussive ventilation

High-frequency percussive ventilation (HFPV) has proved its unique efficacy in the treatment of acute respiratory distress, when conventional mechanical ventilation (CMV) has demonstrated a limited response. We analysed flow (V(dot)), volume (V) and airway pressure (Paw) during ventilation of a single-compartment mechanical lung simulator, in which resistance (R) and elastance (E) values were modified, while maintaining the selected ventilatory settings of the HFPV device. These signals reveal the physical effect of the imposed loads on the output of the ventilatory device, secondary to constant (millisecond by millisecond) alterations in pulmonary dynamics. V(dot), V and Paw values depended fundamentally on the value of R, but their shapes were modified by R and E. Although peak Paw increased 70.3% in relation to control value, mean Paw augmented solely 36.5% under the same circumstances (maximum of 9.4 cm H2O). Finally, a mechanism for washing gas out of the lung was suggested.     

Cytoskeletal remodeling of the airway smooth muscle cell: a mechanism for adaptation to mechanical forces in the lung

Airway smooth muscle is continuously subjected to mechanical forces caused by changes in lung volume during breathing. These mechanical oscillations have profound effects on airway smooth muscle contractility both in vivo and in vitro. Alterations in airway smooth muscle properties in response to mechanical forces may result from adaptive changes in the organization of the actin cytoskeleton. Recent advances suggest that in airway smooth muscle, two cytosolic signaling proteins that associate with focal adhesion complexes, focal adhesion kinase (FAK) and paxillin, are involved in transducing external mechanical signals. FAK and paxillin regulate changes in the organization of the actin cytoskeleton and the activation of contractile proteins. Actin is in a dynamic state in airway smooth muscle and undergoes polymerization and depolymerization during the contraction-relaxation cycle. The organization of the cytoskeletal proteins, vinculin, talin, and alpha-actinin, which mediate linkages between actin filaments and transmembrane integrins, is also regulated by contractile stimulation in airway smooth muscle. The fluidity of the cytoskeletal structure of the airway smooth muscle cell may be fundamental to its ability to adapt and respond to the mechanical forces imposed on it in the lung during breathing.     

Energetic parameter changes with mechanical ventilation in conjunction with BVAD assistance

The aim was to assess the influence of a biventricular assist device (BVAD) on ventricular energetics parameters (external work, oxygen consumption, cardiac mechanical efficiency) for both ventricles, when mechanical ventilation was applied. The experiments were performed using a computer simulator of cardiovascular system (CARDIOSIM) after modelling a pathological state of the left ventricle (E(v)Left = 0. 9 mmHg cm(-3) and increasing pulmonary resistance (Rap = 0.3 mmHg cm(-3 s). The effect of mechanical ventilation was mean intrathoracic pressure changes from 0 to +5 mmHg. This simulation showed that application of BVAD for both ventricles reduces external work and that this effect is stressed by positive intrathoracic pressure, reduces cardiac mechanical efficiency that is quite insensitive to intrathoracic pressure and increases oxygen consumption, which is reduced by positive intrathoracic pressure. The increase of potential energy at the onset of BVAD evidences a rightwards shift of ventricular work cycle (unloading of the ventricles). In general, positive intrathoracic pressure during BVAD assistance adversely affects ventricular energetics.     

Heterogeneous Airway Versus Tissue Mechanics and Their Relation to Gas Exchange Function During Mechanical Ventilation

We have advanced a commercially available ventilator (NPB840, Puritan Bennett/Tyco Healthcare, Pleasanton, CA) to deliver an Enhanced Ventilation Waveform (EVW). This EVW delivers a broadband waveform that contains discrete frequencies blended to provide a tidal breath, followed by passive exhalation. The EVW allows breath-by-breath estimates of frequency dependence of lung and total respiratory resistance (R) and elastance (E) from 0.2 to 8 Hz. We hypothesized that the EVW approach could provide continuous ventilation simultaneously with an advanced evaluation of mechanical heterogeneities under heterogeneous airway and tissue disease conditions. We applied the EVW in five sheep before and after a bronchial challenge and an oleic acid (OA) acute lung injury model. In all sheep, the EVW maintained gas exchange during and after bronchoconstriction, as well as during OA injury. Data revealed a range of disease conditions from mild to severe with heterogeneities and airway closures. Correlations were found between the arterial partial pressure of oxygen (P_aO2) and the levels and frequency-dependent features of R and E that are indicative of mechanical heterogeneity and tissue disease. Lumped parameter models provided additional insight on heterogeneous airway and tissue disease. In summary, information obtained from EVW analysis can provide enhanced guidance on the efficiency of ventilator settings and on patient status during mechanical ventilation.     

The effect of body warming on respiratory mechanics in rats

The temperature dependence of airway smooth muscle cells and alveolar surfactant activity, and of the elastin stress-strain relationship, suggests that body warming may affect respiratory mechanics in vivo, a possibility that has not yet been investigated. To examine this hypothesis, healthy rats were studied using the end-inflation occlusion method under control conditions and after an infrared lamp was used for body warming. Hysteresis areas, the inspiratory work of breathing, and its elastic and resistive components were also calculated. After body warming, static and dynamic elastance, ohmic airway resistance, mean value of hysteresis, the inspiratory work of breathing, and additional resistance due to pendelluft and stress relaxation were all decreased. These data suggest that body warming reduces the inspiratory work of breathing by improving the elastic and resistive mechanical properties of airways. This effect is evident even for limited temperature variations suggesting that it may occur in the event of spontaneous pathological conditions, such as fever.     

Netto-Effekte von Atembewegungen auf den Kreislauf am narkotisierten Hund

Zusammenfassung Um den mechanischen Nettoeffekt der Atembewegungen auf den Kreislauf zu bestimmen, wurden an narkotisierten Hunden die wichtigsten Kreislaufgrößen (Herzzeitvolumen, Herzfrequenz, Schlagvolumen, arterieller Blutdruck, peripherer Widerstand) vergleichend bei Atemstillstand und bei Spontanatmung oder bei künstlicher Beatmung gemessen, wobei Veränderungen der Blutgase vermieden oder ihre Effekte berücksichtigt wurden.Es wurden die folgenden wichtigsten Befunde erhoben: 1. Sowohl bei Spontanatmung als auch bei künstlicher Beatmung war die Herzfrequenz im Vergleich zum Atemstillstand erhöht (bis um 30%). 2. Bei Spontanatmung wurde diese Zunahme der Herzfrequenz von einer gleich großen Zunahme des Herzzeitvolumens begleitet. Bei künstlicher Beatmung dagegen nahm dabei das Schlagvolumen so ab, daß das Herzzeitvolumen etwa konstant blieb. 3. An vagotomierten Tieren, bei denen keine Herzfrequenzveränderungen auftraten, hatte Spontanatmung keinen Effekt auf den Kreislauf, während bei künstlicher Beatmung das Herzzeitvolumen und das Schlagvolumen im Vergleich zum Atemstillstand etwas erniedrigt waren.Aus den Befunden wurde gefolgert: 1. Künstliche und spontane Atembewegungen steigerten reflektorisch die Herzfrequenz. 2. Die künstlichen Atembewegungen an sich bedingten eine Abnahme des Schlagvolumens und des Herzzeitvolumens. 3. Die spontanen Atembewegungen an sich schienen keinen mechanischen Nettoeffekt auf den Kreislauf zu haben.

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Summary In order to determine the mechanical net effect of respiratory movements on the circulation, the principal circulatory parameters (cardiac output, cardiac frequency, stroke volume, arterial blood pressure, peripheral resistance) were measured in anesthetized dogs comparatively during apnea and during spontaneous breathing or during artificial ventilation. Changes in blood gases were avoided or their effects were taken into account.The following results were obtained: 1. During spontaneous breathing as well as during artificial ventilation the cardiac frequency was increased as compared to apnea (up to 30%). 2. During spontaneous breathing this increase in the cardiac frequency was accompanied by a corresponding increase in the cardiac output. During artificial ventilation the stroke volume decreased simultaneously in such a manner that the cardiac output remained unchanged. 3. In vagotomized animals, in which no changes of the cardiac frequency occurred, spontaneous respiration had no influence on the circulation, whereas with artificial ventilation the cardiac output and the stroke volume were decreased as compared to apnea.It was concluded from the results: 1. Artificial and spontaneous respiratory movements increased the cardiac frequency reflexly. 2. The artificial respiratory movements per se reduced the stroke volume and the cardiac output. 3. The spontaneous respiratory movements appeared to have no direct mechanical net effect on the overall circulation.

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Mit 3 Textabbildungen

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Für finanzielle Unterstützung danken wir der Bergbau-Berufsgenossenschaft, Bochum.     

Breath hold diving: In vivo model of the brain survival response in man?

Breath hold divers are faced with two main physiological challenges: pressure induced compression and extended time without breathing, exposing them to extremes of hypoxia/hypercapnia. Current world records are 214 m for depth and 11:35 min for duration. Hypoxic loss of consciousness is frequently observed during competitions. The major physiological components of the diving response that occurs during breath holding are peripheral vasoconstriction, bradycardia, decreased cardiac output, increased cerebral and myocardial blood flow, increased blood pressure, splenic contraction and preserved O(2) delivery to the brain and the heart. Sympathetic nervous activity is exceptionally engaged at the end of voluntary breath holds. We hypothesize that these adaptations to extended cessation of breathing ending with extreme hypoxia can be used as a model of brain survival response during conditions involving profound brain deoxygenation and in some instances reduced brain perfusion.     

Advanced lung ventilation system (ALVS) with linear respiratory mechanics assumption for waveform optimization of dual-controlled ventilation

The present paper describes the functional features of an advanced lung ventilation system (ALVS) properly designed for the optimization of conventional dual-controlled ventilation (DCV), i.e. with pressure-controlled ventilation with ensured tidal or minute volume. Considering the particular clinical conditions of patients treated with controlled ventilation the analysis and synthesis of ALVS control have been performed assuming a linear respiratory mechanics. Moreover, new airways pressure waveforms with more physiological shape can be tested on simulators of respiratory system in order to evaluate their clinical application. This is obtained through the implementation of a compensation procedure making the desired airways pressure waveform independent on patient airways resistance and lung compliance variations along with a complete real-time monitoring of respiratory system parameters leading the ventilator setting. The experimental results obtained with a lung simulator agree with the theoretical ones and show that ALVS performance is useful for the research activity aiming at the improvement of both diagnostic evaluation and therapeutic outcome relative to mechanical ventilation treatments.     

Successful treatment of experimental neonatal respiratory failure using extracorporeal membrane lung assist

A total of 44 preterm fetal lambs at great risk of developing respiratory failure were delivered by Cesarean section, and were then managed on conventional mechanical pulmonary ventilation. Fifteen animals initially fared well, and 14 of these were long term survivors. Twenty-nine other lambs showed a progressive deterioration in arterial blood gases within 30 minutes of delivery, of which 10 lambs were continued on mechanical pulmonary ventilation (20% survival), while the remaining 19 lambs were placed on an extracorporeal membrane lung respiratory assist (79% survival). Extracorporeal membrane lung bypass rapidly corrected arterial blood gas values, and permitted the use of high levels of CPAP instead of the continuation of mechanical pulmonary ventilation at high peak airway pressures. Improvement in lung function was gradual, and predictable. Early institution of extracorporeal respiratory assist using a membrane artificial lung rapidly corrected arterial blood gas values and significantly improved on neonate survival.     

Functional morphology and physiology of slowly adapting pulmonary stretch receptors

Since the original work by Hering and Breuer (1868) on slowly adapting pulmonary stretch receptors (SARs), numerous studies have demonstrated that these receptors are the lung vagal afferents responsible for eliciting the reflexes evoked by moderate lung inflation. SARs play a role in controlling breathing pattern, airway smooth muscle tone, systemic vascular resistance, and heart rate. Both anatomical and physiological studies support the contention that SARs, by their close association with airway smooth muscle, continuously sense the tension within the myoelastic components of the airways caused by lung inflation, smooth muscle contraction, and/or tethering of small intrapulmonary airways to the lung parenchyma. As a result, the receptor field location within the tracheobronchial tree of a SAR plays an important role in its discharge pattern, with variations in airway transluminal pressure and airway smooth muscle orientation being important modulating factors. The disruption of airway myoelastic components in various pulmonary diseases would be expected to alter the discharge pattern of SARs, and contribute to changes in breathing pattern and airway smooth muscle tone.