Search

Pulmonary atelectasis is common in the perioperative period. Physiologically, it is produced when collapsing forces derived from positive pleural pressure and surface tension overcome expanding forces from alveolar pressure and parenchymal tethering. Atelectasis impairs blood oxygenation and reduces lung compliance. It is increasingly recognized that it can also induce local tissue biologic responses, such as inflammation, local immune dysfunction, and damage of the alveolar–capillary barrier, with potential loss of lung fluid clearance, increased lung protein permeability, and susceptibility to infection, factors that can initiate or exaggerate lung injury. Mechanical ventilation of a heterogeneously aerated lung (e.g., in the presence of atelectatic lung tissue) involves biomechanical processes that may precipitate further lung damage: concentration of mechanical forces, propagation of gas–liquid interfaces, and remote overdistension. Knowledge of such pathophysiologic mechanisms of atelectasis and their consequences in the healthy and diseased lung should guide optimal clinical management.

Mean airway pressure (Pmean) is a common pressure monitoring parameter of mechanical ventilators that is closely correlated with mean alveolar pressure and represents stresses applied to the lung parenchyma during ventilation. Pmean is determined by the peak inspiratory pressure, positive end-expiratory pressure (PEEP), and inspiratory-to-expiratory time ratio with dynamic and real-time characteristics, which represents mechanical power affected by the ventilator mode. Additionally, Pmean is an important parameter that affects hemodynamics. Tidal forces and PEEP increase pulmonary vascular resistance (PVR) in direct proportion to their effects on Pmean. Therefore, Pmean is increasingly considered to be related to the prognosis of patients on mechanical ventilation. We propose a 3P strategy (Pmean, central venous pressure [CVP], and perfusion index [PI]) which is indicated to achieve circulation protection mechanical ventilation with flow priority. Titrating the appropriate CVP and meeting PI to ensure tissue perfusion with a lower Pmean are the core purposes. Pmean links the circulatory and respiratory systems and is expected to become a potential parameter for intelligent ventilation.

Background Complete airway closure during expiration may underestimate alveolar pressure. It has been reported in cases of acute respiratory distress syndrome (ARDS), as well as in morbidly obese patients with healthy lungs. The authors hypothesized that complete airway closure was highly prevalent in obese ARDS and influenced the calculation of respiratory mechanics. Methods In a post hoc pooled analysis of two cohorts, ARDS patients were classified according to body mass index (BMI) terciles. Low-flow inflation pressure-volume curve and partitioned respiratory mechanics using esophageal manometry were recorded. The authors' primary aim was to compare the prevalence of complete airway closure according to BMI terciles. Secondary aims were to compare (1) respiratory system mechanics considering or not considering complete airway closure in their calculation, and (2) and partitioned respiratory mechanics according to BMI. Results Among the 51 patients analyzed, BMI was less than 30 kg/m in 18, from 30 to less than 40 in 16, and greater than or equal to 40 in 17. Prevalence of complete airway closure was 41% overall (95% CI, 28 to 55; 21 of 51 patients), and was lower in the lowest (22% [3 to 41]; 4 of 18 patients) than in the highest BMI tercile (65% [42 to 87]; 11 of 17 patients). Driving pressure and elastances of the respiratory system and of the lung were higher when complete airway closure was not taken into account in their calculation. End-expiratory esophageal pressure (ρ = 0.69 [95% CI, 0.48 to 0.82]; P Conclusions Prevalence of complete airway closure was high in ARDS and should be taken into account when calculating respiratory mechanics, especially in the most morbidly obese patients. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Plateau and driving pressures have been shown to correlate with mortality in adult respiratory distress syndrome (ARDS). However, these static airway pressures may not always accurately reflect alveolar pressure.It has recently been recognized that in ARDS, airway closure may occur while some alveoli are still inflated. This may result in a biased estimate of mean alveolar pressure.Complete airway closure can only be measured by the inflection point on the initial portion of a low-flow inflation pressure-volume or pressure-time curve with the absence of cardiac oscillations and very low compliance, most likely in the terminal bronchioles.In 25 to 33% of patients with ARDS, airway opening pressure (the inflection point value) is greater than the total positive end-expiratory pressure measured by an end-expiratory maneuver. What this article tells us that is new In a post hoc analysis of two cohort studies of respiratory mechanics in ARDS, the authors compared the prevalence of complete airway closure stratified by body mass index and its effects on respiratory mechanics.Complete airway closure was present in 41% of patients, increasing with body mass index tercile (65% in the highest).Driving pressure and respiratory system elastances (lung, chest wall) were higher when complete airway closure was not adjusted for.

During spontaneous breathing at rest, the alveolar pressure (Palv)-flow (V) relation exhibits a prominent expiratory loop in many chronic obstructive pulmonary disease (COPD) patients. Among the possible determinants of the loop, tidal expiratory flow limitation (tEFL) may be the main responsible. To compare the characteristics of the expiratory loop in COPD patients with flow limitation (FL) and without flow limitation (NFL), tEFL was assessed with the negative expiratory pressure technique in stable mild to very severe COPD patients undergoing body plethysmography before and after bronchodilation (BD), an intervention that is able to reduce mechanical heterogeneity, recruitment/derecruitment, and gas trapping but rarely abolishes tEFL. The magnitude of the expiratory loop was indexed by the integral of Palv on V during expiration (Aexp). Before BD, Aexp was 360% greater in FL (n = 35) than in NFL (n = 25) patients (P < 0.001). After BD, Aexp was unchanged in NFL patients (ΔAexp 0%, P = 0.882) and slightly decreased in FL patients who remained FL (n = 32, ΔAexp -17%, P = 0.064). Three FL patients became NFL after BD, and their Aexp decreased markedly (ΔAexp -61%), reaching values similar to those observed in NFL patients at baseline. In conclusion, the greater Aexp measured in FL relative to NFL COPD patients, its relative invariance after BD when flow limitation persists, and its fall when flow limitation is abolished indicate that tEFL is a major determinant of the magnitude of the expiratory loop. Furthermore, Aexp can be used as a predictor of the presence of tEFL.NEW & NOTEWORTHY In stable chronic obstructive pulmonary disease (COPD) patients spontaneously breathing at rest, tidal expiratory flow limitation is the major determinant of the occurrence of expiratory looping in the plethysmographic flow-alveolar pressure diagram. In these patients the magnitude and the characteristics of the loop can be used as predictors of the presence of tidal expiratory flow limitation.

Often, in supporting patients suffering from severe respiratory diseases with mechanical ventilation, obstacles are encountered due to pulmonary and/or thoracic alterations, reductions in the ventilable lung parenchyma, increases in airway resistance, alterations in thoraco-pulmonary compliance, advanced age of the subjects. All this involves difficulties in finding the right ventilation parameters and an adequate driving pressure to guarantee sufficient ventilation. Therefrom, new mechanical ventilation techniques were sought that could help overcome the aforementioned obstacles. A new mode of mechanical ventilation is being presented, i.e., a Positive + Negative Synchronized Ventilation (PNSV), characterized by the association and integration of two pulmonary ventilators; one acting inside the chest with positive pressures and one externally with negative pressure. The peculiarity of this combination is the complete synchronization, which takes place with specific electronic modifications. The PNSV can be applied both in a completely non-invasive and invasive way and, therefore, be used both in acute care wards and in ICU. The most relevant effect found, due to the compensation of opposing pressures acting on the chest, is that, during the entire inspiratory act created by the ventilators, the pressure at the alveolar level is equal to zero even if adding together the two ventilators’ pressures; thus, the transpulmonary pressure is doubled. The application of this pressure for 1 hour on elderly patients suffering from severe acute respiratory failure, resulted in a significant improvement in blood gas analytical and clinical parameters without any side effects. An increased pulmonary recruitment, including posterior lung areas, and a reduction in spontaneous ventilatory rate have also been demonstrated with PNSV. This also paves the way to the search for the best ventilatory treatment in critically ill or ARDS patients. The compensation of intrathoracic pressures should also lead, although not yet proven, to an improvement in venous return, systolic and cardiac output. In the analysis of the study in which this method was applied, the total transpulmonary pressure delivered was the sum of the individual pressures applied by the two ventilators. However, this does not exclude the possibility of reducing the pressures of the two machines to modulate a lower but balanced total transpulmonary pressure within the chest.

In the review we have discussed the mechanisms of the changes of the venous return and pulmonary hemodynamics which take place in clinical cases of the mechanical lung ventilation with positive end-expiratory pressure. In these conditions the elevating of right atrial pressure does not cause the decreasing of the venous return, because the mean circulatory filling pressure also increases. Thus, the gradient for venous return remains relatively constant. In case of the mechanical lung ventilation with positive end-expiratory pressure the decreasing of the venous return is the result of the elevation of the venous resistance as consequence of the direct increasing of the intrathoracic and transdiaphragmatic pressures and activation of the reflectory neurogenic mechanisms. In the conditions, indicated above, the increased alveolar pressure leads to the improvement of the diffused lung capacity for oxygen, which decreases the manifestations of the hypoxic pulmonary vasoconstriction and thus diminishes pulmonary vascular resistance. The character of changes of the last one is determined by the reactions of the two types (alveolar and extraalveolar) intraparenchimal pulmonary vessels. This leads to the changes of the resistive and capacitive functions of the pulmonary vessels. In case of the high levels of the positive end-expiratory pressure (more than 30 cm of water column) the value of alveolar pressure is comparable or even more excessive than pulmonary artery pressure (1216 mm Hg), which can be the reason of the decreasing of the right ventricular contractility and the venous return. The increasing of the capillary filtration coefficient of pulmonary vessels in the conditions of the mechanical lung ventilation with positive end-expiratory pressure can be the result of the activation of the mechanosensitive transient receptor potential vanilloid-4 (TRPV4) channels and the increasing endothelial calcium entry.

Background Recent analyses of patient data in acute respiratory distress syndrome (ARDS) showed that a lower ventilator driving pressure was associated with reduced relative risk of mortality. These findings await full validation in prospective clinical trials. Methods To investigate the association between driving pressures and ventilator induced lung injury (VILI), we calibrated a high fidelity computational simulator of cardiopulmonary pathophysiology against a clinical dataset, capturing the responses to changes in mechanical ventilation of 25 adult ARDS patients. Each of these in silico patients was subjected to the same range of values of driving pressure and positive end expiratory pressure (PEEP) used in the previous analyses of clinical trial data. The resulting effects on several physiological variables and proposed indices of VILI were computed and compared with data relating ventilator settings with relative risk of death. Results Three VILI indices: dynamic strain, mechanical power and tidal recruitment, showed a strong correlation with the reported relative risk of death across all ranges of driving pressures and PEEP. Other variables, such as alveolar pressure, oxygen delivery and lung compliance, correlated poorly with the data on relative risk of death. Conclusions Our results suggest a credible mechanistic explanation for the proposed association between driving pressure and relative risk of death. While dynamic strain and tidal recruitment are difficult to measure routinely in patients, the easily computed VILI indicator known as mechanical power also showed a strong correlation with mortality risk, highlighting its potential usefulness in designing more protective ventilation strategies for this patient group. Electronic supplementary material The online version of this article (10.1186/s12931-019-0990-5) contains supplementary material, which is available to authorized users.

The focus of this chapter is on understanding the complexity associated with the resistance to flow through the pulmonary circulation. Pulmonary vascular resistance (PVR) is a variable that reflects the physical size (diameter and length) of the vascular tree at any moment in time. If PVR is increased, then it will take more energy for the right ventricle to pump the venous return through the lungs. One obvious complexity with the magnitude of the PVR is that the pulmonary resistance changes with lung inflation. There may also be resistance changes in response to various stimuli, as well as in different lung pathologies, and it can play an important role in the impact of heart–lung interactions. Although it is easy to define pulmonary resistance analogous to Ohm’s law, the underlying basis of pathophysiologic changes in this resistance is neither simple nor always intuitive, and it is important to understand the limitations of this measurement. A fundamental issue in the interpretation (or even definition) of PVR involves uncertainty about what downstream pressure to use (and how to measure it in vivo). A ubiquitous understanding of the pulmonary vasculature today revolves around the three zones of the lung as defined by West et al. In an upright human, a certain fraction of the lung would be in a zone 2 condition, where alveolar pressure becomes the effective downstream pressure. However, at any given time, there will always be a mixture of zones in the pulmonary circulation, so how can one define or measure the PVR? In addition to this puzzle, there are changes in PVR related to the effect of lung inflation on different serial regions of the pulmonary vasculature, as well as effects of the nonlinear distensibility of the elastic vessels. In what follows, we deal with these issues in an effort to define when and where it might be appropriate to measure the PVR, and more importantly how it might be useful in physiologic research and clinical settings.

Intrapleural pressure during a forced vital capacity (VC) maneuver is often in excess of that required to generate maximal expiratory airflow. This excess pressure compresses alveolar gas (i.e., thoracic gas compression [TGC]), resulting in underestimated forced expiratory flows (FEFs) at a given lung volume. It is unknown if TGC is influenced by sex; however, because men have larger lungs and stronger respiratory muscles, we hypothesized that men would have greater TGC. We examined TGC across the “effort‐dependent” region of VC in healthy young men (n = 11) and women (n = 12). Subjects performed VC maneuvers at varying efforts while airflow, volume, and esophageal pressure (POES) were measured. Quasistatic expiratory deflation curves were used to obtain lung recoil (PLUNG) and alveolar pressures (i.e., PALV = POES–PLUNG). The raw maximal expiratory flow–volume (MEFVraw) curve was obtained from the “maximum effort” VC maneuver. The TGC‐corrected curve was obtained by constructing a “maximal perimeter” curve from all VC efforts (MEFVcorr). TGC was examined via differences between curves in FEFs (∆FEF), area under the expiratory curves (∆AEX), and estimated compressed gas volume (∆VGC) across the VC range. Men displayed greater total ∆AEX (5.4 ± 2.0 vs. 2.0 ± 1.5 L2·s−1; p, We sought to examine whether sex influences the degree to which thoracic gas compression (TGC) underestimates forced expiratory flows at a given lung volume during forced expiration. Men displayed greater TGC than women, particularly at 25% of the forced expired volume. This greater TGC was likely due to greater expiratory pressures generated by men throughout the maneuver. Failure to appropriately account for TGC results in a greater underestimation of expiratory airflow in men, primarily during the early phase of forced expiration.

The relationship between regional variabilities in airflow (ventilation) and blood flow (perfusion) is a critical determinant of gas exchange efficiency in the lungs. Hypoxic pulmonary vasoconstriction is understood to be the primary active regulator of ventilation-perfusion matching, where upstream arterioles constrict to direct blood flow away from areas that have low oxygen supply. However, it is not understood how the integrated action of hypoxic pulmonary vasoconstriction affects oxygen transport at the system level. In this study we develop, and make functional predictions with a multi-scale multi-physics model of ventilation-perfusion matching governed by the mechanism of hypoxic pulmonary vasoconstriction. Our model consists of (a) morphometrically realistic 2D pulmonary vascular networks to the level of large arterioles and venules; (b) a tileable lumped-parameter model of vascular fluid and wall mechanics that accounts for the influence of alveolar pressure; (c) oxygen transport accounting for oxygen bound to hemoglobin and dissolved in plasma; and (d) a novel empirical model of hypoxic pulmonary vasoconstriction. Our model simulations predict that under the artificial test condition of a uniform ventilation distribution (1) hypoxic pulmonary vasoconstriction matches perfusion to ventilation; (2) hypoxic pulmonary vasoconstriction homogenizes regional alveolar-capillary oxygen flux; and (3) hypoxic pulmonary vasoconstriction increases whole-lobe oxygen uptake by improving ventilation-perfusion matching., Author summary The relationship between regional ventilation (airflow) and perfusion (blood flow) is a major determinant of gas exchange efficiency. Atelactasis and pulmonary vascular occlusive diseases, such as acute pulmonary embolism, are characterized by ventilation-perfusion mismatching and decreased oxygen in the bloodstream. Despite the physiological and medical importance of ventilation-perfusion matching, there are gaps in our knowledge of the regulatory mechanisms that maintain adequate gas exchange under pathological and normal conditions. Hypoxic pulmonary vasoconstriction is understood to be the primary regulator of ventilation-perfusion matching, where upstream arterioles constrict to direct blood flow away from areas that have low oxygen supply, yet it is not understood how this mechanism affects oxygen transport at the system level. In this study we present a computational model of the ventilation-perfusion matching and hypoxic pulmonary vasoconstriction to better understand how physiological regulation at the regional level scales to affect oxygen transport at the system level. Our model simulations predict that this regulatory mechanism improves the spatial overlap of airflow and blood flow, which serves to increase the uptake of oxygen into the bloodstream. This improved understanding of ventilation-perfusion matching may offer insights into the etiology of, and therapeutic interventions for diseases characterized by ventilation-perfusion mismatching.

Supplemental Digital Content is available in the text., Objectives: Elucidate how the degree of ventilator-induced lung injury due to atelectrauma that is produced in the injured lung during mechanical ventilation is determined by both the timing and magnitude of the airway pressure profile. Design: A computational model of the injured lung provides a platform for exploring how mechanical ventilation parameters potentially modulate atelectrauma and volutrauma. This model incorporates the time dependence of lung recruitment and derecruitment, and the time-constant of lung emptying during expiration as determined by overall compliance and resistance of the respiratory system. Setting: Computational model. Subjects: Simulated scenarios representing patients with both normal and acutely injured lungs. Measurements and Main Results: Protective low-tidal volume ventilation (Low-Vt) of the simulated injured lung avoided atelectrauma through the elevation of positive end-expiratory pressure while maintaining fixed tidal volume and driving pressure. In contrast, airway pressure release ventilation avoided atelectrauma by incorporating a very brief expiratory duration () that both prevents enough time for derecruitment and limits the minimum alveolar pressure prior to inspiration. Model simulations demonstrated that has an effective threshold value below which airway pressure release ventilation is safe from atelectrauma while maintaining a tidal volume and driving pressure comparable with those of Low-Vt. This threshold is strongly influenced by the time-constant of lung-emptying. Conclusions: Low-Vt and airway pressure release ventilation represent markedly different strategies for the avoidance of ventilator-induced lung injury, primarily involving the manipulation of positive end-expiratory pressure and , respectively. can be based on exhalation flow values, which may provide a patient-specific approach to protective ventilation.

The equal pressure point (EPP) states that expiratory flow limitation occurs at the precise location along the tracheobronchial tree where intraluminal and peribronchial pressures are equal (i.e., where the local transmural pressure is 0 cmH2O). The EPP may be determined numerically via the expiratory isovolume pressure flow (IVPF) curve. For instance, using data from a given isovolume curve, the EPP is determined as the point along the x‐axis at which pressure‐flow data fails to conform to Rohrer’s equation: driving pressure = k1(flow) + k2(flow2). The probability of incurring expiratory flow‐limitation can be greatly determined by the EPP such that a lower EPP at a given lung volume requires only minimal pressure development to create a flow‐limiting segment during expiration. The EPP is affected by two principal factors: lung elastic recoil (PLUNG) & airway geometry. Given recent evidence suggesting that airway geometry is different between men & women, we sought to determine whether the EPP is likewise affected by sex in healthy adults. Purpose Determine whether or not there is an effect of sex on the magnitude of the EPP. Methods To address this question, 11 men (23.1 ± 4.8 years) and 12 women (21.2 ± 1.0 years) completed a study requiring two visits to the laboratory. On the initial visit, we obtained written informed consent and conducted spirometry to ensure subjects met the inclusion criteria of normal (>85% of predicted) lung function. During the second visit, a balloon catheter was passed intranasally to the lower one‐third of the esophagus and remained there for the duration of the visit to measure esophageal pressure (PES). Subjects then performed a minimum of 10–15 graded vital capacity maneuvers from 100‐5% of maximal effort. Data were imported into Matlab and, using custom‐written code, multiple calculations were performed. First, the lowest effort vital capacity efforts were taken as quasi‐static expiratory deflations of the lung and the negative sign of PES was taken to equal PLUNG. Second, alveolar pressure (PALV) was taken to equal PES + PLUNG. Finally, the EPP was determined by iteratively fitting Rohrer’s equation to pressure‐flow data at a given iso‐volume. The pressure at which Rohrer’s equation no longer adequately fit the data (>5% error) was termed the EPP. To test for an effect of sex and lung volume, a two‐way ANOVA was computed. Pairwise comparisons were adjusted for multiple comparisons using the Tukey‐Sidak post hoc test. Results There was no effect of sex on PLUNG, but PALV was greater in men than women throughout the entire VC range. EPP was significantly greater in men than women during the initial half of VC (95‐55% of VC) (p 0.05). Conclusion Because PLUNG did not differ between men and women, the differing location of EPP was the result of a greater PES in men. This suggests that the larger airways present in men are more resistant to compression than those of women.

Airway transmural pressure in healthy homogeneous lungs with dilated airways is approximately equal to the difference between intraluminal and pleural pressure. However, bronchoconstriction causes airway narrowing, parenchymal distortion, dynamic hyperinflation, and the emergence of ventilation defects (VDefs) affecting transmural pressure. This study aimed to investigate the changes in transmural pressure caused by bronchoconstriction in a bronchial tree. Transmural pressures before and during bronchoconstriction were estimated using an integrative computational model of bronchoconstriction. Briefly, this model incorporates a 12-generation symmetric bronchial tree, and the Anafi and Wilson model for the individual airways of the tree. Bronchoconstriction lead to the emergence of VDefs and a relative increase in peak transmural pressures of up to 84% compared to baseline. The highest increase in peak transmural pressure occurred in a central airway outside of VDefs, and the lowest increase was 27% in an airway within VDefs illustrating the heterogeneity in peak transmural pressures within a bronchial tree. Mechanisms contributing to the increase in peak transmural pressures include increased regional ventilation and dynamic hyperinflation both leading to increased alveolar pressures compared to baseline. Pressure differences between intraluminal and alveolar pressure increased driven by the increased airway resistance and its contribution to total transmural pressure reached up to 24%. In conclusion, peak transmural pressure in lungs with VDefs during bronchoconstriction can be substantially increased compared to dilated airways in healthy homogeneous lungs and is highly heterogeneous. Further insights will depend on the experimental studies taking these conditions into account.

Dynamic hyperinflation occurs when mean alveolar pressure exceeds the mean airway pressure measured in the airway opening. The dynamic hyperinflation develops as a consequence of insufficiently long expiration terminated by the subsequent inspiration. Two main principles are supposed to create the dynamic hyperinflation during high frequency oscillatory ventilation (HFOV): expiratory flow limitation and different inspiratory and expiratory airway resistances (Re > Ri). The aim of the study is to design and test a physical model of the respiratory system comprising both the mechanisms causing dynamic hyperinflation and to characterize their effect upon dynamic hyperinflation or hypoinflation development during HFOV. The models were created using a rigid volume and passive pneumatic components mimicking the required characteristics of the airway resistance. The models were connected to a HFOV ventilator and different ventilator settings were applied in order to investigate the parameters having the most significant effect on dynamic hyperinflation development. The main result of the study is that the expiratory flow limitation corresponds better with the observed and published properties of the respiratory system during HFOV. The magnitude of dynamic hyperinflation depends on ventilator setting. The acquired results are supported by recently published studies using mathematical-physical modeling and correspond with results of the published clinical trials.

Plethysmographic alveolar pressure-flow (Palv-F) loops contain potentially relevant information about the pathophysiology of chronic obstructive pulmonary disease (COPD), but no quantitative analysis of these loops during spontaneous breathing has ever been performed. The area of the loop's inspiratory (Ains) and expiratory portion (Aexp), and the difference between the end-expiratory and end-inspiratory alveolar pressure (ΔPalv) were measured in 20 young, 20 elderly healthy subjects, and 130 stable COPD patients. Ains and ΔPalv increased by 55 and 78% from young to elderly subjects, and by 107 and 122% from elderly subjects to COPD patients, reflecting changes in mechanical heterogeneity, lung-units recruitment/derecruitment, and possibly air trapping occurring with aging and/or obstructive disease. Aexp increased by 38% from young to elderly subjects, and by 198% from elderly subjects to COPD patients, consistent with the additional contribution of tidal expiratory flow-limitation, which occurs only in COPD patients and affects Aexp only. In COPD patients, Aexp and ΔPalv showed a significant negative correlation with VC, FEV1, IC, and a significant positive correlation with RV/TLC. The results suggest that the analysis of plethysmographic Palv-F loops provides an insight of the pathophysiological factors, especially tidal expiratory flow-limitation, that affect lung function in COPD patients.

The research goal was to formulate and substantiate the hypothesis explaining support for an expiratory air flow in case of pulmonary emphysema. The research method consisted in comparing the mechanical properties of lungs in practically healthy individuals (37 individuals, mean age – (30.4 ± 1.7) y.o.) and COPD patients with pronounced lung emphysema (30 patients, mean age – (52.1 ± 2.3) y.o.) as well as those of isolated normal lungs (n = 14) and isolated lungs of patients who died of COPD (n = 5). Pulmo-nary mechanics was studied via the simultaneous measurement of transpulmonary pressure and lung ven-tilation volume. General lung hysteresis and elastic lung hysteresis were calculated. The mechanical properties of isolated lungs were studied using passive ventilation under the Donders bell. The air flow was interrupted in order to measure alveolar pressure and develop an elastic lung hysteresis curve. Pres-sure in the Donders bell was changed by means of a special pump in automatic and manual modes. The research has not revealed any fundamental differences between the mechanical properties of the normal and emphysematous lungs. A minimum increase in the pressure inside the Donders bell over atmospheric pressure used to stop air ejection in both normal and the emphysematous lungs as the result of flap-valve bronchial obstruction. In living beings, air is ejected from lungs with an increase in pressure under the conditions of forced expiration. Pressure increases up to (38.6 ± 2.71) cm H2O in healthy individuals and up to (20.5 ± 1.86) cm H2O in COPD patients. Probably, an expiratory air flow is supported by active expiratory bronchial dilatation that counteracts flap-valve bronchial obstruction. The hypothesis is based on the confirmed ability of the lungs to perform inspiratory actions (in addition to the action of respiratory muscles) and the theory of mechanical lung activity.

Background: Acute respiratory acidosis is associated with alterations in diaphragm performance. The authors compared the effects of respiratory acidosis and metabolic acidosis in the rat diaphragm in vitro. Methods: Diaphragmatic strips were stimulated in vitro, and mechanical and energetic variables were measured, cross-bridge kinetics calculated, and the effects of fatigue evaluated. An extracellular pH of 7.00 was obtained by increasing carbon dioxide tension (from 25 to 104 mmHg) in the respiratory acidosis group (n = 12) or lowering bicarbonate concentration (from 24.5 to 5.5 mM) in the metabolic acidosis group (n = 12) and the results compared with a control group (n = 12, pH = 7.40) after 20-min exposure. Results: Respiratory acidosis induced a significant decrease in maximum shortening velocity (−33%, P < 0.001), active isometric force (−36%, P < 0.001), and peak power output (−59%, P < 0.001), slowed relaxation, and decreased the number of cross-bridges (−35%, P < 0.001) but not the force per cross-bridge, and impaired recovery from fatigue. Respiratory acidosis impaired more relaxation than contraction, as shown by impairment in contraction–relaxation coupling under isotonic (−26%, P < 0.001) or isometric (−44%, P < 0.001) conditions. In contrast, no significant differences in diaphragmatic contraction, relaxation, or contraction–relaxation coupling were observed in the metabolic acidosis group. Conclusions: In rat diaphragm, acute (20 min) respiratory acidosis induced a marked decrease in the diaphragm contractility, which was not observed in metabolic acidosis.

Two functional levels of mechanical energy intrapulmonary source have been viewed in this article for the first time. The first level is located into the perialveolar space. This level provides inspiratory and expiratory activity of the lungs together with respiratory muscles. Due to this, the inspiratory alveolar pressure is lower than the intrapleural pressure and the expiratory alveolar pressure is higher than the intrapleural pressure. This is deter mined by work of breathing measured as negative elastic hysteresis area and allows overcoming some nonelastic resistance of the lungs. The lung activity on overcoming the elastic resistance is estimated by multiplying the total work of breathing by a functional coefficient of lung elasticity (FCLE). The latter is calculated by dividing the total lung compliance by the dynamic lung compliance and reflects change in the elastic lung tension from spontaneous breathing level to the total lung compliance level. FCLE approximates 1 in healthy subjects and in patients with normal lung elastic recoil (LER). LER is lower and the total lung capacity is higher in lung obstructive diseases. Consequently, the total lung compliance could increase and FCLE could grow up to 10 in such cases (for instance, in severe emphysema). This leads to increasing lung activity on overcoming the elastic resistance up to 10 kgf × m / min or higher. Actually, this huge work of breathing is not performed due to the 2nd level of lung mechanical activity that is an active dilation of the large airways on expiration; this mechanism prevents valvular bronchial obstruction.

Background: A non-invasive means of measuring pulmonary blood flow (PBF) would have numerous benefits in medicine. Tradition ally, respiratory-based methods require breathing maneuvers, partial rebreathing, or foreign gas mixing because exhaled CO2 volume on a per-breath basis does not accurately represent alveolar exchange of CO2. We hypothesized that if the dilutional effect of the functional residual capacity was accounted for, the relationship between the calculated volume of CO2 removed per breath and the alveolar partial pressure of CO2 would be reversely linear. Methods: A computer model was developed that uses variable tidal breathing to calculate CO2 removal per breath at the level of the alveoli. We iterated estimates for functional residual capacity to create the best linear fit of alveolar CO 2 pressure and CO2 elimination for 10 minutes of breathing and incorporated the volume of CO2 elimination into the Fick equation to calculate PBF. Results: The relationship between alveolar pressure of CO2 and CO2 elimination produced an R 2 = 0.83. The optimal functional residual capacity differed from the “actual” capacity by 0.25 L (8.3%). The repeatability coefficient leveled at 0.09 at 10 breaths and the difference between the PBF calculated by the model and the preset blood flow was 0.62 ± 0.53 L/minute. Conclusions: With variations in tidal breathing, a linear relationship exists between alveolar CO2 pressure and CO2 elimination. Existing technology may be used to calculate CO2 elimination during quiet breathing and might therefore be used to accurately calculate PBF in humans with healthy lungs.

Spirometry is the gold standard to detect airflow limitation, but it does not measure airway resistance, which is one of the physiological factors behind airflow limitation. In this study, we describe the dynamics of forced expiration in spirometry using a deflating balloon and using this model. We propose a methodology to estimate &zeta, (zeta), a dimensionless and effort-independent parameter quantifying airway resistance. In N = 462 (65 &plusmn, 8 years), we showed that &zeta, is significantly (p &lt, 0.0001) greater in COPD (2.59 &plusmn, 0.99) than healthy smokers (1.64 &plusmn, 0.18), it increased significantly (p &lt, 0.0001) with the severity of airflow limitation and it correlated significantly (p &lt, 0.0001) with airway resistance (r = 0.55) and specific conductance (r = &minus, 0.60) obtained from body-plethysmography. &zeta, also showed significant associations (p &lt, 0.001) with diffusion capacity (r = &minus, 0.64), air-trapping (r = 0.68), and CT densitometry of emphysema (r = 0.40 against % below &minus, 950 HU and r = &minus, 0.34 against 15th percentile HU). Moreover, simulation studies demonstrated that an increase in &zeta, resulted in lower airflows from baseline. Therefore, we conclude that &zeta, quantifies airway resistance from forced expiration in spirometry&mdash, a method that is more abundantly available in primary care than traditional but expensive methods of measuring airway resistance such as body-plethysmography and forced oscillation technique.

Exercise-induced pulmonary haemorrhage is a major cause of poor performance in the equine athlete. It is an important cause of exercise intolerance and results from strenuous exercise and pathophysiological changes in the equine lung and possibly in the airways. Endoscopic surveys of the respiratory tracts of horses after competitive events have shown that many horses experience exercise-induced pulmonary haemorrhage. The reported incidence of exercise-induced pulmonary haemorrhage in different breeds varies between 40–85%. The cause of bleeding in exercising horses has fostered considerable debate over the past three centuries, but currently, the most accepted hypothesis is that the source of haemorrhage is disruption of the pulmonary capillaries during exercise. Furosemide is the medication used most widely for the treatment and prevention of exercise-induced pulmonary haemorrhage. This review provides an update on the aetiology, clinical signs, physiopathology, diagnosis and treatment of exercise-induced pulmonary haemorrhage. EIPH, pulmonary pressure, equine The clinical signs of pulmonary bleeding after exercise in horses were first described by Markham (1688). Robertson (1913) reported the existence of epistaxis in racehorses, attributing it to a hyperaemic condition of the pulmonary vessels. Later, the epistaxis was attributed to an inherited condition in thoroughbred racehorses. Despite the time that has passed since the conditions of disease were first described, the cause of the disease and the optimal approach to treatment has not been established yet. According to Hinchcliff (2000), this phenomenon should not be considered a disease as such, but rather a common condition in sport horses. Other authors noted that bleeding after exercise is a physiological phenomenon related to extreme exercise, as the horse is genetically prepared for prolonged physical effort but with submaximal speed (West and Mathieu-Costello 1995). As stated by Derksen et al. (1992), the term that best describes this bleeding after athletic stress in horses is Exercise-Induced Pulmonary Haemorrhage (EIPH). This condition is defined as the presence of blood in the tracheobronchal circulation derived from the alveolar capillaries (Sweeney 1991). Its importance lies in the high incidence of this condition in sport horses; according to some authors, between 42 to 85% of horses that perform at high speeds suffer from it (Hillidge and Whitlock 1986; Birks et al. 2002, Newton and Wood 2002; Moran et al. 2003; Araya et al. 2007). Currently, the most accepted hypothesis regarding the origin and mechanism of EIPH involves the rupture of pulmonary capillaries during exercise (Poole et al. 2007). Predisposing factors for exercise-induced pulmonary haemorrhage Exercise-induced pulmonary haemorrhage does not have a single aetiologic factor such as race, sport, age, sex, environment or horse management, but it is supported by the coexistence of multiple predisposing factors (Art and Lekeux 1994). Many authors agree that the occurrence of EIPH is caused by effort, training or career (West et al. 1993). Horses subjected to high-speed sprinting that induces a heart rate of 240/min will suffer EIPH during the race or after it (Harkins et al. 1997). It is thought that the rate ACTA VET. BRNO 2013, 82: 309–316; doi:10.2754/avb201382030309 Address for correspondence: Gabriel Moran Department of Pharmacology, Faculty of Veterinary Science Universidad Austral de Chile, Valdivia, Chile Phone: +56-63-221936 Fax: +56-63-221444 E-mail: gmoran@uach.cl http://actavet.vfu.cz/ of acceleration of 17 m/s, which develops at the start of the race, causes an increase in pulmonary intravascular pressure and leads to EIPH (Erickson 1992). It has been found that pulmonary arterial pressure and venous pressure can reach 100 mmHg and 80 mmHg during peak exercise, respectively. Because pulmonary capillary pressure is in between the pulmonary arterial and venous pressure values, it has been estimated that pulmonary capillary pressure approaches 90–95 mmHg during intense exercise (Langsetmo et al. 2000). These changes in pressure, accompanied by a negative pleural pressure and largevolume ventilation during maximal exercise may induce transmural capillary pressure that breaks the endothelial cell junctions in the alveolar epithelium, which ruptures the pulmonary capillaries (Manohar et al. 1993; West and Mathieu-Costello, 1994, 1995; Deksen et al. 2001). It has been shown that there is insufficient gas exchange due to the disruption of pulmonary capillaries, which suffer from arterial hypoxaemia and hypercapnia, which leads to increased anaerobic metabolism (Manohar et al. 2001; Caillaud et al. 2002). The fact that EIPH occurs after high-intensity exercise and prolonged low-intensity exercise suggests that this problem is due to extreme mechanical stresses on the tissue and pulmonary vessels during exercise (Art and Lekeux 1994). However, West et al. (1993) observed episodes of EIPH in horses just after walking and trotting. There is a trend related to age, where older horses have shown increased susceptibility to episodes of EIPH (Lapointe et al. 1994). Derksen (2009) suggested that increased prevalence of EIPH in older horses is due to progressive lung damage from repeated episodes of bleeding and the development of diseases of the upper airways. On the other hand, Oikawa (1999) showed that the equine lung is vulnerable to post-stress bleeding in individuals aged between 18 and 22 months. In addition, this part is vulnerable to trauma during exercise especially by the scapulo-humeral joint, where the forces are transmitted actively through the chest wall to reach the lung parenchyma (Newton et al. 2005). This may be because the scapula acts as a hinge to the spine, so that a portion of its surface moves toward the ribs plus some surrounding muscles may move medially (Schroter et al. 1998). Some authors have mentioned that the risk of developing EIPH cannot be readily determined from a combination of age, environment, race speed, race distance, track hardness or air quality (Hinchcliff et al. 2010). Possible causes of exercise-induced pulmonary haemorrhage The real causes of EIPH are still unknown. Numerous causes and pathophysiological mechanisms for the development of this disease have been proposed. These include infectious pulmonary diseases, which facilitate the development of fundamental EIPH by weakening the alveolar capillary walls and thus facilitating their rupture (McKane and Slocombe 2002), diseases of the lower airways, higher airway obstruction (Cook et al. 1988), blood hyperviscosity induced by exercise (Fedde and Wood 1993; Weiss and Smith 1998), mechanical stress associated with breathing and locomotion (Schroter et al. 1999), redistribution of blood flow in the lungs (Bernard et al. 1996, Erickson et al. 1999) and fluctuations in alveolar pressure and pulmonary hypertension (Pascoe 1997). Several of these factors can exert severe stress on the pulmonary system to the point that the capillaries fail. Obstruction of the upper and lower airways, which decreases pulmonary ventilatory capacity, would be one of the factors considered as important in the presentation of the disease (Cook et al. 1988). In this regard, Cook (2002) proposed that the dorsal displacement of the soft palate (DDSP) interrupts the flow of air into the lungs and therefore represents a major predisposing cause of EIPH. In an equine disease that manifests as DDSP upon exercise, the horse may appear normal when examined at rest. When exercise is initiated, displacement occurs suddenly, resulting in a reduction of speed or sudden arrest of the horse’s movement. Some animals may even fall due to choking episodes, while others may experience fatal pulmonary bleeding. Moreover, trauma to the 310

This paper presents an algorithm for noninvasive estimation of alveolar pressure in mechanically ventilated patients who are spontaneously breathing. Continual monitoring of alveolar pressure is desirable to prevent ventilator-induced lung injury and to assess the intrinsic positive end-expiratory pressure (PEEPi), which is a parameter of clinical relevance in respiratory care and difficult to measure noninvasively. The algorithm is based on a physiological model of the respiratory system and, as such, it also provides insight into the respiratory mechanics of the patient under mechanical ventilation. In particular, the algorithm allows one to correctly estimate other clinical parameters of interest such as the patient's respiratory resistance and elastance, even in the presence of PEEPi.

We examined whether or not coherence between chest wall intercostal and oblique muscles changed as a function of lung volume excursion, alveolar pressure, and muscular demand. We also assessed the effects of acute expiratory threshold loading (ETL) on chest wall muscular control. A total of 15 healthy adults (7 males; average age = 28 years) completed maximum performance and ETL tasks. Chest wall surface electromyographic and kinematic recordings were made. Participants also performed a session of acute ETL. We showed that corticomuscular control of the chest wall varied as a function of lung volume excursion and muscular effort. Acute ETL had some effect on respiratory kinematics but not coherence.

Background and objective: The interrupter resistance (Rint) can be calculated from various estimates of alveolar pressure based on mouth pressure during occlusion. We compared Rint, as measured by the opening interrupter technique (Rint1), and the linear back-extrapolation method (Rint2), with the ‘gold standard’ airway resistance measured by plethysmography (Raw). Methods: The study included 32 asthmatic children and 11 children with cystic fibrosis, aged 5 to 18 years, who were categorized into non-obstructed (NObs) (n = 27) and obstructed (Obs) (n = 16) groups. Spirometry and the three different resistance measurements were performed on all children. Rint1 and Raw were assessed after a bronchodilator (BD) test in 16 and nine children, respectively, in the Obs group. Results: Raw (0.48 ± 0.20 kPa.s/L) was lower than Rint1 (1.04 ± 0.34 kPa.s/L) and Rint2 (0.63 ± 0.18 kPa.s/L) (P

Motivated by this evidence, we compare the acid-base parameters with a peculiar feature of hemodialysis patients, namely the percentage of interdialytic weight gain (IWG). This parameter is obtained by measuring the patient weight at time of the blood sampling and that at the end of the previous hemodialysis treatment. As already reported in (1), the mean IWG (±SD) is 2.8 % (±1.6). It turns out that a few percent of the analyzed samples exhibits values of IWG known to be associated with adverse outcome: only 11.2 or 4.1 %, depending on the value chosen to identify the adverse outcome [6]. Remarkably, we find a correlation (r = −0.17) between IWG and pCO2 at high level of significance (p = 0.001). More specifically, with reference to Table 1, we see that by increasing the IWG (say, from below 2 to above 4 %), there is a significant decrease of pCO2 (with p value 0.0002), while the same is not true for other blood gas analysis parameters, for which the p value does not allow us to conclude with sufficient reliability that a change occurs. We may conjecture that the decreasing of pCO2 is the early evidence of subclinical, i.e., asymptomatic, pulmonary interstitial edema, which is typically present before the hemodialysis treatment [7, 8]. Indeed, interstitial and peribronchial edema fluid may leak without interfering with respiratory exchange, as it happens in the case of left heart failure [9] and as it would seem to occur in our dataset in which, by increasing the IWG, the value of pO2 is certainly not decreasing. What is relevant here is that such interstitial edema could cause a mild degree of hyperventilation and consequently may lower the value of pCO2 in asymptomatic hemodialysis patients. This also agrees with recent experimental evidence [10]. Our aforementioned conjecture would explain both the occurrence of lower pCO2 in patients with relatively larger IWG and the frequent occurrence of respiratory Editor

Patients suffering from chronic obstructive pulmonary diseases, frequently exhibit expiratory airflow limitation. We propose a mathematical model describing the mechanical behavior of the ventilated respiratory system. This model has to simulate applied positive end-expiratory pressure (PEEP) effects during expiration, a process used by clinicians to improve airflow. The proposed model consists of a nonlinear two-compartment system. One of the compartments represents the collapsible airways and mimics its dynamic compression, the other represents the lung and chest wall compartment. For all clinical conditions tested (n=16), the mathematical model simulates the removal of expiratory airflow limitation at PEEP lower than 70–80% of intrinsic end-expiratory pressure (PEEPi), i.e. the end-expiratory alveolar pressure (PAet) without PEEP. It also shows the presence of an optimal PEEP. The optimal PEEP contributes to decrease PAet from 7.4 ± 0.9 (SD) to 5.4 ± 0.9 hPa (p < 0.0001; mild flow limitation) and from 11.8 ± 1.1 to 7.8 ± 0.7 hPa (p < 0.0001; severe flow limitation). Resistance of the collapsible compartment is decreased from 53 ± 7 to 8.2 ± 5.9 hPa.L−1.s (p < 0.0001; mild flow limitation) and from 80 ± 11 to 6.9 ± 5.4 hPa.L−1.s (p < 0.0001; severe flow limitation). This simplistic mathematical model gives a plausible explanation of the expiratory airflow limitation removal with PEEP and a rationale to the practice of PEEP application to airflow limited patients.

Mechanical support of the lungs used to preserve life or during any kind of surgery may have an adverse effect on the cardiovascular system. Usually, positive pressure in alveoli diminishes lung perfusion, venous return and cardiac output. Positive pressure during the respiratory cycle is transfered into the thoracic space. The aim of this study was to assess how synchronization of the respirator with spontaneous breathing influences the distribution of pressure and ventilation in nonhomogeneous lungs and how it should influence hemodynamics. For this purpose a multicompartmental model of respiratory system mechanics was used in the electrical analog of a respirator-lung circuit, which enabled us to simultaneously simulate ventilatory support and spontaneous breathing. Mechanical properties of the respiratory system were modeled by lumped parameters: resistances and capacitances of constant values, independent of lung volume or inspiratory flow changes. A multicompartmental model of the respiratory system enabled us to simulate lung pathology characterized by non-homogeneity of the mechanical properties of the different parts of the lungs. The results of simulations presented in the paper enable us to conclude that lung volume increase, independent of the respirator-patient breathing synchronization, may be modeled as the increase in pulmonary vascular resistance and alveolar pressure increase, dependent on respirator-patient breathing synchronization, may be averaged by esophageous balloon measurements which show intrathoracic pressure changes.

The pressure in the alveoli of the lungs, created by the elastic recoil of the lungs and respiratory muscle activity, is referred to as alveolar pressure (P a ). The extent to which tracheal pressure (P t ) approximates P a depends on the resistance to airflow offered by structures above and below the point at which tracheal pressure is measured. An understanding of the relationship among P a , P t , and upper and lower airway resistance, and how these values fluctuate during speech, could aid in interpretation and modeling of speech aerodynamics. The purpose of this study was to (a) obtain values for lower airway resistance (R law ), (b) use these R law values to estimate P a during speech, and (c) quantify the degree to which P t approximates P a during production of voiced and voiceless sounds, in comparison to inhalation. In addition, the results were discussed in terms of the degree to which the respiratory system functions as a pressure source. Tracheal pressure (obtained with tracheal puncture) and airflow were measured during sentence production in 6 subjects. Using a technique introduced in this paper, R law was determined from measures of tracheal pressure and flow obtained during a sudden change in upper airway resistance because of release of a voiceless plosive. Mean R law values ranged from 0.14 to 0.32 kPa/(l/s). Each subject's mean R law was used to derive a time-varying measure of P a during speech from continuous measures of tracheal pressure and airflow. P t was approximately 95% of P a during phonation (i.e., when the vocal folds were adducted), 75% of P a during release of the voiceless stop consonant /p/, and 55% of P a during inhalation (i.e., when the vocal folds were abducted). Therefore, the degree to which the respiratory system functioned as an ideal pressure source varied during speech. The ability to estimate P a provides a measure of the pressure produced by the respiratory system that is not influenced by laryngeal activity.

圧支持換気(pressure support ventilation, PSV)の設定圧が肺内でどのように伝播するかを調べるため,PSV中の肺胞圧を測定した。雑種成犬6頭をペントバルビタールで麻酔し,フジシステムズ製内径8.5mmのユニベントチューブを気管挿管した。犬を側臥位とし肋間筋を分け,「閉胸式カプセル法」によりカプセルを肺に接着し,その圧を肺胞圧とした。気管内圧はユニベントチューブのオクルージョンカテーテルより導出した。回路内圧,気管内圧および肺胞圧は圧トランスデューサで測定し,同時にポリグラフで記録した。PSVは呼気終末陽圧(PEEP)5cmH2O,立上がり時間0.5secで,設定圧5,10cmH2Oの2通りを検討した。回路内圧波形は設定圧に達するとプラトーとなったが,気管,肺胞圧波形ではプラトー部分はなかった。気管と肺胞の圧差は設定圧によらず極めて小さかった。正常な犬で肺内の気道抵抗は,PSV時の圧の伝播にほとんど影響を及ぼさないと考えられた。

The determinants of the shape of the pulmonary input impedance spectrum were investigated using a mathematical model based on Womersley's equations for pulsatile flow in constrained viscoelastic tubes and structural data (morphometry, elasticity, and rheology) provided for the entire cat lung by Zhuang et al. Mean distending pressures and diameters of vessels were determined from the structural data and four independent variables: cardiac output and left atrial, pleural, and alveolar pressures. Studies were performed in a control model and a model whose structure was designed to imitate that of a subject with pulmonary vascular impairment. Model simplifications were investigated. Increasing left atrial pressure or cardiac output caused passive distention of vessels that increased total blood volume and decreased vascular resistance, creating a slight spectral shift downward and to the right. Increasing pleural pressure decreased total blood volume and increased vascular resistance, creating a spectral shift upward and to the right. Increasing levels of alveolar pressure resulted in increased vascular resistance and pressures and a shift in blood volume from the capillaries to the arteries without significant change in total blood volume, creating a spectral shift that was slightly downward and to the right . Model simplification studies demonstrated that (1) all vessels distal to the tenth generation (arteries with zero distending pressure diameters < 50 μM) can be modelled as a simple resistor or (2) all vessels distal to the fourth generation can be modelled as a modified Windkessel. Results obtained from the passive studies were consistent with those obtained from normal lambs and lambs with chronically elevated pulmonary blood flow. To model a hypertensive state created by injury to the lung microvasculature, the number and size of small vessels and the compliance constants of all arteries were decreased and the viscoelastic constant was increased, which created the requisite shift to the right and upward. To better match the modulus fluctuation and negative phase angles at higher frequencies in the hypertensive animals, the development of a major reflection site between the main and branch arteries was hypothesized.

A general mathematical model for the dynamic behaviour of a single-compartment respiratory system in response to an arbitrary applied inspiratory airway pressure and arbitrary respiratory muscle activity is investigated. The model is used to compute explicit expressions for ventilation and pressure variables of clinical interest for clinician-selected and impedance-determined inputs. The outcome variables include tidal volume, end-expiratory pressure, minute ventilation, mean alveolar pressure, average pleural pressure, as well as the work performed by the ventilator and the respiratory muscles. It is also demonstrated that under suitable conditions, there is a flow reversal that can occur during inspiration.

Lung inflation was compared in isolated perfused lungs of control (C) and chronically hypoxic (CH) rats; in the latter, there is muscularization and loss of compliance in the pulmonary arterial system. During ventilation hypoxia, high alveolar pressure (Palv) elevated the pulmonary artery pressure (Ppa) less in C than in CH rats; Ppa fell during sustained inflation, rose on deflation, and after inflation hypoxic vasoconstriction was attenuated. Opposite changes took place in CH rats; Ppa often rose during inflation, fell on deflation, and after inflation hypoxic vasoconstriction was enhanced. Inflation also increased Ppa more in CH than C rats during air ventilation. Ppa/Palv relations measured during incremental inflation revealed normoxic tone in "extra-alveolar" vessels in both rat groups, which usually increased during hypoxia. In CH, but not C rats, there was also evidence for constriction in "alveolar" vessels during hypoxia. The effects of inflation were not changed by NO synthase blockade in either rat group. Pulmonary hypertensive effects of inflation in chronically hypoxic rats can be attributed to vascular remodelling.

The aim of this study was to assess the respective role of a small elevation in pulmonary capillary pressure, airway pressure, or both on alveolar capillary barrier permeability in an isolated perfused rat lung model.Four groups were studied with low or high airway pressure (LA: 10 mL/kg (tidal volume); HA: 20 mL/kg), low or high pulmonary artery pressure (LP: 9 mm Hg; HP: 12 mm Hg): LALP, HALP, LAHP, and HAHP. The lungs were ventilated and perfused ex vivo for 30 minutes. Quantification of fluorescein isothiocyanate-labeled (FITC) dextran in bronchoalveolar lavage (BAL) fluid and radiolabeled tracers assessed alveolar capillary barrier permeability.BALF FITC-dextran was similar in the three groups with either one or two low-pressure parameters (LALP, LAHP, HALP), but high amounts were found in the HAHP group (375.2 x 10(-6) mg/mL v, respectively, 21.4, 26.2, and 30 x 10(-6) mg/mL, P = .0001). These results were consistent with the albumin space and extravascular lung water: higher values only in the HAHP group statistically different from the other groups (P.002). Interalveolar pore examined with scanning electron microscopy showed an increase in diameters between LALP and HAHP (P.0001).We can conclude that elevation of either the pulmonary artery pressure from 8 to 11 mm Hg or the alveolar pressure from 10 to 15 mm Hg alone does not change the permeability of the alveolar capillary membrane; however, there is an additive effect of these pressures.

We studied respiratory system resistance by the interrupter technique (Rint) in healthy and asthmatic children, paying special attention to the effect of cheek compliance and the effects of supporting the cheeks, the influence of lung volume at which interruption was performed, the effect of direction of flow before occlusion (inspiration vs. expiration), and short-term reproducibility of this method. One hundred and thirty-two children (36 controls and 96 asthmatics) were included in the study (mean, 9.0 ± SD 3.6 years). Rint was calculated from the ratio of the alveolar pressure (estimated from mouth pressure during occlusion) to the flow prior to interruption. We observed that (1) underestimation of airway resistance due to upper airway compliance can be minimized by supporting the cheeks; Rint was significantly lower when measured without supporting the cheeks than with support of the cheeks in controls (3.9 ± 0.9 vs. 4.7 ± 1.2 cmH2O · L−1 · s, respectively) and asthmatics (5.2 ± 1.6 vs 6.9 7 plusmn; 2.0 cmH2O · L−1 · s); the quantitative differences of Rint with and without cheek support was larger in small children and in the most obstructed children; (2) performing occlusion at mid-tidal volume accurately reflected the respiratory system resistance of the whole respiratory cycle since we observed no difference in Rint when performing occlusion at different volumes during quiet respiration or at the middle of tidal volume; (3) Rint measured during expiration was higher than Rint obtained during inspiration in controls and in asthmatics; moreover, the effect of direction of flow before occlusion was greater in the small children; (4) Rint was closely correlated to height in controls (r = −0.82; P < 0.001); and (5) short-term reproducibility (at 15 min intervals) was satisfactory in controls and asthmatics (coefficients of variation were 9% and 7%, respectively). Pediatr. Pulmonol. 1997;24:78–85. © 1997 Wiley-Liss, Inc.

A bronchopulmonary vein fistula (BVF) establishes a communication between a pulmonary vein and the alveolar space presumably secondary to alveolar rupture from increase in alveolar pressure. This rare fistula allows air to move continuously from the lungs to a pulmonary vein and into the left side of the heart causing systemic air embolization which is often fatal. We describe an adult patient undergoing a second mitral valve replacement surgery in whom intra-operative transesophageal echocardiography proved crucial in diagnosing BVF by showing persistent and increased streaming of air bubbles into the left heart from the left superior pulmonary vein during each positive pressure ventilation cycle with consequent inability to de-air the heart. This allowed initiation of appropriate management. The patient eventually had a fatal outcome from multiple organ infarcts.

Study objective To compare pressure-controlled inverse ratio ventilation (PCIRV) with volume-controlled ventilation with positive end-expiratory pressure (VCV PEEP) at equal levels of end-expiratory alveolar pressure. The primary focus of the study was on pulmonary epithelial permeability. Histologic and gravimetric indicators of lung injury were also studied. Design Randomized animal study. Setting Experimental investigation at Sodersjukhuset, Stockholm, Sweden. Animals Thirty-two New Zealand white rabbits. Interventions Ventilation with PCIRV or VCV PEEP for 6 h at an end-expiratory pressure level of 5 cm H 2 O. Measurements and results Lung mechanics, heart rate, BP, and gas exchange. Measurement of pulmonary epithelial permeability by 99m Tc-DTPA lung clearance. Extravascular lung water by gravimetric analysis. Morphology by light microscopy after a perfusion fixation procedure. Mean and peak airway pressures were 12.4±4.3 and 15.9±4.5 cm H 2 O with PCIRV and 8.6±0.8 (p 2 O (p 2 was lower with PCIRV (3.2±0.6 kPa) than with VCV PEEP (4.1±0.8 kPa) (p 99m Tc-DTPA lung clearance curves were monoexponential with both PCIRV and VCV PEEP. Mean lung clearance expressed as T½ was 16±9 min with PCIRV and 107±74 min with VCV PEEP (p Conclusions The observations reported in this article imply that PCIRV causes an alteration in lung epithelial or membrane function in comparison to VCV PEEP. This functional difference is most likely caused by the large time-adjusted lung volume produced by pressure control in combination with a prolonged inspiration. It remains to be established whether this early functional effect of PCIRV is relevant with regard to structural lung injury in mechanically ventilated subjects.

We have recently demonstrated that tissue resistance increases during the early response (ER) to antigen challenge in sensitized Brown-Norway rats. The purpose of the present study was to investigate the role of the potential ER mediators 5-hydroxytryptamine (5-HT) and leukotriene D4 (LTD4) in the airway and tissue response. We sensitized the rats with ovalbumin (OA) and performed experiments on anesthetized, open-chested, mechanically ventilated [breathing frequency = 1 Hz, tidal volume = 12 ml/kg, positive end-expiratory pressure (PEEP) = 3 cmH2O] animals. We affixed alveolar capsules to the lungs to measure alveolar pressure and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw). To assess the effects of LTD4 and 5-HT, we administered the antagonists methysergide (5-HT antagonist) and MK-571 (LTD4 antagonist) before challenge. To assess lung morphometry during the ER, the lungs of four animals from each group were frozen with liquid nitrogen (PEEP = 3 cmH2O). Airway constriction was assessed by measuring the ratio of the airway lumen to the ideally relaxed airway (Abm/A*bm). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), an atelectasis index (ATI) derived by calculating the ratio of tissue to air space, and SD of the two (SD-Lm and SD-ATI). In all animals receiving OA but no antagonists, an ER was seen (RL, Rti, and Raw = 180.7 +/- 6.1, 155.4 +/- 8.2, and 223.1 +/- 14.0% of baseline, respectively). Methysergide significantly inhibited the ER (RL, Rti, and Raw = 117.0 +/- 5.9, 101.2 +/- 1.6, 133.7 +/- 10.2%, respectively), whereas MK-571 partially reduced the ER (RL, Rti, and Raw = 144.2 +/- 5.6, 132.9 +/- 5.7, and 155.5 +/- 9.2%, respectively). Abm/A*bm was significantly decreased, and SD-Lm and SD-ATI were significantly increased in animals receiving OA alone and in those receiving MK-571 before OA challenge. These data suggest that alterations in both airways and tissues contribute to the ER and that 5-HT and, to a lesser degree, LTD4 are important mediators of the ER in this rat model of extrinsic asthma.

Exercise-induced pulmonary hemorrhage (EIPH) occurs in many race horses after maximal exercise. Because of its widespread occurrence, it is considered one of the most important issues in horse racing today. Recent modeling results have shown that low alveolar pressure and high airway resistance can possibly induce EIPH. To investigate these results physically, a system capable of altering inhaled gas densities and thus the airways’ resistance was needed.

Although the lungs are a critical component of exercise performance, their response to exercise and other environmental stresses is often overlooked when evaluating pulmonary performance during high workloads. Exercise can produce capillary leakage, particularly when left atrial pressure increases related to left ventricular (LV) systolic or diastolic failure. Diastolic LV dysfunction that results in elevated left atrial pressure during exercise is particularly likely to result in pulmonary edema and capillary hemorrhage. Data from race horses, endurance athletes, and triathletes support the concept that the lungs can react to exercise and immersion stress with pulmonary edema and pulmonary hemorrhage. Immersion in water by swimmers and divers can also increase stress on pulmonary capillaries and result in pulmonary edema. Swimming-induced pulmonary edema and immersion pulmonary edema in scuba divers are well-documented events caused by the fluid shifts that occur with immersion, elevated pulmonary venous pressure during extreme exercise, and negative alveolar pressure due to inhalation resistance. Prevention strategies include avoiding extreme exercise, avoiding over hydration, and assuring that inspiratory resistance is minimized.

Almost 20 years ago, Adriaan Versprille published an editorial in this journal to explain why, in his opinion, the calculation of pulmonary vascular resistance (PVR) is meaningless [1]. The uncertainties of PVR were underscored a year later by McGregor and Sniderman in the American Journal of Cardiology [2]. Obviously, both papers failed to convince. A Medline search from 1985 to the end of 2002 reveals no less than 7,158 papers with PVR calculations. What is it that could be wrong in all this literature?

OBJECTIVE To study the effect of positive end-expiratory pressure (PEEP) on right ventricular hemodynamics and ejection fraction in patients with chronic obstructive pulmonary disease and positive alveolar pressure throughout expiration by dynamic hyperinflation (auto-PEEP). DESIGN Open, prospective, controlled trial. SETTING General intensive care unit of a community hospital. PATIENTS Ten patients sedated and paralyzed with an acute exacerbation of chronic obstructive pulmonary disease undergoing mechanical ventilation. INTERVENTIONS Insertion of a pulmonary artery catheter modified with a rapid response thermistor and a radial arterial catheter. PEEP was then increased from 0 (PEEP 0) to auto-PEEP level (PEEP = auto-PEEP) and 5 cm H2O above that (PEEP = auto-PEEP +5). MEASUREMENTS At each level of PEEP, airway pressures, flow and volume, hemodynamic variables (including right ventricular ejection fraction by thermodilution technique), and blood gas analyses were recorded. MAIN RESULTS The mean auto-PEEP was 6.6 +/- 2.8 cm H2O and the total PEEP reached was 12.2 +/- 2.4 cm H2O. The degree of lung inflation induced by PEEP averaged 145 +/- 87 mL with PEEP = auto-PEEP and 495 +/- 133 mL with PEEP = auto-PEEP + 5. The PEEP = auto-PEEP caused a right ventricular end-diastolic pressure increase, but there was no other significant hemodynamic change. With PEEP = auto-PEEP + 5, there was a significant increase in intravascular pressures; this amount of PEEP reduced cardiac output (from 4.40 +/- 1.38 L/min at PEEP 0 to 4.13 +/- 1.48 L/min; p 10% in only five cases and this group of patients had significantly lower right ventricular volumes than the group with less cardiac output variation (right ventricular end-diastolic volume: 64 +/- 9 vs. 96 +/- 26 mL/m2; right ventricular end-systolic volume: 38 +/- 6 vs. 65 +/- 21 mL/m2; p < .05) without significant difference in the other variables that were measured. Neither right ventricular ejection fraction nor right ventricle volumes changed as PEEP increased, but there were marked interpatient differences and also pronounced changes in volume between stages in individual patients. CONCLUSIONS In the study conditions, PEEP application up to values approaching auto-PEEP did not result in the impairment of right ventricular hemodynamics, while higher levels reduced cardiac output in selected patients.

Larval Ambystoma tigrinum were examined to determine their cardiovascular responses to three types of acidosis: metabolic acidosis via NH4Cl gavage; respiratory acidosis via hypercapnia; and anesthetic-induced acidosis, via triacine methanesulphonate. In addition, another group of (metabolic acidosis) animals were tested to determine the role of β-mediated catecholamine control on cardiovascular and acid-base regulation. The metabolic and respiratory acidoses produced typical amphibian responses. Anesthesia produced a significant mixed acidosis with respiratory and metabolic components. The cardiovascular responses to metabolic and respiratory acidosis were increased heart rate and pulse pressure. There were no significant changes in diastolic pressure, however, systolic pressure increased as a result of the increased pulse pressure. Animals subjected to metabolic acidosis via β-blockade with propranolol did not display the increased heart rate and pulse pressure and the acidosis was deepened and prolonged. Anesthesia resulted in a cardiac slowing and increased pulse pressure, probably explained by the Frank-Starling relationship. There was no change in diastolic pressure. Anesthetized animals had depressed blood O2 tension and elevated blood lactate.

Background Pressure-controlled (PCV) and pressure-controlled inverse ratio ventilation (PCIRV) have been proposed instead of volume-controlled conventional ratio ventilation (VC) with positive end-expiratory pressure (PEEP) for patients with adult respiratory distress syndrome (ARDS). The advantages advocated with the use of PCIRV are to decrease airway pressures and to improve gas exchange. However, most studies did not compare PCIRV and VC while keeping both the level of ventilation and end-expiratory alveolar pressure (total-PEEP) constant. Methods Nine patients with moderate to severe ARDS (lung injury score 2.83 +/- 0.18) had their lungs ventilated with VC, PCV with a conventional ratio (I:E 1:2; PC 1/2), and PCIRV (I:E 2:1 and 3:1; PC 2/1 and PC 3/1, respectively). Ventilator settings were adjusted to keep tidal volume, respiratory rate, FIo2, and total-PEEP constant in every mode. With each mode, a complete set of ventilatory, hemodynamic, and gas exchange parameters was obtained after 30 min. Results In PC 3/1, the data obtained could not be strictly compared to the other modes because total-PEEP was higher despite external-PEEP being set at zero. For the other modes (VC, PC 1/2, and PC 2/1), despite differences in peak airway pressures, no difference was noted for end-inspiratory and end-expiratory static airway pressures (which better reflect alveolar pressures) nor for lung and respiratory system compliance. Arterial oxygenation deteriorated slightly with PC 2/1 despite a higher mean airway pressure, whereas alveolar ventilation tended to be slightly, but not significantly, improved (lower PaCo2). A decrease in systolic and mean arterial pressure also was observed with PC 2/1 without other significant hemodynamic change. Conclusions In this prospective controlled study, no short-term beneficial effect of PCV or PCIRV could be demonstrated over conventional VC with PEEP in patients with ARDS.

Ventilatory flow rates with either He-O2 (heliox) or N2-O2, (nitrox) mixtures during high frequency jet ventilation (HFJV) were calculated using a mathematical model, and were measured in a physical monoalveolar model of the infant lung. A constant flow was delivered to the model (V,) drawing with it an entrained flow (Ve). When the inspiratory time (Tl) was long, a back flow (Vr) was generated that increased progressively as the alveolar pressure increased. In order to reduce Vr the reflux time (Trc), i.e., the time needed for the injected gas to reflux, was measured (Trm)and calculated (Trc) with the model: The Tr depends on both chest-lung compliance and resistance to reflux as well as on the Ve/Vd ratio. For a given setting of the ventilator, values of Trm and Trc were significantly lower with heliox than nitrox (P < 0.01), and the correlation between Trm and Trc were fair with both gases. Tidal volume (VT) was calculated when the Tl was interrupted at Tr The values of VT were significantly higher with heliox than nitrox (P < 0.05). It is concluded that the evaluation of Tr during HFJV may provide useful information for setting the ventilator. Pediatr Pulmonol. 1994; 17:183–188. © 1994 Wiley-Liss, Inc.

The development of pulmonary edema is divided in cardiogenic and non-cardiogenic. Cardiogenic edema pathogenically is caused by elevated hydrostatic pressure in the pulmonary capillaries due to left sided congestive heart failure. Non-cardiogenic pulmonary edema is categorized depending on the underlying pathogenesis in low-alveolar pressure, elevated permeability or neurogenic edema. Some important examples of causes are upper airway obstruction like in laryngeal paralysis or strangulation for low alveolar pressure, leptospirosis and ARDS for elevated permeability, and epilepsy, brain trauma and electrocution for neurogenic edema. The differentiation between cardiogenic versus non-cardiogenic genesis is not always straightforward, but most relevant, because treatment markedly differs between the two. Of further importance is the identification of the specific underlying cause in non-cardiogenic edema, not only for therapeutic but particularly for prognostic reasons. Depending on the cause the prognosis ranges from very poor to good chance of complete recovery.

We examined whether wedging a catheter (0.5 cm OD) into a subsegmental airway in dog (n = 6) or pig lungs (n = 5) and increasing pressure in the distal lung segment affected pulmonary blood flow. Dogs and pigs were anesthetized and studied in the prone position. Pulmonary blood flow was measured by injecting radiolabeled microspheres (15 microns diam) into the right atrium when airway pressure (Pao) was 0 cmH2O and pressure in the segment distal to the wedged catheter (Ps) was 0, 5, or 15 cmH2O and when Pao = Ps = 15 cmH2O. The lungs were excised, air-dried, and sectioned. Blood flow per gram dry weight normalized to cardiac output to the right or left lung, as appropriate, was calculated for the test segment, a control segment in the opposite lung corresponding anatomically to the test segment, the remainder of the lung containing the test segment (test lung), and the remainder of the lung containing the control segment (control lung). The presence of the catheter reduced blood flow in the test segment compared with that in the control segment and in the test lung. Blood flow was not affected by increasing pressure in the test segment. We conclude that, in studies designed to measure collateral ventilation in dog lungs, the presence of the wedged catheter is likely to have a greater effect on blood flow than the increase in pressure associated with measuring collateral airway resistance.

In a recent study by Tsukimoto et al. (J. Appl. Physiol. 68: 2488–2493, 1990), CO2 inhalation appeared to reduce the size of the high ventilation-perfusion ratio (VA/Q) mode commonly observed in anesthetized mechanically air-ventilated dogs. In that study, large tidal volumes (VT) were used during CO2 inhalation to preserve normocapnia. To separate the influences of CO2 and high VT on the VA/Q distribution in the present study, we examined the effect of inspired CO2 on the high VA/Q mode using eight mechanically ventilated dogs (4 given CO2, 4 controls). The VA/Q distribution was measured first with normal VT and then with increased VT. In the CO2 group at high VT, data were collected before, during, and after CO2 inhalation. With normal VT, there was no difference in the size of the high VA/Q mode between groups [10.5 +/- 3.5% (SE) of ventilation in the CO2 group, 11.8 +/- 5.2% in the control group]. Unexpectedly, the size of the high VA/Q mode decreased similarly in both groups over time, independently of the inspired PCO2, at a rate similar to the fall in cardiac output over time. The reduction in the high VA/Q mode together with a simultaneous increase in alveolar dead space (estimated by the difference between inert gas dead space and Fowler dead space) suggests that poorly perfused high VA/Q areas became unperfused over time. A possible mechanism is that elevated alveolar pressure and decreased cardiac output eliminate blood flow from corner vessels in nondependent high VA/Q regions.