Low-volume ventilation of preinjured lungs degrades lung function via stress concentration and progressive alveolar collapse.

Mechanical ventilation can cause ventilation-induced lung injury (VILI). The concept of stress concentrations suggests that surfactant dysfunction-induced microatelectases might impose injurious stresses on adjacent, open alveoli and function as germinal centers for injury propagation. The aim of the present study was to quantify the histopathological pattern of VILI progression and to test the hypothesis that injury progresses at the interface between microatelectases and ventilated lung parenchyma during low-positive end-expiratory pressure (PEEP) ventilation. Bleomycin was used to induce lung injury with microatelectases in rats. Lungs were then mechanically ventilated for up to 6 h at PEEP = 1 cmH2O and compared with bleomycin-treated group ventilated protectively with PEEP = 5 cmH2O to minimize microatelectases. Lung mechanics were measured during ventilation. Afterward, lungs were fixed at end-inspiration or end-expiration for design-based stereology. Before VILI, bleomycin challenge reduced the number of open alveoli [N(alvair,par)] by 29%. No differences between end-inspiration and end-expiration were observed. Collapsed alveoli clustered in areas with a radius of up to 56 µm. After PEEP = 5 cmH2O ventilation for 6 h, N(alvair,par) remained stable while PEEP = 1 cmH2O ventilation led to an additional loss of aerated alveoli by 26%, mainly due to collapse, with a small fraction partly edema filled. Alveolar loss strongly correlated to worsening of tissue elastance, quasistatic compliance, and inspiratory capacity. The radius of areas of collapsed alveoli increased to 94 µm, suggesting growth of the microatelectases. These data provide evidence that alveoli become unstable in neighborhood of microatelectases, which most likely occurs due to stress concentration-induced local vascular leak and surfactant dysfunction.NEW & NOTEWORTHY Low-volume mechanical ventilation in the presence of high surface tension-induced microatelectases leads to the degradation of lung mechanical function via the progressive loss of alveoli. Microatelectases grow at the interfaces of collapsed and open alveoli. Here, stress concentrations might cause injury and alveolar instability. Accumulation of small amounts of alveolar edema can be found in a fraction of partly collapsed alveoli but, in this model, alveolar flooding is not a major driver for degradation of lung mechanics.

Dynamic inflation prevents and standardized lung recruitment reverts volume loss associated with percutaneous tracheostomy during volume control ventilation: results from a Neuro-ICU population.

To determine how percutaneous tracheostomy (PT) impacts on respiratory system compliance (Crs) and end-expiratory lung volume (EELV) during volume control ventilation and to test whether a recruitment maneuver (RM) at the end of PT may reverse lung derecruitment. This is a single center, prospective, applied physiology study. 25 patients with acute brain injury who underwent PT were studied. Patients were ventilated in volume control ventilation. Electrical impedance tomography (EIT) monitoring and respiratory mechanics measurements were performed in three steps: (a) baseline, (b) after PT, and (c) after a standardized RM (10 sighs of 30 cmH2O lasting 3 s each within 1 min). End-expiratory lung impedance (EELI) was used as a surrogate of EELV. PT determined a significant EELI loss (mean reduction of 432 arbitrary units p = 0.049) leading to a reduction in Crs (55 ± 13 vs. 62 ± 13 mL/cmH2O; p < 0.001) as compared to baseline. RM was able to revert EELI loss and restore Crs (68 ± 15 vs. 55 ± 13 mL/cmH2O; p < 0.001). In a subgroup of patients (N = 8, 31%), we observed a gradual but progressive increase in EELI. In this subgroup, patients did not experience a decrease of Crs after PT as compared to patients without dynamic inflation. Dynamic inflation did not cause hemodynamic impairment nor raising of intracranial pressure. We propose a novel and explorative hyperinflation risk index (HRI) formula. Volume control ventilation did not prevent the PT-induced lung derecruitment. RM could restore the baseline lung volume and mechanics. Dynamic inflation is common during PT, it can be monitored real-time by EIT and anticipated by HRI. The presence of dynamic inflation during PT may prevent lung derecruitment.

Pericyte constriction underlies capillary derecruitment during hyperemia in the setting of arterial stenosis.

Capillary derecruitment distal to a coronary stenosis is implicated as the mechanism of reversible perfusion defect and potential myocardial ischemia during coronary hyperemia; however, the underlying mechanisms are not defined. We tested whether pericyte constriction underlies capillary derecruitment during hyperemia under conditions of stenosis. In vivo two-photon microscopy (2PM) and optical microangiography (OMAG) were used to measure hyperemia-induced changes in capillary diameter and perfusion in wild-type and pericyte-depleted mice with femoral artery stenosis. OMAG demonstrated that hyperemic challenge under stenosis produced capillary derecruitment associated with decreased RBC flux. 2PM demonstrated that hyperemia under control conditions induces 26 ± 5% of capillaries to dilate and 19 ± 3% to constrict. After stenosis, the proportion of capillaries dilating to hyperemia decreased to 14 ± 4% (P = 0.05), whereas proportion of constricting capillaries increased to 32 ± 4% (P = 0.05). Hyperemia-induced changes in capillary diameter occurred preferentially in capillary segments invested with pericytes. In a transgenic mouse model featuring partial pericyte depletion, only 14 ± 3% of capillaries constricted to hyperemic challenge after stenosis, a significant reduction from 33 ± 4% in wild-type littermate controls (P = 0.04). These results provide for the first time direct visualization of hyperemia-induced capillary derecruitment distal to arterial stenosis and demonstrate that pericyte constriction underlies this phenomenon in vivo. These results could have important therapeutic implications in the treatment of exercise-induced ischemia. NEW & NOTEWORTHY In the setting of coronary arterial stenosis, hyperemia produces a reversible perfusion defect resulting from capillary derecruitment that is believed to underlie cardiac ischemia under hyperemic conditions. We use optical microangiography and in vivo two-photon microscopy to visualize capillary derecruitment distal to a femoral arterial stenosis with cellular resolution. We demonstrate that capillary constriction in response to hyperemia in the setting of stenosis is dependent on pericytes, contractile mural cells investing the microcirculation.

PO2 oscillations induce lung injury and inflammation.

BACKGROUND: Mechanical ventilation can lead to ventilator-induced lung injury (VILI). In addition to the well-known mechanical forces of volutrauma, barotrauma, and atelectrauma, non-mechanical mechanisms have recently been discussed as contributing to the pathogenesis of VILI. One such mechanism is oscillations in partial pressure of oxygen (PO2) which originate in lung tissue in the presence of within-breath recruitment and derecruitment of alveoli. The purpose of this study was to investigate this mechanism's possible independent effects on lung tissue and inflammation in a porcine model. METHODS: To separately study the impact of PO2 oscillations on the lungs, an in vivo model was set up that allowed for generating mixed-venous PO2 oscillations by the use of veno-venous extracorporeal membrane oxygenation (vvECMO) in a state of minimal mechanical stress. While applying the identical minimal-invasive ventilator settings, 16 healthy female piglets (weight 50 ± 4 kg) were either exposed for 6 h to a constant mixed-venous hemoglobin saturation (SmvO2) of 65% (which equals a PmvO2 of 41 Torr) (control group), or an oscillating SmvO2 (intervention group) of 40-90% (which equals PmvO2 oscillations of 30-68 Torr)-while systemic normoxia in both groups was maintained. The primary endpoint of histologic lung damage was assessed by ex vivo histologic lung injury scoring (LIS), the secondary endpoint of pulmonary inflammation by qRT-PCR of lung tissue. Cytokine concentration of plasma was carried out by ELISA. A bioinformatic microarray analysis of lung samples was performed to generate hypotheses about underlying pathomechanisms. RESULTS: The LIS showed significantly more severe damage of lung tissue after exposure to PO2 oscillations compared to controls (0.53 [0.51; 0.58] vs. 0.27 [0.23; 0.28]; P = 0.0025). Likewise, a higher expression of TNF-α (P = 0.0127), IL-1ß (P = 0.0013), IL-6 (P = 0.0007), and iNOS (P = 0.0013) in lung tissue was determined after exposure to PO2 oscillations. Cytokines in plasma showed a similar trend between the groups, however, without significant differences. Results of the microarray analysis suggest that inflammatory (IL-6) and oxidative stress (NO/ROS) signaling pathways are involved in the pathology linked to PO2 oscillations. CONCLUSIONS: Artificial mixed-venous PO2 oscillations induced lung damage and pulmonary inflammation in healthy animals during lung protective ventilation. These findings suggest that PO2 oscillations represent an independent mechanism of VILI.

Alveolar Tidal recruitment/derecruitment and Overdistension During Four Levels of End-Expiratory Pressure with Protective Tidal Volume During Anesthesia in a Murine Lung-Healthy Model.

PURPOSE: We compared respiratory mechanics between the positive end-expiratory pressure of minimal respiratory system elastance (PEEPminErs) and three levels of PEEP during low-tidal-volume (6 mL/kg) ventilation in rats. METHODS: Twenty-four rats were anesthetized, paralyzed, and mechanically ventilated. Airway pressure (Paw), flow (F), and volume (V) were fitted by a linear single compartment model (LSCM) Paw(t) = Ers × V(t) + Rrs × F(t) + PEEP or a volume- and flow-dependent SCM (VFDSCM) Paw(t) = (E1 + E2 × V(t)) × V(t) + (K1 + K2 × |F(t)|) × F(t) + PEEP, where Ers and Rrs are respiratory system elastance and resistance, respectively; E1 and E2× V are volume-independent and volume-dependent Ers, respectively; and K1 and K2 × F are flow-independent and flow-dependent Rrs, respectively. Animals were ventilated for 1 h at PEEP 0 cmH2O (ZEEP); PEEPminErs; 2 cmH2O above PEEPminErs (PEEPminErs+2); or 4 cmH2O above PEEPminErs (PEEPminErs+4). Alveolar tidal recruitment/derecruitment and overdistension were assessed by the index %E2 = 100 × [(E2 × VT)/(E1 + |E2| × VT)], and alveolar stability by the slope of Ers(t). RESULTS: %E2 varied between 0 and 30% at PEEPminErs in most respiratory cycles. Alveolar Tidal recruitment/derecruitment (%E2 < 0) and overdistension (%E2 > 30) were predominant in the absence of PEEP and in PEEP levels higher than PEEPminErs, respectively. The slope of Ers(t) was different from zero in all groups besides PEEPminErs+4. CONCLUSIONS: PEEPminErs presented the best compromise between alveolar tidal recruitment/derecruitment and overdistension, during 1 h of low-VT mechanical ventilation.

Comparison of two methods of determining lung de-recruitment, using the forced oscillation technique.

Airway closure has proved to be important in a number of respiratory diseases and may be the primary functional defect in asthma. A surrogate measure of closing volume can be identified using the forced oscillation technique (FOT), by performing a deflation maneuver and examining the resultant reactance (Xrs) lung volume relationship. This study aims to determine if a slow vital capacity maneuver can be used instead of this deflation maneuver and compare it to existing more complex techniques. Three subject groups were included in the study; healthy (n = 29), asthmatic (n = 18), and COPD (n = 10) for a total of 57 subjects. Reactance lung volume curves were generated via FOT recordings during two different breathing manoeuvres (both pre and post bronchodilator). The correlation and agreement between surrogate closing volume (Volcrit) and reactance (Xrscrit) at this volume was analysed. The changes in Volcrit and Xrscrit pre and post bronchodilator were also analysed. Across all three subject groups, the two different measures of Volcrit were shown to be statistically equivalent (p > 0.05) and demonstrated a strong fit to the data (R2 = 0.49, 0.78, 0.59, for asthmatic, COPD and healthy subject groups, respectively). A bias was evident between the two measurements of Xrscrit with statistically different means (p < 0.05). However, the two measurements of Xrscrit displayed the same trends. In conclusion, we have developed an alternative technique for measuring airway closure from FOT recordings. The technique delivers equivalent and possibly more sensitive results to previous methods while being simple and easily performed by the patient.

Identification of regional overdistension, recruitment and cyclic alveolar collapse with electrical impedance tomography in an experimental ARDS model.

BACKGROUND: Information on regional ventilation distribution in mechanically ventilated patients is important to develop lung protective ventilation strategies. In the present prospective animal study, we introduce an electrical impedance tomography (EIT)-based method to classify lungs into normally ventilated, overinflated, tidally recruited/derecruited and recruited regions. METHODS: Acute respiratory distress syndrome (ARDS) was introduced with repeated bronchoalveolar lavage in ten healthy male pigs until the ratio of arterial partial pressure of oxygen and fraction of inspired oxygen (PaO2/FiO2) decreased to less than 100 mmHg and remained stable for 30 minutes. Stepwise positive end-expiratory pressure (PEEP) increments were performed from 0 cmH2O to 30 cmH2O with 3 cmH2O increase every 5 minutes. Respiratory system compliance (Crs), blood gases and hemodynamics were measured at the same time. Lung regions at end-expiration and during tidal breathing were identified in EIT images. RESULTS: Overinflated regions contain air at end-expiration but they are not or are only minimally ventilated. Recruited regions compared to reference PEEP level contain air at end-expiration of arbitrary PEEP level but not at that of reference PEEP level. Tidally recruited/derecruited regions are not represented in lung regions at end-expiration but are ventilated during tidal breathing. The results coincided with measurements of blood gases. The coefficient for correlation between the number of recruited pixels and PaO2/FiO2 was 0.89 ± 0.12 (p = 0.02). CONCLUSION: The proposed novel EIT-based method provides information on overinflation, recruitment and cyclic alveolar collapse at the bedside, which may improve the ventilation strategies used.

Efficacy of endotracheal tube clamping to prevent positive airways pressure loss and pressure behavior after reconnection: a bench study.

BACKGROUND: Endotracheal tube (ETT) clamping before disconnecting the patient from the mechanical ventilator is routinely performed in patients with acute respiratory distress syndrome (ARDS) to minimize alveolar de-recruitment. Clinical data on the effects of ETT clamping are lacking, and bench data are sparse. We aimed to evaluate the effects of three different types of clamps applied to ETTs of different sizes at different clamping moments during the respiratory cycle and in addition to assess pressure behavior following reconnection to the ventilator after a clamping maneuver. METHODS: A mechanical ventilator was connected to an ASL 5000 lung simulator using an ARDS simulated condition. Airway pressures and lung volumes were measured at three time points (5 s, 15 s and 30 s) after disconnection from the ventilator with different clamps (Klemmer, Chest-Tube and ECMO) on different ETT sizes (internal diameter of 6, 7 and 8 mm) at different clamping moments (end-expiration, end-inspiration and end-inspiration with tidal volume halved). In addition, we recorded airway pressures after reconnection to the ventilator. Pressures and volumes were compared among different clamps, different ETT-sizes and the different moments of clamp during the respiratory cycle. RESULTS: The efficacy of clamping depended on the type of clamp, the duration of clamping, the size of the ETT and the clamping moment. With an ETT ID 6 mm all clamps showed similar pressure and volume results. With an ETT ID 7 and 8 mm only the ECMO clamp was effective in maintaining stable pressure and volume in the respiratory system during disconnection at all observation times. Clamping with Klemmer and Chest-Tube at end inspiration and at end inspiration with halved tidal volume was more efficient than clamping at end expiration (p < 0.03). After reconnection to the mechanical ventilator, end-inspiratory clamping generated higher alveolar pressures as compared with end-inspiratory clamping with halved tidal volume (p < 0.001). CONCLUSIONS: ECMO was the most effective in preventing significant airway pressure and volume loss independently from tube size and clamp duration. Our findings support the use of ECMO clamp and clamping at end-expiration. ETT clamping at end-inspiration with tidal volume halved could minimize the risk of generating high alveolar pressures following reconnection to the ventilator and loss of airway pressure under PEEP.

Full-lung simulations of mechanically ventilated lungs incorporating recruitment/derecruitment dynamics.

This study developed and investigated a comprehensive multiscale computational model of a mechanically ventilated ARDS lung to elucidate the underlying mechanisms contributing to the development or prevention of VILI. This model is built upon a healthy lung model that incorporates realistic airway and alveolar geometry, tissue distensibility, and surfactant dynamics. Key features of the ARDS model include recruitment and derecruitment (RD) dynamics, alveolar tissue viscoelasticity, and surfactant deficiency. This model successfully reproduces realistic pressure-volume (PV) behavior, dynamic surface tension, and time-dependent descriptions of RD events as a function of the ventilation scenario. Simulations of Time-Controlled Adaptive Ventilation (TCAV) modes, with short and long durations of exhalation (T Low - and T Low +, respectively), reveal a higher incidence of RD for T Low + despite reduced surface tensions due to interfacial compression. This finding aligns with experimental evidence emphasizing the critical role of timing in protective ventilation strategies. Quantitative analysis of energy dissipation indicates that while alveolar recruitment contributes only a small fraction of total energy dissipation, its spatial concentration and brief duration may significantly contribute to VILI progression due to its focal nature and higher intensity. Leveraging the computational framework, the model may be extended to facilitate the development of personalized protective ventilation strategies to enhance patient outcomes. As such, this computational modeling approach offers valuable insights into the complex dynamics of VILI that may guide the optimization of ventilation strategies in ARDS management.

Protective ventilation in a pig model of acute lung injury: timing is as important as pressure.

Ventilator-induced lung injury (VILI) is a significant risk for patients with acute respiratory distress syndrome (ARDS). Management of the patient with ARDS is currently dominated by the use of low tidal volume mechanical ventilation, the presumption being that this mitigates overdistension (OD) injury to the remaining normal lung tissue. Evidence exists, however, that it may be more important to avoid cyclic recruitment and derecruitment (RD) of lung units, although the relative roles of OD and RD in VILI remain unclear. Forty pigs had a heterogeneous lung injury induced by Tween instillation and were randomized into four groups (n = 10 each) with higher (↑) or lower (↓) levels of OD and/or RD imposed using airway pressure release ventilation (APRV). OD was increased by setting inspiratory airway pressure to 40 cmH2O and lessened with 28 cmH2O. RD was attenuated using a short duration of expiration (∼0.45 s) and increased with a longer duration (∼1.0 s). All groups developed mild ARDS following injury. RD ↑ OD↑ caused the greatest degree of lung injury as determined by [Formula: see text]/[Formula: see text] ratio (226.1 ± 41.4 mmHg). RD ↑ OD↓ ([Formula: see text]/[Formula: see text]= 333.9 ± 33.1 mmHg) and RD ↓ OD↑ ([Formula: see text]/[Formula: see text] = 377.4 ± 43.2 mmHg) were both moderately injurious, whereas RD ↓ OD↓ ([Formula: see text]/[Formula: see text] = 472.3 ± 22.2 mmHg; P < 0.05) was least injurious. Both tidal volume and driving pressure were essentially identical in the RD ↑ OD↓ and RD ↓ OD↑ groups. We, therefore, conclude that considerations of expiratory time may be at least as important as pressure for safely ventilating the injured lung.NEW & NOTEWORTHY In a large animal model of ARDS, recruitment/derecruitment caused greater VILI than overdistension, whereas both mechanisms together caused severe lung damage. These findings suggest that eliminating cyclic recruitment and derecruitment during mechanical ventilation should be a preeminent management goal for the patient with ARDS. The airway pressure release ventilation (APRV) mode of mechanical ventilation can achieve this if delivered with an expiratory duration (TLow) that is brief enough to prevent derecruitment at end expiration.

A Comparison of Motor Unit Control Strategies between Two Different Isometric Tasks.

BACKGROUND: This study examined the motor unit (MU) control strategies for non-fatiguing isometric elbow flexion tasks at 40% and 70% maximal voluntary isometric contraction. METHODS: Nineteen healthy individuals performed two submaximal tasks with similar torque levels: contracting against an immovable object (force task), and maintaining the elbow joint angle against an external load (position task). Surface electromyographic (EMG) signals were collected from the agonist and antagonist muscles. The signals from the agonist were decomposed into individual action potential trains. The linear regression analysis was used to examine the MU recruitment threshold (RT) versus mean firing rates (MFR), and RT versus derecruitment threshold (DT) relationships. RESULTS: Both agonist and antagonist muscles' EMG amplitudes did not differ between two tasks. The linear slopes of the MU RT versus MFR and RT versus DT relationships during the position task were more negative (p = 0.010) and more positive (p = 0.023), respectively, when compared to the force task. CONCLUSIONS: To produce a similar force output, the position task may rely less on the recruitment of relatively high-threshold MUs. Additionally, as the force output decreases, MUs tend to derecruit at a higher force level during the position task.

Atelectrauma Versus Volutrauma: A Tale of Two Time-Constants.

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 role of pericytes in hyperemia-induced capillary de-recruitment following stenosis.

PURPOSE: The microvascular capillary network is ensheathed by cells called pericytes - a heterogeneous population of mural cells derived from multiple lineages. Pericytes play a multifaceted role in the body, including in vascular structure and permeability, regulation of local blood flow, immune and wound healing functions, induction of angiogenesis, and generation of various progenitor cells. Here, we consider the role of pericytes in capillary de-recruitment, a pathophysiologic phenomenon that is observed following hyperemic stimuli in the presence of a stenosis and attenuates the hyperemic response. RECENT FINDINGS: We discuss recent observations that conclusively demonstrate pericytes to be the cellular structures that contract in response to hyperemic stimuli when an upstream arterial stenosis is present. This response constricts capillaries, which is likely aimed at maintaining capillary hydrostatic pressure, an important factor in tissue homeostasis. Nonetheless, the ensuing attenuation of the hyperemic response can lead to a decrease in energy supply and negatively impact tissue health. SUMMARY: Therapeutics aimed at preventing pericyte-mediated capillary de-recruitment may prove beneficial in conditions such as coronary stenosis and peripheral arterial disease by reducing restriction in hyperemic flow. Identification of the pericyte subtypes involved in this de-recruitment and the underlying molecular mechanisms regulating this process will greatly assist this purpose.

Derecruitment volume assessment derived from pressure-impedance curves with electrical impedance tomography in experimental acute lung injury.

OBJECTIVE: To investigate the accuracy of derecruitment volume (VDER) assessed by pressure-impedance (P-I) curves derived from electrical impedance tomography (EIT). METHODS: Six pigs with acute lung injury received decremental positive end-expiratory pressure (PEEP) from 15 to 0 in steps of 5 cmH2O. At the end of each PEEP level, the pressure-volume (P-V) curves were plotted using the low constant flow method and release maneuvers to calculate the VDER between the PEEP of setting levels and 0 cmH2O (VDER-PV). The VDER derived from P-I curves that were recorded simultaneously using EIT was the difference in impedance at the same pressure multiplied by the ratio of tidal volume and corresponding tidal impedance (VDER-PI). The regional P-I curves obtained by EIT were used to estimate VDER in the dependent and nondependent lung. RESULTS: The global lung VDER-PV and VDER-PI showed close correlations (r = 0.948, P<0.001); the mean difference was 48 mL with limits of agreement of -133 to 229 mL. Lung derecruitment extended into the whole process of decremental PEEP levels but was unevenly distributed in different lung regions. CONCLUSIONS: P-I curves derived from EIT can assess VDER and provide a promising method to estimate regional lung derecruitment at the bedside.

Early onset of airway derecruitment assessed using the forced oscillation technique in subjects with asthma.

Derecruitment of air spaces in the lung occurs when airways close during exhalation and is related to ventilation heterogeneity and symptoms in asthma. The forced oscillation technique has been used to identify surrogate measures of airway closure via the reactance (Xrs) versus lung volume relationship. This study used a new algorithm to identify derecruitment from the Xrs versus lung volume relationship from a slow vital capacity maneuver. We aimed to compare two derecruitment markers on the Xrs versus volume curve, the onset reduction of Xrs (DR1vol) and the onset of more rapid reduction of Xrs (DR2vol), between control and asthmatic subjects. We hypothesized that the onset of DR1vol and DR2vol occurred at higher lung volume in asthmatic subjects. DR1vol and DR2vol were measured in 18 subjects with asthma and 18 healthy controls, and their relationships with age and height were examined using linear regression. In the control group, DR1vol and DR2vol increased with age (r2 = 0.68, P < 0.001 and r2 = 0.71, P < 0.001, respectively). DR1vol and DR2vol in subjects with asthma [76.58% of total lung capacity (TLC) and 56.79%TLC, respectively] were at higher lung volume compared with control subjects (46.1 and 37.69%TLC, respectively) (P < 0.001). DR2vol correlated with predicted values of closing capacity (r = 0.94, P < 0.001). This study demonstrates that derecruitment occurs at two points along the Xrs-volume relationship. Both derecruitment points occurred at significantly higher lung volumes in subjects with asthma compared with healthy control subjects. This technique offers a novel way to measure the effects of changes in airways/lung mechanics. NEW & NOTEWORTHY This study demonstrates that the forced oscillation technique can be used to identify two lung volume points where lung derecruitment occurs: 1) where derecruitment is initiated and 2) where onset of rapid derecruitment commences. Measurements of derecruitment increase with age. The onset of rapid derecruitment was highly correlated with predicted closing capacity. Also, the initiation and rate of derecruitment are significantly altered in subjects with asthma.

Ventilator-induced lung injury and lung mechanics.

Mechanical ventilation applies physical stresses to the tissues of the lung and thus may give rise to ventilator-induced lung injury (VILI), particular in patients with acute respiratory distress syndrome (ARDS). The most dire consequences of VILI result from injury to the blood-gas barrier. This allows plasma-derived fluid and proteins to leak into the airspaces where they flood some alveolar regions, while interfering with the functioning of pulmonary surfactant in those regions that remain open. These effects are reflected in commensurately increased values of dynamic lung elastance (EL ), a quantity that in principle is readily measured at the bedside. Recent mathematical/computational modeling studies have shown that the way in which EL varies as a function of both time and positive end-expiratory pressure (PEEP) reflects the nature and degree of lung injury, and can even be used to infer the separate contributions of volutrauma and atelectrauma to VILI. Interrogating such models for minimally injurious regimens of mechanical ventilation that apply to a particular lung may thus lead to personalized approaches to the ventilatory management of ARDS.

Fatal derecruitment of occluded left anterior descending collaterals after left circumflex revascularization.

Coronary arteries are not definitely functionally terminal arteries, as previously thought; indeed, they are linked and interconnected by a rich network of collaterals. Chronic total occlusions (CTOs) represent a subset of frequent lesions encountered in everyday catheterization laboratory practice, generally associated with a developed system of collateral connections. These latter have the capacity to prevent myocardial necrosis and may even uphold metabolic supply to the ischemic territory to maintain its contractile capacity. Authors have reported a rapid and progressive reduction of collateral function and their decline after antegrade flow restoration, resulting in higher myocardial susceptibility to ischemia in the CTO territory. Here, we report the case of a fatal derecruitment of collaterals for a left anterior descending CTO not reopened, after left circumflex subocclusion revascularization.

Lung volume changes during cleaning of closed endotracheal suction catheters: a randomized crossover study using electrical impedance tomography.

BACKGROUND: Airway suctioning in mechanically ventilated patients is required to maintain airway patency. Closed suction catheters (CSCs) minimize lung volume loss during suctioning but require cleaning post-suction. Despite their widespread use, there is no published evidence examining lung volumes during CSC cleaning. The study objectives were to quantify lung volume changes during CSC cleaning and to determine whether these changes were preventable using a CSC with a valve in situ between the airway and catheter cleaning chamber. METHODS: This prospective randomized crossover study was conducted in a metropolitan tertiary ICU. Ten patients mechanically ventilated via volume-controlled synchronized intermittent mandatory ventilation (SIMV-VC) and requiring manual hyperinflation (MHI) were included in this study. CSC cleaning was performed using 2 different brands of CSC (one with a valve [Ballard Trach Care 72, Kimberly-Clark, Roswell, Georgia] and one without [Portex Steri-Cath DL, Smiths Medical, Dublin, Ohio]). The maneuvers were performed during both SIMV-VC and MHI. Lung volume change was measured via impedance change using electrical impedance tomography. A mixed model was used to compare the estimated means. RESULTS: During cleaning of the valveless CSC, significant decreases in lung impedance occurred during MHI (-2563 impedance units, 95% CI 2213-2913, P < .001), and significant increases in lung impedance occurred during SIMV (762 impedance units, 95% CI 452-1072, P < .001). In contrast, cleaning of the CSC with a valve in situ resulted in non-significant lung volume changes and maintenance of normal ventilation during MHI and SIMV-VC, respectively (188 impedance units, 95% CI -136 to 511, P = .22; and 22 impedance units, 95% CI -342 to 299, P = .89). CONCLUSIONS: When there is no valve between the airway and suction catheter, cleaning of the CSC results in significant derangements in lung volume. Therefore, the presence of such a valve should be considered essential in preserving lung volumes and uninterrupted ventilation in mechanically ventilated patients.

Motor unit firing rates during spasms in thenar muscles of spinal cord injured subjects.

Involuntary contractions of paralyzed muscles (spasms) commonly disrupt daily activities and rehabilitation after human spinal cord injury (SCI). Our aim was to examine the recruitment, firing rate modulation, and derecruitment of motor units that underlie spasms of thenar muscles after cervical SCI. Intramuscular electromyographic activity (EMG), surface EMG, and force were recorded during thenar muscle spasms that occurred spontaneously or that were triggered by movement of a shoulder or leg. Most spasms were submaximal (mean: 39%, SD: 33 of the force evoked by median nerve stimulation at 50 Hz) with strong relationships between EMG and force (R (2) > 0.69). Unit recruitment occurred over a wide force range (0.2-103% of 50 Hz force). Significant unit rate modulation occurred during spasms (frequency at 25% maximal force: 8.8 Hz, 3.3 SD; at maximal force: 16.1 Hz, 4.1 SD). Mean recruitment frequency (7.1 Hz, 3.2 SD) was significantly higher than derecruitment frequency (5.4 Hz, 2.4 SD). Coactive unit pairs that fired for more than 4 s showed high (R (2) > 0.7, n = 4) or low (R (2):0.3-0.7, n = 12) rate-rate correlations, and derecruitment reversals (21 pairs, 29%). Later recruited units had higher or lower maximal firing rates than lower threshold units. These discrepant data show that coactive motoneurons are drive both by common inputs and by synaptic inputs from different sources during muscle spasms. Further, thenar motoneurons can still fire at high rates in response to various peripheral inputs after SCI, supporting the idea that low maximal voluntary firing rates and forces in thenar muscles result from reduced descending drive.