Ventilation patterns, surfactant and lung injury.
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Humans↗
Biomedical subjects
B Jonson
Publications and source records attributed to B Jonson.
Surfactant dysfunction makes lungs vulnerable to repetitive collapse and reexpansion.
Reexpansion of collapsed lung creates intrapulmonary shear forces. In an earlier study we showed that application of a negative end-expiratory airway pressure (NEEP) to normal rabbit lungs in vivo produced tidal collapse and reexpansion with transient changes in compliance and gas exchange but no histologic damage. In the present study we examined NEEP in a model of surfactant perturbation produced by an inhaled aerosol of 2% and 5% dioctyl sodium sulfosuccinate (DOSS). DOSS increased alveolocapillary permeability without affecting compliance or oxygenation. Repeated collapse and reexpansion (RECOREX), caused by NEEP for 3 h was compared with ventilation with positive-end expiratory pressure (PEEP). Groups ventilated with PEEP maintained normal lung mechanics and morphology even if pretreated with DOSS. NEEP disturbed lung mechanics and gas exchange with persistent dose-related histologic damage in animals pretreated with DOSS. Lungs subjected to NEEP without DOSS had normal morphology. We conclude that perturbation of the surfactant system makes lungs vulnerable to injury by RECOREX. The combination of DOSS and NEEP might lead to leakage of plasma proteins into alveoli, causing inactivation of surfactants and increased shear forces with resulting lung damage. Similar mechanisms may accelerate lung damage in the respiratory distress syndrome.
Animals↗
Pressure-volume curves in acute respiratory failure: automated low flow inflation versus occlusion.
Pressure-volume (P-V) curves of the respiratory system allow determination of compliance and lower and upper inflection points (LIP and UIP, respectively). To minimize lung trauma in mechanical ventilation the tidal volume should be limited to the P-V range between LIP and UIP. An automated low flow inflation (ALFI) technique, using a computer-controlled Servo Ventilator 900C, was compared with a more conventional technique using a series of about 20 different inflated volumes (Pst-V curve). The pressure in the distal lung (Pdist) was calculated by subtraction of resistive pressure drop in connecting tubes and airways. Compliance (Cdist), Pdist(LIP), and Pdist(UIP) were derived from the Pdist-V curve and compared with Cst, Pst(LIP), and Pst(UIP) derived from the Pst-V curve. Nineteen sedated, paralyzed patients (10 with ARDS and 9 with ARF) were studied. We found: Cdist = 2.3 + 0.98 x Cst ml/cm H2O (r = 0.98); Pdist(LIP) = 0.013 + 1.09 x Pst(LIP) cm H2O (r = 0.96). In patients with ARDS: Pdist(UIP) = 4.71 + 0.84 x Pst(UIP) cm H2O (r = 0.94). In ARF, we found differences in UIP between the methods, but discrepancies occurred above tidal volumes and had little practical importance. They may reflect that Pdist comprises dynamic phenomena contributing to pressure in the distal lung at large volumes. Compliance, but not LIP and UIP, could be accurately determined without subtraction of resistive pressure from the pressure measured in the ventilator. We conclude that ALFI, which is fully automated and needing no ventilator disconnection, gives useful clinical information.
Acute Disease↗
Additive nature of distension and surfactant perturbation on alveolocapillary permeability.
The aim of this study was to determine whether the effects of alveolar distention and surfactant dysfunction on alveolocapillary barrier function are different and additive. Pulmonary clearance of aerosolized technetium-99m-labelled human serum albumin (99mTc-HSA) was used to characterize barrier function after perturbing the surfactant system with the detergent dioctyl sodium sulphosuccinate either singly or in combination with large tidal volume ventilation (LTVV). Clearance was measured for 3 h (Experimental ventilation) in four groups (n = 6 each) of rabbits: 1) Controls; 2) Detergent; 3) LTVV; and 4) Detergent + LTVV. Restoration of clearance (Recovery) was studied for 3 h under conventional ventilation. The half-life of clearance (t 1/2) decreased during LTVV (305 min) compared to 1,055 min in Controls. Detergent induced a biexponential clearance with slow (t 1/2S) and fast (t 1/2F) half-lives of 670 and 15.4 min, respectively. The fast fraction (fF) was 0.20. Clearance in the Detergent + LTVV group was also biexponential. The t 1/2F and fF were similar to the Detergent group. The t 1/2S was similar to the LTVV group. The fF in this group increased to 0.36 during Recovery (p < 0.01 versus Detergent group and p < 0.05 versus Experimental ventilation). The diverse kinetics of clearance during large tidal volume ventilation and surfactant dysfunction suggest the presence of different mechanisms affecting the barrier. The mechanisms have additive characteristics, which superimpose to produce lung injury.
Aerosols↗
Pulmonary perfusion and density gradients in healthy volunteers.
UNLABELLED: The goal of this study was to measure regional pulmonary perfusion using SPECT and transmission tomography for attenuation correction and density measurements. METHODS: Regional pulmonary perfusion was studied after intravenous injection of radiolabeled particles in 10 supine healthy volunteers using SPECT. Transmission tomography was used to correct for attenuation, measure lung density and delineate the lungs. The effects of attenuation correction on pulmonary perfusion gradients were investigated. RESULTS: In perfusion measurements not corrected for attenuation, we found significant perfusion gradients in the direction of gravity but also significant gradients at isogravitational level. After correction for attenuation, the gravitational gradient was significantly greater than before correction, and gradients at isogravitational level were no longer observed. Perfusion in the ventral lung zone was half of that in the dorsal lung zone. Mean lung density was 0.28 +/- 0.03 g/ml, and density showed a significant increase in the direction of gravity and at isogravitational level. CONCLUSION: We found that SPECT perfusion studies of the lung not corrected for attenuation gave a false impression of nongravitational gradients and underestimate the gradient that is gravity-dependent. Transmission tomography, used for attenuation correction, also quantifies lung density and shows gravity dependent and nondependent density gradients.
Female↗
Single-neutron states in 133Sn.
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Journal Article↗
Respiratory mechanics in rabbits ventilated with different tidal volumes.
Respiratory mechanics was studied in 11 rabbits at tidal volumes (VT) of 6.7, 10, and 20 ml/kg. Flow interruptions were performed during the full respiratory cycle. The viscoelastic pressure (Pve) was measured as the dynamic elastic pressure (Pel(dyn)) after flow cessation minus the static elastic pressure (Pel(st)). Static elastic and viscoelastic parameters were determined with numerical technique. Static hysteresis was minimal even at large VT. The Pel(st)-V curve was linear at small VT and in 6 animals at moderate VT. In 5 animals at moderate VT and in all animals at large VT, a linear segment with constant compliance was followed by a segment with decreasing compliance. The Pve-V curve could be described with a linear model only at small VT. A non-linear model was needed at increased VT. Compliance increased with VT. Both static and viscoelastic behaviours were linear up to larger volume ranges at large VT compared to moderate VT.
Animals↗
Study of the unbound nucleus 11N by elastic resonance scattering.
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Journal Article↗
Respiratory mechanics in patients ventilated for critical lung disease.
Respiratory mechanics, using flow interruption, was previously studied during the complete breath in healthy ventilated man, numerical techniques relieving constraints regarding flow pattern. The classical linear model of non-Newtonian behaviour was found to be valid. The present study was extended to subjects with critical lung disease. Subjects with acute lung injury (ALI; n = 2), acute respiratory distress syndrome (ARDS; n = 4), and chronic obstructive pulmonary disease (COPD; n = 3) were studied with and without positive end-expiratory pressure (PEEP). Functional residual capacity (FRC) was measured with sulphur hexafluoride (SF6) wash-out. The static pressure-volume (P-V) curve was linear at zero end-expiratory pressure (ZEEP), but nonlinear at PEEP. Its hysteresis was nonsignificant. In ALI/ARDS, PEEP increased lung volume by distension and recruitment, but only by distension in COPD. In ALI/ARDS, resistance was increased, at ZEEP. In COPD, resistance became extremely high during expiration at ZEEP. In ALI/ARDS at ZEEP, non-Newtonian behaviour, representing tissue stress relaxation and pendel-luft, complied with the classical linear model. At PEEP, the non-Newtonian compliance became volume-dependent to an extent correlated to the nonlinearity of the static P-V curve. In COPD, non-Newtonian behaviour was adequately explained only with a model with different inspiratory and expiratory behaviour. The classical model of the respiratory system is valid in ALI/ARDS at ZEEP. More advanced models are needed at PEEP and in COPD.
Adult↗
Study of the Unstable Nucleus 10Li in Stripping Reactions of the Radioactive Projectiles 11Be and 11Li.
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Journal Article↗
Healthy lungs tolerate repetitive collapse and reopening during short periods of mechanical ventilation.
The possible occurrence of lung damage if alveolar units are allowed to collapse and reopen breath by breath during mechanical ventilation with normal tidal volumes was investigated. Anaesthetised, paralysed, open chest rabbits were subjected to either intrathoracic negative (NEEP; n = 6) or positive (PEEP; n = 6) end-expiratory pressure during volume controlled mechanical ventilation. Both experimental settings were preceded by a 30 min control period and followed by a 30 min recovery period during which a PEEP of 0.2 kPa was maintained. Pao2 and pulmonary compliance deteriorated significantly in the NEEP group during the experimental period and compared to ventilation with PEEP. Partial restoration of lung mechanics and blood gases was achieved during the recovery period. After an alveolar recruitment manoeuvre, this recovery was complete. Lung clearance studied by depositing an aerosol of technetium-99m-labelled diethylenetriamine pentaacetate (99mTc-DTPA) in the alveoli, was significantly faster during ventilation with NEEP compared to the PEEP group (P = 0.0002) as well as the control period (P = 0.0029). It did not recover completely during the recovery period but remained significantly faster. Light microscopic histology was normal in both groups with no evidence of inflammation or epithelial disruption. We conclude that previously healthy rabbit lungs show only a transient disturbance of lung mechanics and blood gases with repetitive collapse and re-expansion. The integrity of the alveolar microstructure is preserved. The disturbance in the alveolo-capillary permeability persists and may indicate surfactant related alveolo-capillary barrier dysfunction.
Animals↗
Dynamics of carbon dioxide elimination following ventilator resetting.
BACKGROUND: Carbon dioxide elimination (VCO2) at steady state corresponds to the metabolic rate. A change in tidal ventilation will lead to a transient response in VCO2 if other determinants of VCO2 are constant. This principle may be applied in the critical care unit to reset ventilators. OBJECTIVE: To define and characterize the transient response of VCO2 to a well-defined change in ventilation. METHODS: Forty-four patients in stable condition receiving volume-controlled mechanical ventilation had trend recordings of ventilator pressures, flow, volumes, VCO2, and end-tidal CO2 (ETCO2) for 20 min. At time t0, the minute ventilation was either increased (n = 22) or decreased (n = 22) by 10% after which these parameters were monitored over 30 min. Blood gas values were measured 5 and 20 min after the change in ventilation and the dead space fractions were computed using the single breath-CO2 test. DATA ANALYSIS: The first ten breaths (till t1) after a change in ventilation were excluded. The time constant (tau) of the relative change in VCO2 (delta VCO2) was calculated by fitting exponential regressions to delta VCO2 for periods up to 20 min after t1. RESULTS: The delta VCO2 at t1 was proportional to the relative change in tidal volume (delta VT). The proportionality decreased gradually during 20 min. The proportionality of the relative change in ETCO2 (delta ETCO2) or PaCO2 (delta PaCO2) with delta VT was minimal at t1 and increased during the 20 min. tau increased progressively when calculated over longer periods (p < 0.001). tau was similar in the groups with increased and decreased ventilation up to 5 min, after which it was longer in the group with decreased ventilation (p < 0.05). The delta PaCO2 after 20 min correlated best with delta VCO2 at t1 (r = -0.8) and with delta ETCO2 at the end of 20 min (r = 0.8). CONCLUSIONS: Noninvasively monitored VCO2 provides an instantaneous indication of the change in alveolar ventilation in well-sedated, mechanically ventilated patients in stable condition without significant cardiopulmonary disease.
Adult↗
Different kinetics of lung clearance of technetium-99m labelled diethylene triamine penta-acetic acid in patients with sarcoidosis and smokers.
The rate of clearance from the lungs of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (99mTc-DTPA) is often increased in interstitial lung disease as well as in smoking. In smokers a bi-exponential clearance course of 99mTc-DTPA when measured over 3 h has previously been shown. This study was performed to compare the kinetics of clearance of 99mTc-DTPA, measured for 3 h, in sarcoid patients and healthy smokers. Forty-one never-smoking patients with sarcoidosis and radiological signs of intrathoracic disease were studied. The results were compared with those of 16 healthy current smokers and of 14 healthy never-smokers reported previously. A mono-exponential clearance equation described the clearance in 22 of the sarcoid patients and all normal never-smokers, but with a shorter average tracer half-life in the patients (P < 0.05). In 19 patients and all smokers a bi-exponential equation gave a significantly better curve fit. The rate of clearance of the slow component was higher in patients with sarcoidosis than in smokers (P < 0.05). The fraction of the tracer cleared by the fast clearance component was smaller in patients with sarcoidosis than in smokers (P < 0.01). Differences in kinetics of clearance of 99mTc-DTPA in sarcoidosis and smoking could thus be demonstrated, suggesting that the abnormal clearance is caused by diverging pathophysiological mechanisms.
Adult↗
Selective deposition of inhaled aerosols to mechanically ventilated rabbits.
We have studied selective deposition of tracer aerosols to specific sites in airways and peripheral regions of the rabbit lung by varying droplet size and breathing pattern. The different breathing patterns were controlled by a Servo Ventilator 900C and different droplet sizes (polydisperse) were generated by an air jet nebulizer (MA2) using two types of impactor vessels (MMD 2.3 and 4.1 microns). Three tracer aerosols were evaluated; Evans blue dye, 99mTc-DTPA and monodisperse fluorescent polylatex spheres (PLS). When we combined large droplets with "rapid-shallow" breathing (central deposition mode, CDM), 30% of the aerosol was deposited in the central airways. When small droplets were combined with "deep-slow" breathing (peripheral deposition mode, PDM) 60% was deposited in the peripheral part of the lung. The different detection techniques showed similar results but gave complementary information. Since detection of the radiolabelled aerosol was more sensitive than the other methods, less aerosol could be given allowing a more precise evaluation of the deposition, both from the macro autoradiographic images as well as from the well counter measurements. In order to investigate how far into the lung periphery the aerosol could be detected, we used PSL microspheres. PLS could be detected in the alveolar region by a fluorescent light microscope. However, a complete selectivity can not be obtained by aerosol delivery. The different technique used to reach selective deposition, showed that it is only possible to deposit the aerosol either more to the central or more to the peripheral parts of the respiratory tract in small subjects.
Administration, Inhalation↗
Airway and body surface sensors for triggering in neonatal ventilation.
Failure of neonatal patient triggered ventilation may reflect a delay in delivery of flow relative to the inspiratory effort of the infant. Transmission of diaphragmatic contraction to the sensor site (patient delay) and further transmission to and within the sensing device (device delay) both contribute to the delay in triggering. Patient and device delays were studied for different sensing systems in 36 infants, 24 of whom were intubated. Device delay was long (> 40 ms) with a conventional apnoea monitor compared with sensors placed at the airway opening (2 ms), the inspiratory (12 ms) and expiratory (3 ms) pressure transducers of the ventilator, the Graseby capsule (8 ms), strain gauges (3 ms) and oesophageal pressure (6 ms). In near normal infants, the sum of patient and device delays for the latter sensors was less than 20 ms and a minor component of the total delay. However, in severe lung disease the total delay may be more than 100 ms even for airway sensors.
Airway Resistance↗
Effect of detergent on alveolar particle clearance due to large tidal ventilation.
BACKGROUND: It has recently been shown that large tidal volume ventilation accelerates the alveolar clearance of insoluble particles and this may be related to accelerated surfactant evacuation from the alveolus into the airway. The aim of this study was to investigate if the effect of large tidal volume ventilation is modified in an experimental model of surfactant dysfunction. METHODS: Fluorescent latex particles of 0.63 microns diameter were administered in aerosol form to 30 rabbits during anaesthesia with thiopentone and mechanical ventilation. Six animals were killed immediately after aerosol administration in order to show the initial deposition of particles. Twenty four animals were divided into two groups and ventilated for three hours with either large tidal volume (mean tidal volume 30 ml/kg) or conventional ventilation (mean tidal volume 12.5 ml/kg). Six rabbits in each of the two groups were administered either the synthetic detergent dioctyl sodium sulphosuccinate in aerosol form or aerosolised vehicle. After the period of experimental ventilation the lungs were removed and dried in the expanded state. Particles in the alveolar region were counted with fluorescent microscopy in sections of the lung. RESULTS: Compared with the baseline group (mean (SD) 24.8 (9.9)) the count of residual alveolar particles was lower after large tidal volume ventilation in the absence of detergent aerosol (13.2 (6.5)). Particle count after large tidal volume ventilation and detergent treatment (23.3 (6.4)) was similar to that in the baseline group and to that in the groups exposed to conventional ventilation. CONCLUSIONS: The increase in alveolar clearance of insoluble particles caused by large tidal volume ventilation is inhibited by detergent aerosol. This might be due to reduced stability of the surfactant film after detergent aerosol.
Aerosols↗
Tidal volume and alveolar clearance of insoluble particles.
We studied the effect of 3 h of large tidal volume ventilation on alveolar clearance of 0.63-micron fluorescent latex particles in rabbits during pentobarbital anesthesia. After particle deposition, six animals were killed as controls, six were subjected to large tidal volume ventilation with a peak pressure of 27 cmH2O, and six were subjected to conventional ventilation with a peak pressure of 11 cmH2O. Mean tidal volumes were 30.2 +/- 6.1 and 8.4 +/- 1.6 ml/kg in the large tidal volume and conventional groups, respectively. End-expiratory pressure was 2 cmH2O in all groups. Compliance decreased only after large tidal ventilation (P = 0.0036). Compared with controls the conventional ventilation group showed no alveolar clearance, but more particles were clustered within macrophages (P = 0.01). Compared with other groups the large tidal volume group had fewer alveolar particles (P = 0.0005), most of which were single particles. Accordingly, large tidal volumes enhance alveolar particle clearance, which is possibly related to distension-related evacuation of surfactant to proximal airways. Clearance may be due to accelerated motion of the particle-loaded macrophage in response to the fast film motion. Alternatively, single particles embedded in the surfactant film may be dragged by the fast-moving film toward the airways.
Animals↗
Relationships between regional ventilation and vascular and extravascular volume in supine humans.
With the use of positron emission tomography, alveolar ventilation (VA), lung density, and pulmonary blood volume (VB) were measured regionally in eight nonsmokers in the supine posture and one nonsmoker in the prone posture during quiet breathing in a transaxial thoracic section at midheart level. Regional values of alveolar volume (VA) and extravascular tissue volume (VEV) were derived from the inherent relationships between different compartments in the lung. Ratios proportional to gas volume (VA/VEV) and ventilation (VA/VEV) per alveolar unit, respectively, were calculated. No differences between right and left lung were found. Variations in the vertical direction could explain approximately 65% of the total within-group variation in VA, VB, and ln (VA), whereas the corresponding value for horizontal variation was only 3-9% (right lung, supine subjects). Similar gravitational gradients were found in the single prone subject. There was a significant linear correlation between VA and ln (VA). When VA and VA are related to a given number of alveolar units (VEV), the data are consistent with a linear relationship between VA/VEV and VA/VEV, indicating that ventilation might be explained by the elastic properties of lung tissue according to Salazar and Knowles (J. Appl. Physiol. 19: 97-104, 1964). Regional VB was closely associated with the gradient of regional alveolar volume (VA/VEV) (by virtue of weight of blood and competition for space) and therefore, indirectly, closely associated with the vertical gradient of ventilation.
Adult↗