Effects on lung stress of position and different doses of perfluorocarbon in a model of ARDS.

We determined whether the combination of low dose partial liquid ventilation (PLV) with perfluorocarbons (PFC) and prone positioning improved lung function while inducing minimal stress. Eighteen pigs with acute lung injury were assigned to conventional mechanical ventilation (CMV) or PLV (5 or 10 ml/kg of PFC). Positive end-expiratory pressure (PEEP) trials in supine and prone positions were performed. Data were analyzed by a multivariate polynomial regression model. The interplay between PLV and position depended on the PEEP level. In supine PLV dampened the stress induced by increased PEEP during the trial. The PFC dose of 5 ml/kg was more effective than the dose 10 ml/kg. This effect was not observed in prone. Oxygenation was significantly higher in prone than in supine position mainly at lower levels of PEEP. In conclusion, MV settings should take both gas exchange and stress/strain into account. When protective CMV fails, rescue strategies combining prone positioning and PLV with optimal PEEP should improve gas exchange with minimal stress.

Dynamic nonlinearity of lung tissue: frequency dependence and harmonic distortion.

Harmonic distortion (HD) is a simple approach to analyze lung tissue nonlinear phenomena. This study aimed to characterize frequency-dependent behavior of HD at several amplitudes in lung tissue strips from healthy rats and its influence on the parameters of linear analysis. Lung strips (n = 17) were subjected to sinusoidal deformation at three different strain amplitudes (Δε) and fixed operational stress (12 hPa) among various frequencies, between 0.03 and 3 Hz. Input HD was <2% in all cases. The main findings in our study can be summarized as follows: 1) harmonic distortion of stress (HD) showed a positive frequency and amplitude dependence following a power law with frequency; 2) HD correlated significantly with the frequency response of dynamic elastance, seeming to converge to a limited range at an extrapolated point where HD=0; 3) the relationship between tissue damping (G) and HD(ω=1) (the harmonic distortion at ω=1 rad/s) was linear and accounted for a large part of the interindividual variability of G; 4) hysteresivity depended linearly on κ (the power law exponent of HD with ω); and 5) the error of the constant phase model could be corrected by taking into account the frequency dependence of harmonic distortion. We concluded that tissue elasticity and tissue damping are coupled at the level of the stress-bearing element and to the mechanisms underlying dynamic nonlinearity of lung tissue.

Volumetric capnography in acute respiratory distress syndrome / Capnografia volumétrica na síndrome do desconforto respiratório agudo

Volumetric capnography is especially sensitive to disturbances affecting the efficiency of ventilation for gas exchange. Because lung homogeneity is a very fragile property, it is endangered in the majority of diseases that affect the airways, lung parenchyma, or alveolar microcirculation. Acute lung injury and acute respiratory distress syndrome can be conveniently monitored with volumetric capnography. The combination of two advanced technologies—airway flow monitoring and mainstream capnography—allows breath-by-breath bedside computerized determination of the physiological dead space, alveolar heterogeneity, and CO2 elimination. The use of volumetric capnography at the bedside can provide clinicians with important physiological and prognostic data, as well as allowing the effects of therapeutic interventions to be evaluated in critical ill patients receiving mechanical ventilation.

A capnografia volumétrica é especialmente sensível aos problemas que afetam a eficiência da ventilação para a troca gasosa. Uma vez que a homogeneidade do pulmão é uma propriedade muito frágil, a medida da capnografia é um desafio na maioria das doenças que comprometem as vias aéreas, o parênquima pulmonar e a microcirculação alveolar. A lesão pulmonar aguda e síndrome do desconforto respiratório agudo são situações que devem ser monitoradas com a capnografia volumétrica. Essa tecnologia avançada é uma combinação da medida do fluxo aéreo e a capnografia convencional, fazendo com que seja possível computar, à beira do leito, parâmetros como espaço morto, heterogeneidade alveolar e eliminação do CO2. O uso da capnografia volumétrica à beira do leito pode fornecer aos clínicos importantes informações fisiológicas e sobre o prognóstico, assim como seguir o efeito de intervenções terapêuticas nos doentes críticos ventilados mecanicamente.

Dynamic nonlinearity of lung tissue: effects of strain amplitude and stress level.

Lung tissue presents substantial nonlinear phenomena not accounted for by linear models; however, nonlinear approaches are less available. Our aim was to characterize the behavior of total harmonic distortion, an index of nonlinearity, in lung tissue strips under sinusoidal deformation at a single frequency as a function of strain amplitude and operational stress. To that end, lung parenchymal strips from healthy rats (n = 6) were subjected to sinusoidal deformation (1 Hz) at different strain amplitudes (Δε = 4, 8, 12, 16, and 20%) and operating stresses (σ(op) = 6, 8, 10, 12, 14, and 16 hPa). Additional rats (n = 9) were intratracheally instilled with saline or bleomycin (2.5 U/kg, 3 times 1 wk apart), killed 28 days after the last instillation, and their lung tissue strips were studied at 5 and 10 hPa σ(op) and 5% Δε. In both cases, harmonic distortion (HD%) of input (strain) and output (stress) signals were determined. In healthy strips, HD% increased linearly with Δε, stress amplitude, and minimum stress by cycle variations, but showed no significant change with σ(op) levels. A prediction model could be determined as a function of operational stress and stress amplitude. Harmonic distortion was significantly increased in bleomycin-treated strips compared with controls and showed positive correlation with E behavior in both normal and diseased strips. We concluded that HD% can be useful as a single and simple parameter of lung tissue nonlinearity.

Different strains of mice present distinct lung tissue mechanics and extracellular matrix composition in a model of chronic allergic asthma.

The impact of genetic factors on asthma is well recognized but poorly understood. We tested the hypothesis that different mouse strains present different lung tissue strip mechanics in a model of chronic allergic asthma and that these mechanical differences may be potentially related to changes of extracellular matrix composition and/or contractile elements in lung parenchyma. Oscillatory mechanics were analysed before and after acetylcholine (ACh) in C57BL/10, BALB/c, and A/J mice, subjected or not to ovalbumin sensitization and challenge. In controls, tissue elastance (E) and resistance (R), collagen and elastic fibres' content, and alpha-actin were higher in A/J compared to BALB/c mice, which, in turn, were more elevated than in C57BL/10. A similar response pattern was observed in ovalbumin-challenged animals irrespective of mouse strain. E and R augmented more in ovalbumin-challenged A/J [E: 22%, R: 18%] than C57BL/10 mice [E: 9.4%, R: 11%] after ACh In conclusion, lung parenchyma remodelled differently yielding distinct in vitro mechanics according to mouse strain.

Prognostic value of different dead space indices in mechanically ventilated patients with acute lung injury and ARDS.

STUDY OBJECTIVE: The aim of this prospective observational study was to evaluate the utility of derived dead space indexes to predict survival in mechanically ventilated patients with acute lung injury (ALI) and ARDS. STUDY POPULATION: Thirty-six patients with ALI (Murray score, > or =1; Pao(2)/fraction of inspired oxygen [Fio(2)] ratio, < 300) in critical care departments at two separate hospitals entered the study. MEASUREMENTS: At ICU admission, 24 h, and 48 h, we measured the following: simplified acute physiologic score II; Pao(2)/Fio(2) ratio; respiratory system compliance; and capnographic indexes (Bohr dead space) and physiologic dead space (Enghoff dead space [Vdphys/Vt]), expired normalized CO(2) slope, carbon dioxide output, and the alveolar ejection volume (Vae)/tidal volume fraction (Vt) ratio. RESULTS: The best predictor was the Vae/Vt ratio at ICU admission (Vae/Vt-adm) and after 48 h (Vae/Vt-48 h) [p = 0.013], with a sensitivity of 82% and a specificity of 64%. The difference between Vae/Vt-48 h and Vae/Vt-adm show a sensitivity of 73% and a specificity of 93% with a likelihood ratio (LR) of 10.2 and an area under the receiver operating characteristic (ROC) curve of 0.83. The interaction between the Pao(2)/Fio(2) ratio and Vae/Vt-adm predict survival (p = 0.003) with an area under the ROC curve of 0.84, an LR of 2.3, a sensitivity of 100%, and a specificity of 57%. The Vdphys/Vt after 48 h predicted survival (p = 0.02) with an area under the ROC curve of 0.75, an LR of 8.8, a sensitivity of 63%, and a specificity of 93%. Indexes recorded 24 h after ICU admission were not useful in explaining outcome. CONCLUSIONS: Noninvasive measures of Vae/Vt at ICU admission and after 48 h of mechanical ventilation, associated with Pao(2)/Fio(2) ratio provided useful information on outcome in critically ill patients with ALI.

Volumetric capnography and chronic obstructive pulmonary disease staging.

Spirometry is difficult for some COPD patient to perform. Volumetric capnography could be a second choice test to evaluate the severity of functional disturbances. The aim of this work is to test this hypothesis. A total number of 98 subjects were classified either as normal ex-smokers (N=14) or COPD patients. The latter were staged following GOLD recommendations. Spirometry and volumetric capnography recordings were obtained from each patient. Spirometry parameters, Bohr Dead Space (V(D)Bohr), Airways Dead Space from the pre-interface expirate corrected curve (V(D)aw), Phase III slope (Sl(III)) and Volume of alveolar ejection (V(AE)) were measured. Index of Ventilatory Efficiency (IVE), and Index of Airways Heterogeneity (IAH) were calculated as: IVE = V(AE)/(V(T) - V(D)aw) and IAH = 1-[(V(T)-V(D)Bohr)/(V(T) - V(D)aw)]. In ANOCOVA analysis IAH showed the greatest association with stage (F >40), with no significant covariant dependence on V(T). A receiver operating characteristics curve analysis showed values of the area under the curve greater than 0.9 for IAH and IVE at all stage levels, with a sensitivity = specificity value greater than 80%. We conclude that IAH and IVE can be used when spirometry cannot be reliably performed, as an alternative test to evaluate the degree of functional involvement in COPD patients.

Mouse strain dependence of lung tissue mechanics: role of specific extracellular matrix composition.

This study analyses the differences between C57BL/10 and BALB/c mice in lung tissue micromechanical behaviour and whether specific histological characteristics are related to the mechanical profile. C57BL/10 and BALB/c subpleural lung strips were submitted to multisinusoidal deformation with frequencies ranging between 0.2 and 3.1 Hz. Tissue resistance (R), elastance (E), and hysteresivity (eta) at each frequency were determined before and 30s, 1, 2, and 3 min after acetylcholine (ACh) treatment. BALB/c mice showed higher E and R, at baseline, as well as greater amount of collagen and elastic fibres, and alpha-actin than C57BL/10 mice. However, E, R, and eta augmented with the same magnitude after ACh treatment in both strains. Baseline R was correlated with collagen fibre content and with the volume proportion of alpha-actin, while E was correlated with elastic and collagen fibres, and alpha-actin contents. In conclusion, BALB/c and C57BL/10 mice present distinct tissue mechanical properties that are accompanied by specific extracellular matrix composition and contractile structures.

Massive brain injury enhances lung damage in an isolated lung model of ventilator-induced lung injury.

OBJECTIVE: To assess the influence of massive brain injury on pulmonary susceptibility to injury attending subsequent mechanical or ischemia/reperfusion stress. DESIGN: Prospective experimental study. SETTING: Animal research laboratory. SUBJECTS: Twenty-four anesthetized New Zealand White rabbits randomized to control (n = 12) or induced brain injury (n = 12) group. INTERVENTIONS: After randomization, brain injury was induced by inflation of an intracranial balloon-tipped catheter, and animals were ventilated with a tidal volume of 10 mL/kg and zero end-expiratory pressure for 120 mins. Following heart-lung block extraction, isolated and perfused lungs were subjected to injurious ventilation with peak airway pressure 30 cm H2O and positive end-expiratory pressure 5 cm H2O for 30 mins. MEASUREMENTS AND MAIN RESULTS: No difference was observed between groups in gas exchange, lung mechanics, or hemodynamics during the 2-hr in vivo period following induction of brain injury. However, after 30 mins of ex vivo injurious mechanical ventilation, lungs from the brain injury group showed greater change in ultrafiltration coefficient, weight gain, and alveolar hemorrhage (all p < .05). CONCLUSIONS: Massive brain injury might increase lung vulnerability to subsequent injurious mechanical or ischemia-reperfusion insults, thereby increasing the risk of clinical posttransplant graft failure.

Persistence of lung function abnormalities despite sustained success of percutaneous mitral valvotomy: the need for an early indication.

AIMS: We assessed early and long-term pulmonary function changes after percutaneous balloon mitral valvotomy (PBMV). METHODS AND RESULTS: Mitral area, lung function, and exercise capacity were evaluated before, immediately after, and 3 months, 6 months, and 12 months after successful PBMV in 24 patients. PBMV resulted in a significant and sustained increase in mitral area, from 1.0 +/- 0.1 to 1.9 +/- 0.1 cm2 (p = 0.001) [mean +/- SD], with a progressive increase in exercise tolerance at 6-month follow-up (from 22.6 +/- 1.4 to 28.2 +/- 1.2 mL/kg, p = 0.0001). An immediate drop in the diffusing capacity of the lung for carbon monoxide (DLCO) was observed (from 26.7 +/- 1.5 to 22.3 +/- 1.1 mL/min/mm Hg, p = 0.0002) after PBMV, followed by a gradual regression to baseline values at 3 months; at 1 year, the DLCO remained elevated (27.3 +/- 6.3 mL/min/mm Hg). The flow in the small airways was reduced at baseline, and there was no significant change during follow-up. CONCLUSIONS: PBMV produces an initial decrease in DLCO, suggesting a reduction of pulmonary congestion. During follow-up, the regression to the initial lung diffusion values despite a sustained hemodynamic improvement suggests that some irreversible interstitial changes were present. In patients with mitral stenosis, an impairment of lung function parameters suggests that PBMV must be performed early, even if patients have few symptoms.

What increases type III procollagen mRNA levels in lung tissue: stress induced by changes in force or amplitude?

We hypothesized that stress determined by force could induce higher type III procollagen (PCIII) mRNA expression than the stress determined by amplitude. To that end, rat lung tissue strips were oscillated for 1h under different amplitudes [1, 5 and 10% of resting length (L(B)), at 0.5 x 10(-2) N] and forces (0.25 x 10(-2), 0.5 x 10(-2) and 10(-2)N, at 5% L(B)). Resistance (R), elastance (E) and hysteresivity (eta) were analysed during sinusoidal oscillations at 1Hz. After 1h of oscillation, PCIII mRNA expression was determined by Northern-blot and semiquantitative RT-PCR. Control value of PCIII mRNA was obtained from unstressed strips. E and R increased with augmenting force and decreased with increasing amplitude, while eta remained unaltered. PCIII mRNA expression increased significantly after 1h of oscillation at 10(-2)N and 5% L(B) and remained unchanged for 6h. In conclusion, the stress induced by force but not by amplitude led to the increment in PCIII mRNA expression.

Utility of oxygen saturation and heart rate spectral analysis obtained from pulse oximetric recordings in the diagnosis of sleep apnea syndrome.

OBJECTIVES: We prospectively evaluate the spectral characteristics of nocturnal arterial oxygen saturation (SaO(2)) and heart rate variability obtained from pulse oximetric recording as a diagnostic test for obstructive sleep apnea (OSA). SUBJECTS AND MEASUREMENTS: Three hundred referred outpatients with symptoms compatible with the diagnosis of OSA were studied using nocturnal pulse oximetric recording performed simultaneously with polysomnography. Power spectral analysis of SaO(2) and heart rate data were analyzed using fast Fourier transformation of a Hamming-windowed signal. DESIGN AND RESULTS: Recording test results were classified as abnormal (suspicion of OSA) if the periodogram showed a peak in the period 30 to 70 s in either of the signals. A normal test result was defined as the absence of this peak in the periodogram in both signals. Two independent observers performed a single-blind evaluation. The total area of the periodogram (STOT), the ratio of the area enclosed in the periodogram within the period 30 to 70 s (S(30-70)), the ratio of the area enclosed in the periodogram within the period 30 to 70 s with respect to the total area of the periodogram (S), and the peak amplitude of the periodogram in the period 30 to 70 s (PA) were measured in both signals. The presence of a peak in the periodogram in either of the signals has a sensitivity of 94%, a specificity of 82%, a positive predictive value of 87%, and a negative predictive value of 92% with respect to the OSA diagnosis. The patients in the OSA group had higher values for STOT, S(30-70), S, and PA than the group without OSA. CONCLUSIONS: SaO(2) and heart rate spectral analysis obtained by nocturnal pulse oximetry as well as the identification of a peak within 30 to 70 s in either signal could be useful as a diagnostic technique for patient with OSA.

On the preparation of lung strip for tissue mechanics measurement.

It is widely believed that it is fundamental to degas and/or rinse the lung prior to the measurement of the tissue mechanics, so that the undesirable effects of surfactant and localized gas trapping are eliminated. However, one could hypothesize that these mechanisms are bound to disappear in the in vitro preparation since the small tissue sample remains suspended oscillating in an organ bath. To investigate the real necessity to follow these procedures, dynamic mechanical properties were studied in strips of lungs previously rinsed with saline, degassed by ventilation with 100% O(2), or without any of these prior procedures. Resistance, elastance, hysteresivity, and the amounts of airway, blood vessel, and alveolar wall were computed. There was no difference in either tissue mechanics or morphology among the groups. In conclusion, the time-consuming degassing and rinsing steps are not necessary to adequately prepare lung tissue for in vitro mechanical analysis, and eliminating these steps potentially helps preserving the intact microstructure of the tissue.

Evaluation of a noninvasive method for cardiac output measurement in critical care patients.

OBJECTIVE: Thermodilution (TD) is the gold standard to monitor cardiac output (CO) in critical care. However, there is concern about the safety of right-ventricular catheterization. The CO(2) rebreathing technique allows noninvasive CO determination by means of the indirect Fick principle. Our objectives were: (a) to assess the accuracy of a new system of CO measurement using the CO(2) partial rebreathing method (PRCO); (b) to evaluate whether the PRCO itself may induce changes in CO. DESIGN AND SETTING: Prospective study in the intensive care department in a university-affiliated hospital. PATIENTS: Twenty-two mechanically ventilated critically ill patients. INTERVENTIONS: CO measured simultaneously by PRCO and TDCO. MEASUREMENTS AND RESULTS: PRCO and TDCO values were compared by concordance analysis. Stability of cardiac output during PRCO was evaluated by comparing the TDCO measurements before, during, and after the partial rebreathing period using analysis of variance. From a total of 79 valid sets of measurements, bias and precision was calculated at -0.18+/-1.39 l/min. The concordance analysis of lower and intermediate CO values (<7 l/min) yielded a bias and precision calculation of -0.07+/-0.91 l/min. No changes in hemodynamics were observed during the partial rebreathing period. CONCLUSIONS: The noninvasive partial CO(2) rebreathing technique may be an alternative method for CO determination in mechanically ventilated critically ill patients. The rebreathing maneuver alone does not induce changes in CO.