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RATIONALE: The prone position is used to improve gas exchange in patients with acute respiratory distress syndrome. However, the regional mechanism by which the prone position improves gas exchange in acutely injured lungs is still incompletely defined. METHODS: We used positron emission tomography imaging of [(13)N]nitrogen to assess the regional distribution of pulmonary shunt, aeration, perfusion, and ventilation in seven surfactant-depleted sheep in supine and prone positions. RESULTS: In the supine position, the dorsal lung regions had a high shunt fraction, high perfusion, and poor aeration. The prone position was associated with an increase in lung gas content and with a more uniform distribution of aeration, as the increase in aeration in dorsal lung regions was not offset by loss of aeration in ventral regions. Consequently, the shunt fraction decreased in dorsal regions in the prone position without a concomitant impairment of gas exchange in ventral regions, thus leading to a significant increase in the fraction of pulmonary perfusion participating in gas exchange. In addition, the vertical distribution of specific alveolar ventilation became more uniform in the prone position. A biphasic relation between regional shunt fraction and gas fraction showed low shunt for values of gas fraction higher than a threshold, and a steep linear increase in shunt for lower values of gas fraction. CONCLUSION: In a surfactant-deficient model of lung injury, the prone position improved gas exchange by restoring aeration and decreasing shunt while preserving perfusion in dorsal lung regions, and by making the distribution of ventilation more uniform.

Plasma leakage has been regarded as the main technical problem during prolonged extracorporeal circulation (ECC) with microporous membrane oxygenators (MMOs). We report the case of a 15 year old male who underwent long term ECC for ARDS and in whom, by using new MMOs with reduced pore size, we were able to achieve prolonged artificial gas exchange efficiency with minimal plasma leakage. We conclude that reduced pore size MMOs might represent a valuable technical advance in extracorporeal oxygenation therapy

Rationale: During acute lung injury (ALI), mechanical ventilation can aggravate inflammation by promoting alveolar distension and cyclic recruitment-derecruitment. As an estimate of the intensity of inflammation,metabolic activity can bemeasured by positrone-mission tomography imaging of [18F]fluoro-2-deoxy-D-glucose. Objectives: To assess the relationship between gas volume changes induced by tidal ventilation and pulmonary metabolic activity in patients with ALI. Methods: In 13 mechanically ventilated patients with ALI and relatively high positive end-expiratory pressure, we performed a positron emission tomography scan of the chest and three computed tomography scans: at mean airway pressure, end-expiration, and end-inspiration. Metabolicactivitywasmeasuredfromthe[18F]fluoro-2-deoxy-D-glucose uptake rate. The computed tomography scans were used to classify lung regions as derecruited throughout the respiratory cycle, undergoing recruitment-derecruitment, and normally aerated. Measurements and Main Results: Metabolic activity of normally aerated lung was positively correlated both with plateau pressure, showing a pronounced increase above 26 to 27 cm H2O, and with regional VT normalized by end-expiratory lung gas volume. This relationship did not appear to be caused by a higher underlying parenchymal metabolic activity in patients with higher plateau pressure. Regions undergoing cyclic recruitment-derecruitment did not have higher metabolic activity than those collapsed throughout the respiratory cycle. Conclusions: In patients with ALI managed with relatively high end-expiratory pressure, metabolic activity of aerated regions was associated with both plateau pressure and regional VT normalized by end-expiratory lung gas volume, whereas no association was found between cyclic recruitment- derecruitment and increased metabolic activity. Copyright © 2011 American Thoracic Society.

OBJECTIVE:: Neutrophilic inflammation plays a key role in the pathogenesis of acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Positron emission tomography (PET) with [F]-fluoro-2-deoxy-d-glucose (FDG) can be used to image cellular metabolism that, during lung inflammatory processes, likely reflects neutrophils activity. The aim of this study was to assess the magnitude and regional distribution of inflammatory metabolic activity in the lungs of patients with ALI/ARDS by PET with FDG. DESIGN:: Prospective clinical investigation. PATIENTS:: Ten patients with ALI/ARDS; four spontaneously breathing and two mechanically ventilated subjects, without known lung disease, served as controls. INTERVENTIONS:: In each individual we performed an FDG PET/computed tomography of the thorax. MEASUREMENTS AND MAIN RESULTS:: FDG cellular influx rate constant (Ki) was computed for the imaged lung field and for regions of interest, grouping voxels with similar density. In all patients with ALI/ARDS, Ki was higher than in controls, also after accounting for the increased lung density. Ki values differed greatly among patients, but in all patients Ki of the normally aerated regions was much higher (2- to 24-fold) than in controls. Whereas in some patients the highest Ki values corresponded to regions with the lowest aeration, in others these regions had lower Ki than normally and mildly hypoaerated regions. CONCLUSION:: In patients with ALI/ARDS, undergoing mechanical ventilation since days, the metabolic activity of the lungs is markedly increased across the entire lung density spectrum. The intensity of this activation and its regional distribution, however, vary widely within and between patients. (C) 2009 Lippincott Williams & Wilkins, Inc.

Rationale: In a pulmonary process characterized by spatially heterogeneous loss of aeration, the impairment of gas exchange is expectedtodependonthe regional distribution of perfusion relative to that of aeration. Objectives: To investigate how regional aeration, shunt, and perfusion are interrelated at different levels of end-expiratory pressure and how their interplay relates to global shunt fraction in acute lung injury. Methods: Regional shunt and perfusion were assessed by imaging with positron emission tomography the pulmonary kinetics of [13N]nitrogen infused in saline solution in five sheep after lung lavage. The lung field was divided in six horizontal regions. Measurements and Main Results: Each animal showed an inverse relation betweenregional shunt (FS) and gas (FG) fractions: FS = -m·FG + FS 0. This relation was similar among animals (m = 1.25 ± 0.14, FS0 = 0.75 ± 0.15) and invariant with end-expiratory pressure, despite lack of correlation between global shunt and gas fractions and large interanimal variability in global shunt fraction. When this relation was used to estimate global shunt fraction as a perfusion-weighted average of the estimates of regional shunt fraction derived from regional gas fraction, 72% of the interanimal variability in global shunt fraction could be explained. Conclusions: Despite large interanimal variability in global shunt fraction, there was a consistent inverse relation between regional shunt and gas fractions, independent of end-expiratory pressure. Most of the interanimal variability in global shunt fraction could be explainedby thecombinedeffect of this relationandthe distribution of perfusion on regional shunt, rather than by differences in global aeration.

BACKGROUND: Alveolar overdistension and repetitive derecruitment-recruitment contribute to ventilator-induced lung injury (VILI). The authors investigated (1) whether inflammatory cell activation due to VILI was assessable by positron emission tomography and (2) whether cell activation due to dynamic overdistension alone was detectable when other manifestations of VILI were not yet evident. METHODS: The authors assessed cellular metabolic activity with [(18)F]fluorodeoxyglucose and regional gas exchange with [(13)N]nitrogen. In 12 sheep, the left ("test") lung was overdistended with end-inspiratory pressure of 50 cm H(2)O for 90 min, while end-expiratory derecruitment of this lung was either promoted with end-expiratory pressure of -10 cm H(2)O in 6 of these sheep (negative end-expiratory pressure [NEEP] group) or prevented with +10 cm H(2)O in the other 6 (positive end-expiratory pressure [PEEP] group) to isolate the effect of overdistension. The right ("control") lung was protected from VILI. RESULTS: Aeration decreased and shunt fraction increased in the test lung of the NEEP group. [(18)F]fluorodeoxyglucose uptake of this lung was higher than that of the control lung and of the test lung of the PEEP group, and correlated with neutrophil count. When normalized by tissue fraction to account for increased aeration of the test lung in the PEEP group, [(18)F]fluorodeoxyglucose uptake was elevated also in this group, despite the fact that gas exchange had not yet deteriorated after 90 min of overdistension alone. CONCLUSION: The authors could detect regional neutrophil activation in VILI even when end-expiratory derecruitment was prevented and impairment of gas exchange was not evident. Concomitant end-expiratory derecruitment converted this activation into profound inflammation with decreased aeration and regional shunting.

Asthma is a common disease affecting an increasing number of children throughout the world. In asthma, pulmonary airways narrow in response to contraction of surrounding smooth muscle. The precise nature of functional changes during an acute asthma attack is unclear. The tree structure of the pulmonary airways has been linked to complex behaviour in sudden airway narrowing and avalanche-like reopening. Here we present experimental evidence that bronchoconstriction leads to patchiness in lung ventilation, as well as a computational model that provides interpretation of the experimental data. Using positron emission tomography, we observe that bronchoconstricted asthmatics develop regions of poorly ventilated lung. Using the computational model we show that, even for uniform smooth muscle activation of a symmetric bronchial tree, the presence of minimal heterogeneity breaks the symmetry and leads to large clusters of poorly ventilated lung units. These clusters are generated by interaction of short- and long-range feedback mechanisms, which lead to catastrophic shifts similar to those linked to self-organized patchiness in nature. This work might have implications for the treatment of asthma, and might provide a model for studying diseases of other distributed organs.

At running speeds less than about 13 km h(-1) the freely chosen step frequency (f(free)) is lower than the frequency at which the mechanical power is minimized (f(min)). This dissociation between f(free) and f(min) was investigated by measuring mechanical power, metabolic energy expenditure and apparent natural frequency of the body's bouncing system (f(sist)) during running at three given speeds with different step frequencies. The f(free) requires a mechanical power greater than that at f(min) mainly due to a larger vertical oscillation of the body at each step. Energy expenditure is minimal and the mechanical efficiency is maximal at f(free). At a given speed, an increase in step frequency above f(free) results in an increase in energy expenditure despite a decrease in mechanical power. On the other hand, a decrease in step frequency below f(free) results in a larger increase in energy expenditure associated with an increase in mechanical power. When the step frequency is forced to values above or below f(free) f(sist) is forced to change similarly by adjusting the stiffness of the bouncing system. However the best match between f(sist) and step frequency takes place only in proximity of f(free) (2.6-2.8 Hz). It is concluded that during running at speeds less than 13 km h(-1) energy is saved by tuning step frequency to f(sist), even if this requires a mechanical power larger than necessary.