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The contribution of aeration heterogeneity to lung injury during early mechanical ventilation of uninjured lungs is unknown. To test the hypotheses that a strategy consistent with clinical practice does not protect from worsening in lung strains during the first 24 hours of ventilation of initially normal lungs exposed to mild systemic endotoxemia in supine versus prone position, and that local neutrophilic inflammation is associated with local strain and blood volume at global strains below a proposed injurious threshold. Voxel-level aeration and tidal strain were assessed by computed tomography in sheep ventilated with low Vt and positive end-expiratory pressure while receiving intravenous endotoxin. Regional inflammation and blood volume were estimated from 2-deoxy-2-[(18)F]fluoro-d-glucose ( F-FDG) positron emission tomography. Spatial heterogeneity of aeration and strain increased only in supine lungs (P < 0.001), with higher strains and atelectasis than prone at 24 hours. Absolute strains were lower than those considered globally injurious. Strains redistributed to higher aeration areas as lung injury progressed in supine lungs. At 24 hours, tissue-normalized F-FDG uptake increased more in atelectatic and moderately high-aeration regions (>70%) than in normally aerated regions (P < 0.01), with differential mechanistically relevant regional gene expression. F-FDG phosphorylation rate was associated with strain and blood volume. Imaging findings were confirmed in ventilated patients with sepsis. Mechanical ventilation consistent with clinical practice did not generate excessive regional strain in heterogeneously aerated supine lungs. However, it allowed worsening of spatial strain distribution in these lungs, associated with increased inflammation. Our results support the implementation of early aeration homogenization in normal lungs.

Regional pulmonary perfusion (Q) has been investigated using blood volume (F b ) imaging as an easier-to-measure surrogate. However, it is unclear if changing pulmonary conditions could affect their relationship. We hypothesized that vascular changes in early acute respiratory distress syndrome (ARDS) affect Q and F b differently. Five sheep were anesthetized and received lung protective mechanical ventilation for 20 h while endotoxin was continuously infused. Using dynamic 18 F-FDG and 13 NN Positron Emission Tomography (PET), regional F b and Q were analysed in 30 regions of interest (ROIs) and normalized by tissue content (F bn and Q n , respectively). After 20 h, the lung injury showed characteristics of early ARDS, including gas exchange and lung mechanics. PET images of F bn and Q n showed substantial differences between baseline and lung injury. Lung injury caused a significant change in the F bn -Q n relationship compared to baseline (p < 0.001). The best models at baseline and lung injury were F bn  = 0.32 + 0.690Q n and F bn  = 1.684Q n –0.538Q n 2 , respectively. Endotoxine-associated early ARDS changed the relationship between F b and Q, shifting from linear to curvilinear. Effects of endotoxin exposure on the vasoactive blood flow regulation were most likely the key factor for this change limiting the quantitative accuracy of F b imaging as a surrogate for regional Q.

To compare the effects of four levels of end-expiratory pressure [zero (ZEEP) and three levels of positive end-expiratory pressure (PEEP)] on the cardiovascular system and gas exchange of cats anesthetized with isoflurane and mechanically ventilated for 3 h with a tidal volume of 10 ml/kg. Prospective, randomized, controlled trial. Six healthy male neutered purpose-bred cats. Anesthesia was induced with isoflurane and maintained at 1.3 minimum alveolar concentration. PEEP of maximal respiratory compliance (PEEP ) was identified in a decremental PEEP titration, and cats were randomly ventilated for 3 h with one of the following end-expiratory pressures: ZEEP, PEEP minus 2 cmH O (PEEP ), PEEP , and PEEP plus 2 cmH O (PEEP ). Cardiovascular and gas exchange variables were recorded at 5, 30, 60, 120, and 180 min (T5 to T180, respectively) of ventilation and compared between and within ventilation treatments with mixed-model ANOVA followed by Dunnet's and Tukey's tests (normal distribution) or Friedman test followed by the Dunn's test (non-normal distribution). Significance to reject the null hypothesis was considered < 0.05. Mean arterial pressure (MAP-mmHg) was lower in PEEP [63 (49-69); median (range)] when compared to ZEEP [71 (67-113)] at T5 and stroke index (ml/beat/kg) was lower in PEEP (0.70 ± 0.20; mean ± SD) than in ZEEP (0.90 ± 0.20) at T60. Cardiac index, oxygen delivery index (DO I), systemic vascular resistance index, and shunt fraction were not significantly different between treatments. The ratio between arterial partial pressure and inspired concentration of oxygen (PaO /FIO ) was lower in ZEEP than in the PEEP treatments at various time points. At T180, DO I was higher when compared to T5 in PEEP . Dopamine was required to maintain MAP higher than 60 mmHg in one cat during PEEP and in three cats during PEEP . In cats anesthetized with isoflurane and mechanically ventilated for 3 h, all levels of PEEP mildly improved gas exchange with no significant difference in DO I when compared to ZEEP. The PEEP levels higher than PEEP caused more cardiovascular depression, and dopamine was an effective treatment. A temporal increase in DO I was observed in the cats ventilated with PEEP . The effects of these levels of PEEP on respiratory mechanics, ventilation-induced lung injury, as well as in obese and critically ill cats deserve future investigation for a better understanding of the clinical use of PEEP in this species.

Emotional states can guide the actions and decisions we make in our everyday life through their influence on cognitive processes such as working memory (WM). We investigated the long-lasting interference that an unpleasant emotional state had on goal-relevant WM representations from an electrophysiological perspective. Participants performed a change detection task that was preceded by the presentation of unpleasant or neutral task-irrelevant pictures in a blocked fashion. We focused on the contralateral delay activity (CDA), an event-related potential that is sensitive to the number of task-relevant items stored in WM. We found that the asymptotic limit for the CDA amplitude was lower during the unpleasant emotional state than during the neutral one; that is, an emotional state was capable of reducing how many task-relevant items the participants could hold in WM. Furthermore, both the individuals who experienced more intrusive thoughts and those who were dispositionally anxious were more susceptible to the influence of the emotional state. We provide evidence that an unpleasant emotional state diminished visual WM for task-relevant items, particularly in susceptible individuals. These results open new avenues to uncover the emotional-cognitive processing that underlies maladaptive WM representations and the role of such processing in the development of mental illness.