Search

Background: Despite being essential in patients with acute respiratory distress syndrome (ARDS), mechanical ventilation (MV) may cause lung injury and hemodynamic instability. Mechanical power (MP) may describe the net injurious effects of MV, but whether it reflects the hemodynamic effects of MV is currently unclear. We hypothesized that MP is also associated with cardiac output (CO) and pulmonary blood flow (PBF)., Methods: 24 anesthetized pigs with experimental acute lung injury were ventilated for 18 h according to one of three strategies: 1) Open lung approach (OLA), 2) ARDS Network high-PEEP/F I O 2 strategy (HighPEEP), or 3) low-PEEP/F I O 2 strategy (LowPEEP). Total MP was assessed as the sum of energy dissipated to overcome airway resistance and energy temporarily stored in the elastic lung tissue per minute. The distribution of pulmonary perfusion was determined by positron emission tomography. Regional PBF and MP, assessed in three iso-gravitational regions of interest (ROI) with equal lung mass (ventral, middle, and dorsal ROI), were compared between groups., Results: MP was higher in the LowPEEP than in the OLA group, while CO did not differ between groups. After 18 h, regional PBF did not differ between groups. During LowPEEP, regional MP was higher in the ventral ROI compared to OLA and HighPEEP groups (2.5 ± 0.3 vs. 1.4 ± 0.4 and 1.6 ± 0.3 J/min, respectively, P < 0.001 each), and higher in the middle ROI compared to the OLA group (2.5 ± 0.4 vs. 1.6 ± 0.5 J/min, P = 0.04). MP in the dorsal ROI did not differ between groups (1.4 ± 0.9 vs. 1.4 ± 0.5 vs. 1.3 ± 0.8 J/min, P = 0.916). Total MP was independently associated with CO [0.34 (0.09, 0.59), P = 0.020]. Regional MP was positively associated with PBF irrespective of the regions [0.52 (0.14, 0.76), P = 0.01; 0.49 (0.10, 0.74), P = 0.016; 0.64 (0.32, 0.83), P = 0.001 for ventral, middle, and dorsal ROI, respectively]. Subgroup analysis revealed a significant association of MP and CO only in the OLA group as well as a significant association between MP with regional PBF only in the HighPEEP group., Conclusion: In this model of acute lung injury in pigs ventilated with either open lung approach, high, or low PEEP tables recommended by the ARDS network, MP correlated positively with CO and regional PBF, whereby these clinically relevant lung-protective ventilation strategies influenced the associations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Wittenstein, Braune, Theilen, Maiello, Benzi, Bluth, Kiss, Ran, Koch, Rocco, J. Schultz, Kotzerke, Gama De Abreu, Huhle and Scharffenberg.)

Background: Mechanical ventilation (MV) is a life supporting therapy but may also cause lung damage. This phenomenon is known as ventilator-induced lung injury (VILI). A potential pathomechanisms of ventilator-induced lung injury may be the stretch-induced production and release of cytokines and pro-inflammatory molecules from the alveolar epithelium. Yes-associated protein (YAP) might be regulated by mechanical forces and involved in the inflammation cascade. However, its role in stretch-induced damage of alveolar cells remains poorly understood. In this study, we explored the role of YAP in the response of alveolar epithelial type II cells (AEC II) to elevated cyclic stretch in vitro . We hypothesize that Yes-associated protein activates its downstream targets and regulates the interleukin-6 (IL-6) expression in response to 30% cyclic stretch in AEC II. Methods: The rat lung L2 cell line was exposed to 30% cyclic equibiaxial stretch for 1 or 4 h. Non-stretched conditions served as controls. The cytoskeleton remodeling and cell junction integrity were evaluated by F-actin and Pan-cadherin immunofluorescence, respectively. The gene expression and protein levels of IL-6, Yes-associated protein, Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1), and connective tissue growth factor (CTGF/CCN2) were studied by real-time polymerase chain reaction (RT-qPCR) and Western blot, respectively. Verteporfin (VP) was used to inhibit Yes-associated protein activation. The effects of 30% cyclic stretch were assessed by two-way ANOVA. Statistical significance as accepted at p < 0.05. Results: Cyclic stretch of 30% induced YAP nuclear accumulation, activated the transcription of Yes-associated protein downstream targets Cyr61/CCN1 and CTGF/CCN2 and elevated IL-6 expression in AEC II after 1 hour, compared to static control. VP (2 µM) inhibited Yes-associated protein activation in response to 30% cyclic stretch and reduced IL-6 protein levels. Conclusion: In rat lung L2 AEC II, 30% cyclic stretch activated YAP, and its downstream targets Cyr61/CCN1 and CTGF/CCN2 and proinflammatory IL-6 expression. Target activation was blocked by a Yes-associated protein inhibitor. This novel YAP-dependent pathway could be involved in stretch-induced damage of alveolar cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ran, Müller, Brunssen, Huhle, Scharffenberg, Schnabel, Koch, Gama de Abreu, Morawietz, Ferreira and Wittenstein.)

Background . Global and regional transpulmonary pressure (P L ) during one-lung ventilation (OLV) is poorly characterized. We hypothesized that global and regional P L and driving P L (ΔP L ) increase during protective low tidal volume OLV compared to two-lung ventilation (TLV), and vary with body position. Methods . In sixteen anesthetized juvenile pigs, intra-pleural pressure sensors were placed in ventral, dorsal, and caudal zones of the left hemithorax by video-assisted thoracoscopy. A right thoracotomy was performed and lipopolysaccharide administered intravenously to mimic the inflammatory response due to thoracic surgery. Animals were ventilated in a volume-controlled mode with a tidal volume (V T ) of 6 mL kg -1 during TLV and of 5 mL kg -1 during OLV and a positive end-expiratory pressure (PEEP) of 5 cmH 2 O. Global and local transpulmonary pressures were calculated. Lung instability was defined as end-expiratory P L <2.9 cmH 2 O according to previous investigations. Variables were acquired during TLV (TLVsupine), left lung ventilation in supine (OLVsupine), semilateral (OLVsemilateral), lateral (OLVlateral) and prone (OLVprone) positions randomized according to Latin-square sequence. Effects of position were tested using repeated measures ANOVA. Results . End-expiratory P L and ΔP L were higher during OLVsupine than TLVsupine. During OLV, regional end-inspiratory P L and ΔP L did not differ significantly among body positions. Yet, end-expiratory P L was lower in semilateral (ventral: 4.8 ± 2.9 cmH 2 O; caudal: 3.1 ± 2.6 cmH 2 O) and lateral (ventral: 1.9 ± 3.3 cmH 2 O; caudal: 2.7 ± 1.7 cmH 2 O) compared to supine (ventral: 4.8 ± 2.9 cmH 2 O; caudal: 3.1 ± 2.6 cmH 2 O) and prone position (ventral: 1.7 ± 2.5 cmH 2 O; caudal: 3.3 ± 1.6 cmH 2 O), mainly in ventral ( p ≤ 0.001) and caudal ( p = 0.007) regions. Lung instability was detected more often in semilateral (26 out of 48 measurements; p = 0.012) and lateral (29 out of 48 measurements, p < 0.001) as compared to supine position (15 out of 48 measurements), and more often in lateral as compared to prone position (19 out of 48 measurements, p = 0.027). Conclusion . Compared to TLV, OLV increased lung stress. Body position did not affect stress of the ventilated lung during OLV, but lung stability was lowest in semilateral and lateral decubitus position., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wittenstein, Scharffenberg, Yang, Bluth, Kiss, Schultz, Rocco, Pelosi, Gama de Abreu and Huhle.)

Background: Mechanical ventilation (MV) may initiate or worsen lung injury, so-called ventilator-induced lung injury (VILI). Although different mechanisms of VILI have been identified, research mainly focused on single ventilator parameters. The mechanical power (MP) summarizes the potentially damaging effects of different parameters in one single variable and has been shown to be associated with lung damage. However, to date, the association of MP with pulmonary neutrophilic inflammation, as assessed by positron-emission tomography (PET), has not been prospectively investigated in a model of clinically relevant ventilation settings yet. We hypothesized that the degree of neutrophilic inflammation correlates with MP. Methods: Eight female juvenile pigs were anesthetized and mechanically ventilated. Lung injury was induced by repetitive lung lavages followed by initial PET and computed tomography (CT) scans. Animals were then ventilated according to the acute respiratory distress syndrome (ARDS) network recommendations, using the lowest combinations of positive end-expiratory pressure and inspiratory oxygen fraction that allowed adequate oxygenation. Ventilator settings were checked and adjusted hourly. Physiological measurements were conducted every 6 h. Lung imaging was repeated 24 h after first PET/CT before animals were killed. Pulmonary neutrophilic inflammation was assessed by normalized uptake rate of 2-deoxy-2-[ 18 F]fluoro-D-glucose (K iS ), and its difference between the two PET/CT was calculated (ΔK iS ). Lung aeration was assessed by lung CT scan. MP was calculated from the recorded pressure-volume curve. Statistics included the Wilcoxon tests and non-parametric Spearman correlation. Results: Normalized 18 F-FDG uptake rate increased significantly from first to second PET/CT ( p = 0.012). ΔK iS significantly correlated with median MP (ρ = 0.738, p = 0.037) and its elastic and resistive components, but neither with median peak, plateau, end-expiratory, driving, and transpulmonary driving pressures, nor respiratory rate (RR), elastance, or resistance. Lung mass and volume significantly decreased, whereas relative mass of hyper-aerated lung compartment increased after 24 h ( p = 0.012, p = 0.036, and p = 0.025, respectively). Resistance and PaCO 2 were significantly higher ( p = 0.012 and p = 0.017, respectively), whereas RR, end-expiratory pressure, and MP were lower at 18 h compared to start of intervention. Conclusions: In this model of experimental acute lung injury in pigs, pulmonary neutrophilic inflammation evaluated by PET/CT increased after 24 h of MV, and correlated with MP., Competing Interests: MG received consultation fees from Dräger, Ambu, GE Healthcare, and ZOLL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Scharffenberg, Wittenstein, Ran, Zhang, Braune, Theilen, Maiello, Benzi, Bluth, Kiss, Pelosi, Rocco, Schultz, Kotzerke, Gama de Abreu and Huhle.)

Background: The incidence of hypoxemia during one-lung ventilation (OLV) is as high as 10%. It is also partially determined by the distribution of perfusion. During thoracic surgery, different body positions are used, such as the supine, semilateral, lateral, and prone positions, with such positions potentially influencing the distribution of perfusion. Furthermore, hypovolemia can impair hypoxic vasoconstriction. However, the effects of body position and hypovolemia on the distribution of perfusion remain poorly defined. We hypothesized that, during OLV, the relative perfusion of the ventilated lung is higher in the lateral decubitus position and that hypovolemia impairs the redistribution of pulmonary blood flow. Methods: Sixteen juvenile pigs were anesthetized, mechanically ventilated, submitted to a right-sided thoracotomy, and randomly assigned to one of two groups: (1) intravascular normovolemia or (2) intravascular hypovolemia, as achieved by drawing ~25% of the estimated blood volume ( n = 8/group). Furthermore, to mimic thoracic surgery inflammatory conditions, Escherichia coli lipopolysaccharide was continuously infused at 0.5 μg kg -1 h -1 . Under left-sided OLV conditions, the animals were further randomized to one of the four sequences of supine, left semilateral, left lateral, and prone positioning. Measurements of pulmonary perfusion distribution with fluorescence-marked microspheres, ventilation distribution by electrical impedance tomography, and gas exchange were then performed during two-lung ventilation in a supine position and after 30 min in each position and intravascular volume status during OLV. Results: During one-lung ventilation, the relative perfusion of the ventilated lung was higher in the lateral than the supine position. The relative perfusion of the non-ventilated lung was lower in the lateral than the supine and prone positions and in semilateral compared with the prone position. During OLV, the highest arterial partial pressure of oxygen/inspiratory fraction of oxygen (PaO 2 / F I O 2 ) was achieved in the lateral position as compared with all the other positions. The distribution of perfusion, ventilation, and oxygenation did not differ significantly between normovolemia and hypovolemia. Conclusions: During one-lung ventilation in endotoxemic pigs, the relative perfusion of the ventilated lung and oxygenation were higher in the lateral than in the supine position and not impaired by hypovolemia., Competing Interests: MG received consultation fees from Dräger, Ambu, GE Healthcare, and ZOLL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wittenstein, Scharffenberg, Ran, Zhang, Keller, Tauer, Theilen, Chai, Ferreira, Müller, Bluth, Kiss, Schultz, Rocco, Pelosi, Gama de Abreu and Huhle.)