Dataset Information

Brain injury after 50 h of lung-protective mechanical ventilation in a preclinical model.

ABSTRACT: Mechanical ventilation is the cornerstone of the Intensive Care Unit. However, it has been associated with many negative consequences. Recently, ventilator-induced brain injury has been reported in rodents under injurious ventilation settings. Our group wanted to explore the extent of brain injury after 50 h of mechanical ventilation, sedation and physical immobility, quantifying hippocampal apoptosis and inflammation, in a normal-lung porcine study. After 50 h of lung-protective mechanical ventilation, sedation and immobility, greater levels of hippocampal apoptosis and neuroinflammation were clearly observed in the mechanically ventilated group, in comparison to a never-ventilated group. Markers in the serum for astrocyte damage and neuronal damage were also higher in the mechanically ventilated group. Therefore, our study demonstrated that considerable hippocampal insult can be observed after 50 h of lung-protective mechanical ventilation, sedation and physical immobility.

SUBMITTER: Bassi TG

PROVIDER: S-EPMC7930247 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Brain injury after 50 h of lung-protective mechanical ventilation in a preclinical model.

Bassi Thiago G TG Rohrs Elizabeth C EC Fernandez Karl C KC Ornowska Marlena M Nicholas Michelle M Gani Matt M Evans Doug D Reynolds Steven C SC

Scientific reports 20210303 1

Mechanical ventilation is the cornerstone of the Intensive Care Unit. However, it has been associated with many negative consequences. Recently, ventilator-induced brain injury has been reported in rodents under injurious ventilation settings. Our group wanted to explore the extent of brain injury after 50 h of mechanical ventilation, sedation and physical immobility, quantifying hippocampal apoptosis and inflammation, in a normal-lung porcine study. After 50 h of lung-protective mechanical vent ...[more]

PMID: 33658581

Similar Datasets

Project description:Introduction: The ideal ventilation strategy for patients with massive brain damage requires better elucidation. We hypothesized that in the presence of massive brain injury, a ventilation strategy using low (6 mL/kg) tidal volume (VT) ventilation with open lung positive end-expiratory pressure set according to the minimal static elastance of the respiratory system (LVT/OLPEEP), attenuate the impact of massive brain damage on gas-exchange, respiratory mechanics, lung histology and whole genome alterations compared with high (12 mL/kg) VT and low PEEP ventilation (HVT/LPEEP). Methods: Twenty-eight adult male Wistar rats were randomly assigned to one of four groups: 1) no brain damage (NBD) with LVT/OLPEEP; 2) NBD with HVT/LPEEP; 3) brain damage (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. All animals were mechanically ventilated for six hours. Brain damage was induced by an inflated balloon catheter into the epidural space. Hemodynamics was recorded and blood gas analysis was performed hourly. At the end of the experiment, respiratory system mechanics and lung histology were analysed. Whole genome analysis was performed using Affimetrix gene chips and confirmatory real-time PCR. Results: In NBD, both LVT/OLPEEP and HVT/LPEEP did not affect arterial blood gases, as well as whole genome expression changes and real-time PCR. In BD, LVT/OLPEEP, compared to HVT/LPEEP, reduced lung damage according to histology, genome analysis and real-time PCR with decreased interleukin (IL-6), cytokine-induced neutrophil chemoattractant (CINC)-1 and angiopoietin-4 expressions. LVT/OLPEEP compared to HVT/LPEEP improved overall survival. Conclusions: In BD, LVT/OLPEEP minimizes lung morpho-functional changes and inflammation compared to HVT/LPEEP. LVT/OLPEEP might represent a suitable ventilatory strategy in massive brain damage. 24 Wistar rats - lung samples, 4 groups, 1. non-braindamaged/braindead high tidal volume ventilation, 2. non-braindamaged/braindead best PEEP ventilation, 3. Braindamaged/braindead high tidal volume ventilation, 4. Braindamaged/braindead best PEEP ventilation

Project description:BACKGROUND:The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM) injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT) in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response. METHODS:Pregnant ewes (n?=?18) received intra-amniotic lipopolysaccharide (LPS) 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n?=?6), or were ventilated using an injurious high VT strategy (LPSINJ; n?=?5) or a protective ventilation strategy (LPSPROT; n?=?7) for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury. RESULTS:LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02) and cell death (p<0.05) in the WM, which were equivalent in magnitude between groups. CONCLUSIONS:Ventilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor to WM injury in infants exposed to chorioamnionitis.

Project description:Acute respiratory distress syndrome (ARDS) is associated with a heterogeneous pattern of injury throughout the lung parenchyma that alters regional alveolar opening and collapse time constants. Such heterogeneity leads to atelectasis and repetitive alveolar collapse and expansion (RACE). The net effect is a progressive loss of lung volume with secondary ventilator-induced lung injury (VILI). Previous concepts of ARDS pathophysiology envisioned a two-compartment system: a small amount of normally aerated lung tissue in the non-dependent regions (termed "baby lung"); and a collapsed and edematous tissue in dependent regions. Based on such compartmentalization, two protective ventilation strategies have been developed: (1) a "protective lung approach" (PLA), designed to reduce overdistension in the remaining aerated compartment using a low tidal volume; and (2) an "open lung approach" (OLA), which first attempts to open the collapsed lung tissue over a short time frame (seconds or minutes) with an initial recruitment maneuver, and then stabilize newly recruited tissue using titrated positive end-expiratory pressure (PEEP). A more recent understanding of ARDS pathophysiology identifies regional alveolar instability and collapse (i.e., hidden micro-atelectasis) in both lung compartments as a primary VILI mechanism. Based on this understanding, we propose an alternative strategy to ventilating the injured lung, which we term a "stabilize lung approach" (SLA). The SLA is designed to immediately stabilize the lung and reduce RACE while gradually reopening collapsed tissue over hours or days. At the core of SLA is time-controlled adaptive ventilation (TCAV), a method to adjust the parameters of the airway pressure release ventilation (APRV) modality. Since the acutely injured lung at any given airway pressure requires more time for alveolar recruitment and less time for alveolar collapse, SLA adjusts inspiratory and expiratory durations and inflation pressure levels. The TCAV method SLA reverses the open first and stabilize second OLA method by: (i) immediately stabilizing lung tissue using a very brief exhalation time (≤0.5 s), so that alveoli simply do not have sufficient time to collapse. The exhalation duration is personalized and adaptive to individual respiratory mechanical properties (i.e., elastic recoil); and (ii) gradually recruiting collapsed lung tissue using an inflate and brake ratchet combined with an extended inspiratory duration (4-6 s) method. Translational animal studies, clinical statistical analysis, and case reports support the use of TCAV as an efficacious lung protective strategy.

Project description:BackgroundProtective ventilation with lower tidal volumes reduces systemic and organ-specific inflammation. In sepsis-induced encephalopathy or acute brain injury the use of protective ventilation has not been widely investigated (experimentally or clinically). We hypothesized that protective ventilation would attenuate cerebral inflammation in a porcine endotoxemic sepsis model. The aim of the study was to study the effect of tidal volume on cerebral inflammatory response, cerebral metabolism and brain injury. Nine animals received protective mechanical ventilation with a tidal volume of 6 mL × kg-1 and nine animals were ventilated with a tidal volume of 10 mL × kg-1. During a 6-h experiment, the pigs received an endotoxin intravenous infusion of 0.25 µg × kg-1 × h-1. Systemic, superior sagittal sinus and jugular vein blood samples were analysed for inflammatory cytokines and S100B. Intracranial pressure, brain tissue oxygenation and brain microdialysis were sampled every hour.ResultsNo differences in systemic or sagittal sinus levels of TNF-α or IL-6 were seen between the groups. The low tidal volume group had increased cerebral blood flow (p < 0.001) and cerebral oxygen delivery (p < 0.001), lower cerebral vascular resistance (p < 0.05), higher cerebral metabolic rate (p < 0.05) along with higher cerebral glucose consumption (p < 0.05) and lactate production (p < 0.05). Moreover, low tidal volume ventilation increased the levels of glutamate (p < 0.01), glycerol (p < 0.05) and showed a trend towards higher lactate to pyruvate ratio (p = 0.08) in cerebral microdialysate as well as higher levels of S-100B (p < 0.05) in jugular venous plasma compared with medium-high tidal volume ventilation.ConclusionsContrary to the hypothesis, protective ventilation did not affect inflammatory cytokines. The low tidal volume group had increased cerebral blood flow, cerebral oxygen delivery and cerebral metabolism together with increased levels of markers of brain injury compared with medium-high tidal volume ventilation.

Dataset Information

Brain injury after 50 h of lung-protective mechanical ventilation in a preclinical model.

Publications

Brain injury after 50 h of lung-protective mechanical ventilation in a preclinical model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets