Chronic lung injury in preterm lambs: disordered pulmonary elastin deposition

1997 ◽  
Vol 272 (3) ◽  
pp. L452-L460 ◽  
Author(s):  
R. A. Pierce ◽  
K. H. Albertine ◽  
B. C. Starcher ◽  
J. F. Bohnsack ◽  
D. P. Carlton ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Tidal Volume ◽  
Mrna Expression ◽  
Lung Tissue ◽  
Prolonged Mechanical Ventilation ◽  
Morphological Development ◽  
Mechanically Ventilated ◽  
Alveolar Development

Prolonged mechanical ventilation of premature neonates is often associated with abnormal morphological development of the lung and chronic lung disease, sometimes called bronchopulmonary dysplasia (BPD). Impaired alveolar development is a hallmark of this disease. To better understand the effects of mechanical ventilation on lung elastin expression, we studied lung tissue from 10 preterm lambs (gestation = 125 days; term = 148 days) mechanically ventilated for 3-4 wk at a respirator rate of 20 breaths/min and tidal volume of 15 +/- 5 ml/kg (n = 5) or 60 breaths/min and tidal volume of 5 +/- 2 ml/kg (n = 5). Histopathology showed increased elastin accumulation and abnormal morphological development in the ventilated groups. Postmortem lung desmosine content was increased significantly in the 20 breaths/min group. Tropoelastin mRNA expression was increased in both ventilated groups. In situ hybridization localized increased tropoelastin mRNA expression to sites of accumulated elastin in extended alveolar walls with scant, attenuated secondary crests. Lung collagen content, as assessed by the amount of hydroxyproline in lung tissue, was similar to controls. These data suggest that excessive production and accumulation of elastin is associated with chronic lung injury from prolonged mechanical ventilation after premature birth.

Dynamic Changes in Respiratory Frequency/Tidal Volume May Predict Failures of Ventilatory Liberation in Patients on Prolonged Mechanical Ventilation and Normal Preliberation Respiratory Frequency/Tidal Volume Values

2012 ◽  
Vol 78 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Raeanna C. Adams ◽  
Oliver L. Gunter ◽  
Jonathan R. Wisler ◽  
Melissa L. Whitmill ◽  
James Cipolla ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Tidal Volume ◽  
Prolonged Mechanical Ventilation ◽  
Respiratory Frequency ◽  
Dynamic Changes ◽  
Mechanically Ventilated ◽  
Rapid Shallow Breathing Index ◽  
Shallow Breathing ◽  
Mean Time ◽  
Better Than

Rapid shallow breathing index (RSBI, respiratory frequency [f] divided by tidal volume [Vt]) has been used to prognosticate liberation from mechanical ventilation (LMV). We hypothesize that dynamic changes in RSBI predict failed LMV better than isolated RSBI measurements. We conducted a retrospective study of patients who were mechanically ventilated (MV) for longer than 72 hours. Failed LMV was defined as need for reinstitution of MV within 48 hours post-LMV. Ventilatory frequency (f) and Vt (liters) were serially recorded. The instantaneous RSBI (i-RSBI) was defined as f/Vt. Dynamic f/Vt ratio (d-RSBI) was defined as the ratio between two consecutive i-RSBI (f/Vt) measurements ([f2/Vt2]/[f1/Vt1]). RSBI Product (RSB-P) was defined as (i-RSBI 3 d-RSBI). Data from 32 patients were analyzed (Acute Physiology and Chronic Health Evaluation II 13.4, male 69%, mean age 57 years). Mean length of stay was 19.5 days (11.5 ventilator; 14.1 intensive care unit days). For LMV failures, mean time to reinstitution of invasive MV was 20.8 hours. All patients had pre-LMV i-RSBI less than 100. Failed LMVs had higher i-RSBI values (68.9, n = 18) than successful LMVs (44.2, n = 23, P < 0.01). Failures had higher d-RSBI (1.48) than successful LMVs (1.05, P < 0.04). The RSB-P was higher for failed LMVs (118) than for successful LMVs (48.8, P < 0.01) with failures having larger proportion of pre-LMV d-RSBI values greater than 1.5 (39.0 vs 10.7%, P < 0.03). Pre-LMV RSB-P may offer early prediction of failed LMV in patients on MV for longer than 72 hours despite normal pre-LMV i-RSBI. Divergence between RSB-P for successful and failed LMVs occurred earlier than i-RSBI divergence with a greater proportion of pre-LMV d-RSBI greater than 1.5 among failures.

scholarly journals Interaction between regional lung volumes and ventilator-induced lung injury in the normal and endotoxemic lung

2020 ◽  
Vol 318 (3) ◽  
pp. L494-L499 ◽  
Author(s):  
Seiha Yen ◽  
Melissa Preissner ◽  
Ellen Bennett ◽  
Stephen Dubsky ◽  
Richard Carnibella ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Tidal Volume ◽  
Lung Volumes ◽  
Mechanically Ventilated ◽  
Ventilator Induced Lung Injury ◽  
Computed Tomography Images ◽  
Gas Trapping ◽  
Regional Lung ◽  
The Relationship

Both overdistension and atelectasis contribute to lung injury and mortality during mechanical ventilation. It has been proposed that combinations of tidal volume and end-expiratory lung volume exist that minimize lung injury linked to mechanical ventilation. The aim of this study was to examine this at the regional level in the healthy and endotoxemic lung. Adult female BALB/c mice were injected intraperitoneally with 10 mg/kg lipopolysaccharide (LPS) in saline or with saline alone. Four hours later, mice were mechanically ventilated for 2 h. Regional specific end-expiratory volume (sEEV) and tidal volume (sVt) were measured at baseline and after 2 h of ventilation using dynamic high-resolution four-dimensional computed tomography images. The regional expression of inflammatory genes was quantified by quantitative PCR. There was a heterogenous response in regional sEEV whereby endotoxemia increased gas trapping at end-expiration in some lung regions. Within the healthy group, there was a relationship between sEEV, sVt, and the expression of Tnfa, where high Vt in combination with high EEV or very low EEV was associated with an increase in gene expression. In endotoxemia there was an association between low sEEV, particularly when this was combined with moderate sVt, and high expression of IL6. Our data suggest that preexisting systemic inflammation modifies the relationship between regional lung volumes and inflammation and that although optimum EEV-Vt combinations to minimize injury exist, further studies are required to identify the critical inflammatory mediators to assess and the effect of different injury types on the response.

scholarly journals Effects of high-tidal-volume mechanical ventilation on the expression of P2X7 receptor and inflammatory response in lung tissue of rats

2018 ◽  
Vol 16 ◽  
pp. 205873921879594
Author(s):  
Jia Jia ◽  
Hanyu Qin ◽  
Bin Zang
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Tidal Volume ◽  
Lung Tissue ◽  
Sham Group ◽  
Receptor Expression ◽  
High Tidal Volume ◽  
Caspase 1 ◽  
High Tidal Volume Ventilation ◽  
Volume Ventilation

Ventilator-induced lung injury is a severe complication mainly caused from mechanical ventilation (MV), associated with the upregulation of inflammation response. The mechanism still remains unclear. This study aims to explore the effects of pathological damage, neutrophil infiltration, expression of P2X7 receptor, and activation of Caspase-1 in lung tissue using a rat model. Sprague Dawley (SD) rats were randomly divided into sham group, conventional MV group, and high-tidal-volume ventilation group and fed with clean water and rat food. The sham group received tracheotomy without MV; conventional MV group was given 7 mL/kg tidal volume ventilation, and high-tidal-volume MV group was given 28 mL/kg tidal volume ventilation. All the rats were sacrificed after 4 h of ventilation or spontaneous breath. Lung wet/dry ratio was measured, and paraffin sections were prepared for pathological injury assessment and immunohistochemistry of P2X7 and myeloperoxidase levels. Lung homogenate was used for Western blot analysis of P2X7 receptor and Caspase-1 levels and real-time polymerase chain reaction (PCR) analysis of P2X7 gene expression level. Compared to sham group and conventional MV group, high-tidal-volume MV led to an increase in lung wet/dry ratio and histology score. High-tidal-volume ventilation also led to chemotaxis of neutrophils. The expression levels of protein and messenger RNA (mRNA) of P2X7 receptor were significantly upregulated. Cleaved-caspase-1 expression was also upregulated. All data provide the evidence that high-tidal-volume MV can lead to lung injury, neutrophils infiltration, and upregulation of cleaved-Caspase-1 level. This result may be related to the upregulation of P2X7 receptor expression.

scholarly journals Surfactant plus budesonide decreases lung and systemic inflammation in mechanically ventilated preterm sheep

2019 ◽  
Vol 316 (5) ◽  
pp. L888-L893 ◽  
Author(s):  
T. Brett Kothe ◽  
Matthew W. Kemp ◽  
Augusto Schmidt ◽  
Emily Royse ◽  
Fabrizio Salomone ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Systemic Inflammation ◽  
Lung Tissue ◽  
Lavage Fluid ◽  
Mechanically Ventilated ◽  
Physiological Variables ◽  
Lung Physiology ◽  
Blood Pressures ◽  
Oxide Synthase

Mechanical ventilation with normal tidal volumes (VT) causes lung and systemic inflammation in preterm sheep. Mechanical ventilation is associated with bronchopulmonary dysplasia (BPD) in preterm infants, and the addition of budesonide to surfactant decreases BPD in clinical trials. Budesonide with surfactant will decrease the lung injury from mechanical ventilation for 24 h in preterm sheep. Lambs at 126 ± 1 day gestational age were delivered and randomized to either: 1) surfactant (200 mg/kg) or 2) surfactant mixed with budesonide (0.25 mg/kg) before mechanical ventilation with VT of 7–8 ml/kg for 2, 6, or 24 h ( n = 6 or 7/group). Lung physiology and budesonide levels in the plasma and the lung were measured. Lung tissue, bronchoalveolar lavage fluid (BALF), liver, and brain tissues were evaluated for indicators of injury. High initial budesonide plasma levels of 170 ng/ml decreased to 3 ng/ml at 24 h. Lung tissue budesonide levels were less than 1% of initial dose by 24 h. Although physiological variables were generally similar, budesonide-exposed lambs required lower mean airway pressures, had higher hyperoxia responses, and had more stable blood pressures. Budesonide decreased proinflammatory mRNA in the lung, liver, and brain. Budesonide also decreased total protein and proinflammatory cytokines in BALF, and decreased inducible nitric oxide synthase activation at 24 h. In ventilated preterm lambs, most of the budesonide left the lung within 24 h. The addition of budesonide to surfactant improved physiology, decreased markers of lung injury, and decreased systemic responses in liver and brain.

scholarly journals Resolvin D1 Alleviates Ventilator-Induced Lung Injury in Mice by Activating PPARγ/NF-κB Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Haifa Xia ◽  
Jingxu Wang ◽  
Shujun Sun ◽  
Fuquan Wang ◽  
Yiyi Yang ◽  
...  
Keyword(s):  
Lung Injury ◽  
Protective Effect ◽  
Tidal Volume ◽  
Signaling Pathways ◽  
Lung Tissue ◽  
Fatty Acid Derivative ◽  
High Tidal Volume ◽  
Treatment Modalities ◽  
Resolvin D1 ◽  
Ventilator Induced Lung Injury

As one of the basic treatment modalities in the intensive care unit (ICU), mechanical ventilation can cause or aggravate acute lung injury or ventilator-induced lung injury (VILI). Resolvin D1 (RvD1) is an endogenous polyunsaturated fatty acid derivative with strong anti-inflammatory action. In this study, we explored if RvD1 possesses a protective effect on VILI. Mice were ventilated with high tidal volume (40 mL/kg, HVT) for 4 h and were then intraperitoneally administered RvD1 at the beginning of high tidal volume ventilation and given GW9662 (a PPAR-γ antagonist) intraperitoneally 30 min before ventilation. RvD1 attenuated VILI, as evidenced by improved oxygenation and reduced histological injury, compared with HVT -induced lung injury. Similarly, it could ameliorate neutrophil accumulation and production of proinflammatory cytokines in lung tissue. In contrast, the protective effect of RvD1 on lung tissue could be reversed by GW9662. RvD1 mitigated VILI by activating peroxisome proliferator-activated receptor gamma (PPAR-γ) and inhibiting nuclear factor-kappa B (NF-κB) signaling pathways in mice. In conclusion, RvD1 could reduce the inflammatory response in VILI by activating PPAR-γ and inhibiting NF-κB signaling pathways.

scholarly journals Redox Balance and Cellular Inflammation in the Diaphragm, Limb Muscles, and Lungs of Mechanically Ventilated Rats

2010 ◽  
Vol 112 (2) ◽  
pp. 384-394 ◽  
Author(s):  
Judith Marín-Corral ◽  
Leticia Martínez-Caro ◽  
José A. Lorente ◽  
Marta de Paula ◽  
Lara Pijuan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mechanical Ventilation ◽  
Lung Injury ◽  
Protein Adducts ◽  
Organ Injury ◽  
Mechanically Ventilated ◽  
Ventilator Induced Lung Injury ◽  
Cellular Inflammation ◽  
Cell Counts ◽  
Limb Muscles

Background High tidal volume (VT) mechanical ventilation was shown to induce organ injury other than lung injury and systemic inflammation in animal models of ventilator-induced lung injury. The authors aimed to explore whether high VT mechanical ventilation per se induces early oxidative stress and inflammation in the diaphragm, limb muscles, and lungs of healthy rats exposed to ventilator-induced lung injury. Methods Protein carbonylation and nitration, antioxidants (immunoblotting), and inflammation (immunohistochemistry) were evaluated in the diaphragm, gastrocnemius, soleus, tibialis anterior, and lungs of mechanically ventilated healthy rats and in nonventilated control animals (n = 8/group) for 1 h, using two different strategies (moderate VT [VT = 9 ml/kg] and high VT [VT = 35 ml/kg]). Results The main findings are summarized as follows: compared with controls, (1) the diaphragms and gastrocnemius of high-VT rats exhibited a decrease in reactive carbonyls, (2) the soleus and tibialis of high- and moderate-VT rodents showed a reduction in reactive carbonyls and malondialdehyde-protein adducts, (3) the lungs of high-VT rats exhibited a significant rise in malondialdehyde-protein adducts, (4) the soleus and tibialis of both high- and moderate-VT rats showed a reduction in protein nitration, (5) the lungs of high- and moderate-VT rats showed a reduction in antioxidant enzyme levels, but not in the muscles, and (6) the diaphragms and gastrocnemius of all groups exhibited very low inflammatory cell counts, whereas the lungs of high-VT rats exhibited a significant increase in inflammatory infiltrates. Conclusions Although oxidative stress and inflammation increased in the lungs of rats exposed to high VT, the diaphragm and limb muscles exhibited a decline in oxidative stress markers and very low levels of cellular inflammation.

Weaning Analgosedation in Patients Requiring Prolonged Mechanical Ventilation

2021 ◽  
pp. 088506662110487
Author(s):  
Stephanie Parks Taylor ◽  
John M. Hammer ◽  
Brice T. Taylor
Keyword(s):  
Mechanical Ventilation ◽  
Prolonged Mechanical Ventilation ◽  
Multidisciplinary Care ◽  
Potential Harm ◽  
Mechanically Ventilated ◽  
Multidisciplinary Care Team ◽  
Clinical Trial Evidence ◽  
Adults And Children ◽  
Trial Evidence

Although research supports the minimization of sedation in mechanically ventilated patients, many patients with severe acute respiratory distress syndrome (ARDS) receive prolonged opioid and sedative infusions. ICU teams face the challenge of weaning these medications, balancing the risks of sedation with the potential to precipitate withdrawal symptoms. In this article, we use a clinical case to discuss our approach to weaning analgosedation in patients recovering from long-term mechanical ventilation. We believe that a protocolized, multimodal weaning strategy implemented by a multidisciplinary care team is required to reduce potential harm from both under- and over-sedation. At present, there is no strong randomized clinical trial evidence to support a particular weaning strategy in adult ICU patients, but appraisal of the existing literature in adults and children can guide decision-making to enhance the recovery of these patients.

scholarly journals Management of hypercapnia in critically ill mechanically ventilated patients—A narrative review of literature

2020 ◽  
Vol 21 (4) ◽  
pp. 327-333
Author(s):  
Ravindranath Tiruvoipati ◽  
Sachin Gupta ◽  
David Pilcher ◽  
Michael Bailey
Keyword(s):  
Mechanical Ventilation ◽  
Tidal Volume ◽  
Dead Space ◽  
Hypercapnic Acidosis ◽  
Mechanically Ventilated ◽  
Mechanically Ventilated Patients ◽  
Low Tidal Volume ◽  
Volume Ventilation ◽  
Low Volume ◽  
Ventilated Patients

The use of lower tidal volume ventilation was shown to improve survival in mechanically ventilated patients with acute lung injury. In some patients this strategy may cause hypercapnic acidosis. A significant body of recent clinical data suggest that hypercapnic acidosis is associated with adverse clinical outcomes including increased hospital mortality. We aimed to review the available treatment options that may be used to manage acute hypercapnic acidosis that may be seen with low tidal volume ventilation. The databases of MEDLINE and EMBASE were searched. Studies including animals or tissues were excluded. We also searched bibliographic references of relevant studies, irrespective of study design with the intention of finding relevant studies to be included in this review. The possible options to treat hypercapnia included optimising the use of low tidal volume mechanical ventilation to enhance carbon dioxide elimination. These include techniques to reduce dead space ventilation, and physiological dead space, use of buffers, airway pressure release ventilation and prone positon ventilation. In patients where hypercapnic acidosis could not be managed with lung protective mechanical ventilation, extracorporeal techniques may be used. Newer, minimally invasive low volume venovenous extracorporeal devices are currently being investigated for managing hypercapnia associated with low and ultra-low volume mechanical ventilation.

scholarly journals Desflurane Attenuates Ventilator-Induced Lung Injury in Rats with Acute Respiratory Distress Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Xue Lin ◽  
Ying-nan Ju ◽  
Wei Gao ◽  
Dong-mei Li ◽  
Chang-chun Guo
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Tidal Volume ◽  
Lung Tissue ◽  
Rat Model ◽  
Distress Syndrome ◽  
Inflammatory Factors ◽  
Ventilator Induced Lung Injury

Ventilator-induced lung injury aggravates the existing lung injury. This study investigated the effect of desflurane on VILI in a rat model of acute respiratory distress syndrome. Forty-eight rats were randomized into a sham (S) group, control (C) group, lipopolysaccharide/ventilation (LV) group, lipopolysaccharide/ventilation/desflurane (LVD) group, or lipopolysaccharide/low ventilation with and without desflurane (LLV and LLVD) groups. Rats in the S group received anesthesia only. Rats in the LV and LVD groups received lipopolysaccharide and were ventilated with a high tidal volume. Rats in LLV and LLVD groups were treated as the LV and LVD groups and ventilated with a low tidal volume. PaO2/FiO2, lung wet-to-dry weight ratios, concentrations of inflammatory factors in serum and BALF, histopathologic analysis of lung tissue, and levels of nuclear factor- (NF-) κB protein in lung tissue were investigated. PaO2/FiO2 was significantly increased by desflurane. Total cell count, macrophages, and neutrophils in BALF and proinflammatory factors in BALF and serum were significantly decreased by desflurane, while IL-10 was increased. The histopathological changes and levels of NF-κB protein in lung tissue were decreased by desflurane. The results indicated that desflurane ameliorated VILI in a rat model of acute respiratory distress syndrome.

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