Mechanical Ventilation and the Titer of Antibodies as Risk Factors for the Development of Transfusion-Related Lung Injury

Purpose. Onset of transfusion-related acute lung injury (TRALI) is suggested to be a threshold-event. Data is lacking on the relation between titer of antibodies infused and onset of TRALI. We determined whether onset of TRALI is dependent on the titer of MHC-I antibodies infused in a combined model of ventilator-induced lung injury and antibody-induced TRALl.Methods. BALB/c mice were ventilated for five hours with low (7.5 ml/kg) or high (15 ml/kg) tidal volume. After three hours of MV, TRALI was induced by infusion of 0.5 mg/kg, 2.0 mg/kg or 4.5 mg/kg MHC-I antibodies. Control animals received vehicle. After five hours of MV, animals were sacrificed.Results. MV with high tidal volumes resulted in increased levels of all markers of lung injury compared to animals ventilated with low tidal MV. In ventilator-induced lung injury, infusion of 4.5 mg/kg of antibodies further increased pulmonary wet-to-dry ratio, pulmonary neutrophil influx and pulmonary KC levels, whereas infusion of lower dose of antibodies did not augment lung injury. In contrast, mice ventilated with low tidal volumes did not develop lung injury, irrespective of the dose of antibody used.Conclusions. In the presence of injurious MV, onset of TRALI depends on the titer of antibodies infused.

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Risk Factors for Transfusion-Related Acute Lung Injury in Critical Patients Admitted in Intensive Care Unit: A Systematic Review and Meta-Analysis

10.21203/rs.3.rs-52231/v1 ◽

2020 ◽

Author(s):

Lunyang Hu ◽

Baoli Wang ◽

Yong Jiang ◽

Banghui Zhu ◽

Chen Wang ◽

...

Keyword(s):

Risk Factors ◽

Mechanical Ventilation ◽

Acute Lung Injury ◽

Blood Transfusion ◽

Lung Injury ◽

Chronic Alcohol ◽

Related Factors ◽

Chronic Alcohol Abuse ◽

Related Risk ◽

Critical Patients

Abstract Background: Until now, transfusion-related acute lung injury (TRALI) has been considered to be the leading cause of blood transfusion-related diseases and death. And there is no clinically effective treatment plan for TRALI. The aim of this study was to systematically summarize the literature on risk factors for TRALI in critical patients. Methods: Electronic searches (up to March 2020) were performed in the Cochrane Library, Web of Knowledge, Embase, and PubMed databases. We included studies reporting on the risk factors of TRALI for critical patients and extracted the risk factors. Finally, third studies met the inclusion criteria. Results: We summarized and analyzed the potential risk factors of TRALI for critical patients in 13 existing studies. The host-related factors were age (odds ratio (OR) [95% confidence interval] = 1.16 [1.08-1.24]), sex (OR = 1.26 [1.16-1.38]), tobacco use status (OR = 3.82 [1.91-7.65]), chronic alcohol abuse (OR = 3.82 [2.97-26.83]), fluid balance (OR = 1.24 [1.08-1.42]), shock before transfusion (OR = 4.41 [2.38-8.20]), and ASA score of the recipients (OR = 2.72 [1.43-5.16]). The transfusion-related factors were the number of transfusions (OR = 1.40 [1.14-1.72]) and fresh frozen plasma (FFP) units (OR = 1.21 [1.01-1.46]). The device-related factor was mechanical ventilation (OR = 4.13 [2.20-7.76]). Conclusions: The risk factors for TRALI in this study included age, sex, tobacco use, chronic alcohol abuse, fluid balance, shock before transfusion, ASA score, number of transfusions, FFP units and mechanical ventilation. Our study suggests that host-related risk factors play a more important role in the occurrence and development of TRALI than blood transfusion-related risk factors.

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Efficacy of Low Tidal Volume Ventilation in Patients with Different Clinical Risk Factors for Acute Lung Injury and the Acute Respiratory Distress Syndrome

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/ajrccm.164.2.2011093 ◽

2001 ◽

Vol 164 (2) ◽

pp. 231-236 ◽

Cited By ~ 212

Author(s):

MARK D. EISNER ◽

TAYLOR THOMPSON ◽

LEONARD D. HUDSON ◽

JOHN M. LUCE ◽

DOUGLAS HAYDEN ◽

...

Keyword(s):

Risk Factors ◽

Acute Respiratory Distress Syndrome ◽

Acute Lung Injury ◽

Lung Injury ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Tidal Volume ◽

Distress Syndrome ◽

Low Tidal Volume ◽

Volume Ventilation

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Effects of MMP-9 inhibition by doxycycline on proteome of lungs in high tidal volume mechanical ventilation-induced acute lung injury

Proteome Science ◽

10.1186/1477-5956-8-3 ◽

2010 ◽

Vol 8 (1) ◽

pp. 3 ◽

Cited By ~ 11

Author(s):

Adrian Doroszko ◽

Thomas S Hurst ◽

Dorota Polewicz ◽

Jolanta Sawicka ◽

Justyna Fert-Bober ◽

...

Keyword(s):

Mechanical Ventilation ◽

Acute Lung Injury ◽

Lung Injury ◽

Tidal Volume ◽

High Tidal Volume

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Inhibition of Poly(Adenosine Diphosphate–Ribose) Polymerase Attenuates Ventilator-induced Lung Injury

Anesthesiology ◽

10.1097/01.anes.0000299434.86640.15 ◽

2008 ◽

Vol 108 (2) ◽

pp. 261-268 ◽

Cited By ~ 37

Author(s):

Rosanna Vaschetto ◽

Jan W. Kuiper ◽

Shyh Ren Chiang ◽

Jack J. Haitsma ◽

Jonathan W. Juco ◽

...

Keyword(s):

Mechanical Ventilation ◽

Lung Injury ◽

Tidal Volume ◽

Interleukin 6 ◽

Inflammatory Responses ◽

Adenosine Diphosphate ◽

High Tidal Volume ◽

Positive End Expiratory Pressure ◽

Ventilator Induced Lung Injury ◽

Pharmacologic Inhibition

Background Mechanical ventilation can induce organ injury associated with overwhelming inflammatory responses. Excessive activation of poly(adenosine diphosphate-ribose) polymerase enzyme after massive DNA damage may aggravate inflammatory responses. Therefore, the authors hypothesized that the pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase by PJ-34 would attenuate ventilator-induced lung injury. Methods Anesthetized rats were subjected to intratracheal instillation of lipopolysaccharide at a dose of 6 mg/kg. The animals were then randomly assigned to receive mechanical ventilation at either low tidal volume (6 ml/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (15 ml/kg) with zero positive end-expiratory pressure, in the presence and absence of intravenous administration of PJ-34. Results The high-tidal-volume ventilation resulted in an increase in poly(adenosine diphosphate-ribose) polymerase activity in the lung. The treatment with PJ-34 maintained a greater oxygenation and a lower airway plateau pressure than the vehicle control group. This was associated with a decreased level of interleukin 6, active plasminogen activator inhibitor 1 in the lung, attenuated leukocyte lung transmigration, and reduced pulmonary edema and apoptosis. The administration of PJ-34 also decreased the systemic levels of tumor necrosis factor alpha and interleukin 6, and attenuated the degree of apoptosis in the kidney. Conclusion The pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase reduces ventilator-induced lung injury and protects kidney function.

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Mechanosensitive cation channel Piezo1 contributes to ventilator-induced lung injury by activating RhoA/ROCK1 in rats

Respiratory Research ◽

10.1186/s12931-021-01844-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yang Zhang ◽

Lulu Jiang ◽

Tianfeng Huang ◽

Dahao Lu ◽

Yue Song ◽

...

Keyword(s):

Mechanical Ventilation ◽

Lung Injury ◽

Tidal Volume ◽

Cyclic Stretch ◽

High Tidal Volume ◽

Enzyme Linked Immunosorbent Assay ◽

Sprague Dawley ◽

Ventilator Induced Lung Injury ◽

Enhanced Expression ◽

Underlying Mechanisms

Abstract Background Mechanical ventilation can induce or aggravate lung injury, which is termed ventilator-induced lung injury (VILI). Piezo1 is a key element of the mechanotransduction process and can transduce mechanical signals into biological signals by mediating Ca2+ influx, which in turn regulates cytoskeletal remodeling and stress alterations. We hypothesized that it plays an important role in the occurrence of VILI, and investigated the underlying mechanisms. Methods High tidal volume mechanical ventilation and high magnitude cyclic stretch were performed on Sprague–Dawley rats, and A549 and human pulmonary microvascular endothelial cells, respectively, to establish VILI models. Immunohistochemical staining, flow cytometry, histological examination, enzyme-linked immunosorbent assay, western blotting, quantitative real-time polymerase chain reaction and survival curves were used to assess the effect of Piezo1 on induction of lung injury, as well as the signaling pathways involved. Results We observed that Piezo1 expression increased in the lungs after high tidal volume mechanical ventilation and in cyclic stretch-treated cells. Mechanistically, we observed the enhanced expression of RhoA/ROCK1 in both cyclic stretch and Yoda1-treated cells, while the deficiency or inhibition of Piezo1 dramatically antagonized RhoA/ROCK1 expression. Furthermore, blockade of RhoA/ROCK1 signaling using an inhibitor did not affect Piezo1 expression. GSMTx4 was used to inhibit Piezo1, which alleviated VILI-induced pathologic changes, water content and protein leakage in the lungs, and the induction of systemic inflammatory mediators, and improved the 7-day mortality rate in the model rats. Conclusions These findings indicate that Piezo1 affects the development and progression of VILI through promotion of RhoA/ROCK1 signaling.

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Activation of calpains mediates early lung neutrophilic inflammation in ventilator-induced lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00349.2011 ◽

2012 ◽

Vol 302 (4) ◽

pp. L370-L379 ◽

Cited By ~ 24

Author(s):

Dejie Liu ◽

Zhibo Yan ◽

Richard D. Minshall ◽

David E. Schwartz ◽

Yuguo Chen ◽

...

Keyword(s):

Mechanical Ventilation ◽

Lung Injury ◽

Tidal Volume ◽

Lung Inflammation ◽

Inflammatory Responses ◽

Neutrophil Recruitment ◽

Calpain Activation ◽

Ventilator Induced Lung Injury ◽

Volume Ventilation ◽

Calpain 2

Lung inflammatory responses in the absence of infection are considered to be one of primary mechanisms of ventilator-induced lung injury. Here, we determined the role of calpain in the pathogenesis of lung inflammation attributable to mechanical ventilation. Male C57BL/6J mice were subjected to high (28 ml/kg) tidal volume ventilation for 2 h in the absence and presence of calpain inhibitor I (10 mg/kg). To address the isoform-specific functions of calpain 1 and calpain 2 during mechanical ventilation, we utilized a liposome-based delivery system to introduce small interfering RNAs targeting each isoform in pulmonary vasculature in vivo. Mechanical ventilation with high tidal volume induced rapid (within minutes) and persistent calpain activation and lung inflammation as evidenced by neutrophil recruitment, production of TNF-α and IL-6, pulmonary vascular hyperpermeability, and lung edema formation. Pharmaceutical calpain inhibition significantly attenuated these inflammatory responses caused by lung hyperinflation. Depletion of calpain 1 or calpain 2 had a protective effect against ventilator-induced lung inflammatory responses. Inhibition of calpain activity by means of siRNA silencing or pharmacological inhibition also reduced endothelial nitric oxide (NO) synthase (NOS-3)-mediated NO production and subsequent ICAM-1 phosphorylation following high tidal volume ventilation. These results suggest that calpain activation mediates early lung inflammation during ventilator-induced lung injury via NOS-3/NO-dependent ICAM-1 phosphorylation and neutrophil recruitment. Inhibition of calpain activation may therefore provide a novel and promising strategy for the prevention and treatment of ventilator-induced lung injury.

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Alveolar macrophages contribute to alveolar barrier dysfunction in ventilator-induced lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00055.2006 ◽

2006 ◽

Vol 291 (6) ◽

pp. L1191-L1198 ◽

Cited By ~ 104

Author(s):

James A. Frank ◽

Charlie M. Wray ◽

Danny F. McAuley ◽

Reto Schwendener ◽

Michael A. Matthay

Keyword(s):

Mechanical Ventilation ◽

Epithelial Cell ◽

Lung Injury ◽

Tidal Volume ◽

Alveolar Macrophage ◽

Alveolar Macrophages ◽

Macrophage Activation ◽

Alveolar Epithelial Cell ◽

Alveolar Epithelial ◽

Ventilator Induced Lung Injury

In patients requiring mechanical ventilation for acute lung injury or acute respiratory distress syndrome (ARDS), tidal volume reduction decreases mortality, but the mechanisms of the protective effect have not been fully explored. To test the hypothesis that alveolar macrophage activation is an early and critical event in the initiation of ventilator-induced lung injury (VILI), rats were ventilated with high tidal volume (HVT) for 10 min to 4 h. Alveolar macrophage counts in bronchoalveolar lavage (BAL) fluid decreased 45% by 20 min of HVT( P < 0.05) consistent with activation-associated adhesion. Depletion of alveolar macrophages in vivo with liposomal clodronate significantly decreased permeability and pulmonary edema following 4 h of HVT( P < 0.05). BAL fluid from rats exposed to 20 min of HVTincreased nitric oxide synthase activity nearly threefold in naïve primary alveolar macrophages ( P < 0.05) indicating that soluble factors present in the air spaces contribute to macrophage activation in VILI. Media from cocultures of alveolar epithelial cell monolayers and alveolar macrophages exposed to 30 min of stretch in vitro also significantly increased nitrite production in naïve macrophages ( P < 0.05), but media from stretched alveolar epithelial cells or primary alveolar macrophages alone did not, suggesting alveolar epithelial cell-macrophage interaction was required for the subsequent macrophage activation observed. These data demonstrate that injurious mechanical ventilation rapidly activates alveolar macrophages and that alveolar macrophages play an important role in the initial pathogenesis of VILI.

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Mechanosensitive Cation Channel Piezo1 Contributes To Ventilator-Induced Lung Injury By Activating RhoA/ROCK1 In Rats

10.21203/rs.3.rs-555235/v1 ◽

2021 ◽

Author(s):

Yang Zhang ◽

Lulu Jiang ◽

Tianfeng Huang ◽

Dahao Lu ◽

Yue Song ◽

...

Keyword(s):

Mechanical Ventilation ◽

Lung Injury ◽

Tidal Volume ◽

Cyclic Stretch ◽

High Tidal Volume ◽

Enzyme Linked Immunosorbent Assay ◽

Sprague Dawley ◽

Reverse Transcription Pcr ◽

Ventilator Induced Lung Injury ◽

Underlying Mechanisms

Abstract Background: Mechanical ventilation can induce or aggravate lung injury, which is termed ventilator‑induced lung injury. Piezo1 is a key element of the mechanotransduction process and can transduce mechanical signals into biological signals by mediating Ca2+ influx, which in turn regulates cytoskeletal remodeling and stress alterations. We hypothesized that it plays an important role in the occurrence of ventilator‑induced lung injury, and we investigated the underlying mechanisms. Methods: High tidal volume mechanical ventilation and high magnitude cyclic stretch were performed on Sprague Dawley rats, and A549 and human pulmonary microvascular endothelial cells, respectively, to establish ventilator‑induced lung injury models. Immunohistochemical staining, flow cytometry, histological examination, enzyme-linked immunosorbent assay, western blotting, quantitative real-time reverse transcription-PCR and survival curves were used to assess the effect of Piezo1 on induction of lung injury, as well as the signaling pathways involved.Results: We observed that Piezo1 expression increased in the lungs after high tidal volume mechanical ventilation and in cyclic stretch-treated cells. Mechanistically, we observed the enhanced expression of RhoA/ROCK1 in both cyclic stretch and Yoda1-treated cells, while the deficiency or inhibition of Piezo1 dramatically antagonized RhoA/ROCK1 expression. Furthermore, blockade of RhoA/ROCK1 signaling using an inhibitor did not affect Piezo1 expression. GSMTx4 was used to inhibit Piezo1, which alleviated ventilator‑induced lung injury-induced pathologic changes, water content and protein leakage in the lungs, and the induction of systemic inﬂammatory mediators, and improved the 7-day mortality rate in the model rats. Conclusions: These findings indicate that Piezo1 affects the development and progression of ventilator‑induced lung injury through promotion of RhoA/ROCK1 signaling.

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