Animal models of acute lung injury

Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.

Download Full-text

Effects of acid aspiration-induced acute lung injury on kidney function

AJP Renal Physiology ◽

10.1152/ajprenal.00357.2007 ◽

2008 ◽

Vol 294 (4) ◽

pp. F900-F908 ◽

Cited By ~ 13

Author(s):

Jeffrey B. Hoag ◽

Manchang Liu ◽

R. Blaine Easley ◽

Martin F. Britos-Bray ◽

Priya Kesari ◽

...

Keyword(s):

Acute Lung Injury ◽

Animal Models ◽

Lung Injury ◽

Small Animal ◽

Kidney Injury ◽

Structure And Function ◽

Acid Aspiration ◽

Kidney Structure ◽

Small Animal Models ◽

And Function

Acute lung injury (ALI) in combination with acute kidney injury carries a mortality approaching 80% in the intensive care unit. Recently, attention has focused on the interaction of the lung and kidney in the setting of ALI and mechanical ventilation (MV). Small animal models of ALI and MV have demonstrated changes in inflammatory mediators, water channels, apoptosis, and function in the kidney early in the course of injury. The purpose of this investigation was to test the hypothesis that ALI and injurious MV cause early, measurable changes in kidney structure and function in a canine HCl aspiration model of ALI when hemodynamics and arterial blood gas tensions are carefully controlled. Intratracheal HCl induced profound ALI as demonstrated by increased shunt fraction and airway pressures compared with sham injury. Sham-injured animals had similar mean arterial pressure and arterial Pco2 and HCO3 levels compared with injured animals. Measurements of renal function including renal blood flow, urine flow, serum creatinine, glomerular filtration rate, urine albumin-to-creatinine ratio, and kidney histology scores were not different between groups. With maintenance of hemodynamic parameters and alveolar ventilation, ALI and injurious MV do not alter kidney structure and function early in the course of injury in this acid aspiration canine model. Kidney injury in large animal models may be more similar to humans and may differ from results seen in small animal models.

Download Full-text

Effects of Positive End-expiratory Pressure Titration and Recruitment Maneuver on Lung Inflammation and Hyperinflation in Experimental Acid Aspiration–induced Lung Injury

Anesthesiology ◽

10.1097/aln.0b013e31827542aa ◽

2012 ◽

Vol 117 (6) ◽

pp. 1322-1334 ◽

Cited By ~ 17

Author(s):

Aline M. Ambrosio ◽

Rubin Luo ◽

Denise T. Fantoni ◽

Claudia Gutierres ◽

Qin Lu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Lung Inflammation ◽

Recruitment Maneuver ◽

Alveolar Wall ◽

Arterial Oxygenation ◽

Positive End Expiratory Pressure ◽

Acid Aspiration ◽

Recruitment Maneuvers ◽

Alveolar Area

Background In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Methods Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Results Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. Conclusion In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.

Download Full-text

Corrigendum to: Acute Lung Injury in A Rat Model Of Intestinal Ischemia-Reperfusion: The Potential Time Depended Role Of Phospholipases

Journal of Surgical Research ◽

10.1016/j.jss.2021.03.032 ◽

2021 ◽

Vol 263 ◽

pp. 291

Author(s):

Georgia Kostopanagiotou ◽

Efthimios Avgerinos ◽

Konstantinos Kostopanagiotou ◽

Nikolaos Arkadopoulos ◽

Ioanna Andreadou ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Rat Model ◽

Intestinal Ischemia ◽

Ischemia Reperfusion ◽

Intestinal Ischemia Reperfusion

Download Full-text

Ischemic post-conditioning attenuates acute lung injury induced by intestinal ischemia–reperfusion in mice: role of Nrf2

Laboratory Investigation ◽

10.1038/labinvest.2016.87 ◽

2016 ◽

Vol 96 (10) ◽

pp. 1087-1104 ◽

Cited By ~ 15

Author(s):

Qing-Tao Meng ◽

Chen Cao ◽

Yang Wu ◽

Hui-Min Liu ◽

Wei Li ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Intestinal Ischemia ◽

Ischemia Reperfusion ◽

Intestinal Ischemia Reperfusion

Download Full-text

Acute Lung Injury: What Have We Learned from Animal Models?

The American Journal of the Medical Sciences ◽

10.1097/00000441-199308000-00010 ◽

1993 ◽

Vol 306 (2) ◽

pp. 111-116 ◽

Cited By ~ 23

Author(s):

A.C.J. Windsor ◽

P.G. Mullen ◽

A.A. Fowler

Keyword(s):

Acute Lung Injury ◽

Animal Models ◽

Lung Injury

Download Full-text

Analysis of Risk Factors Associated with Outcomes in Road Traffic Injury Patients with Acute Lung Injury

Journal of International Medical Research ◽

10.1177/147323000903700327 ◽

2009 ◽

Vol 37 (3) ◽

pp. 835-840

Author(s):

L Sheng ◽

J-S Wu ◽

M Zhang ◽

S-W Xu ◽

J-X Gan ◽

...

Keyword(s):

Risk Factors ◽

Acute Lung Injury ◽

Lung Injury ◽

Road Traffic ◽

Road Traffic Injury ◽

Apache Ii Score ◽

Factors Associated ◽

Traffic Injury ◽

Short And Long Term

Over 50% of road traffic injury (RTI) patients experience post-traumatic acute lung injury (ALI) and it is, therefore, extremely important to identify the risk factors related to the poor outcomes associated with ALI in RTI populations. This study evaluated 19 potential risk factors associated with the outcomes of ALI in 366 RTI patients. They were divided into two groups: a ‘favourable outcomes group’ and an ‘unfavourable outcomes group’. The results indicated that the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the presence of gastrointestinal haemorrhage may help predict the outcomes of ALI in the early post-trauma phase of treatment. The duration of trauma and sepsis were shown to impact strongly on both the short- and long-term outcomes of ALI. Age (≥ 65 years) and disseminated intravascular coagulation in the early RTI phase were also independent risk factors for a poorer short- and long-term outcome in ALI.

Download Full-text

Gut Lymph Purification in Rats With Acute Lung Injury Caused By Gut Ischemia Reperfusion Injury

10.21203/rs.3.rs-606735/v1 ◽

2021 ◽

Author(s):

Can Jin ◽

Shucheng Zhang ◽

Linlin Wu ◽

Bohan Li ◽

Meimei Shi ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Reperfusion Injury ◽

Lung Tissue ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Mononuclear Phagocyte ◽

Alveolar Epithelial Cells ◽

Expression Level ◽

Tissue Samples

Abstract Rationale: It is unclear whether removing the danger-associated molecular patterns (DAMPs) of gut lymph (GL) in the rats of gut ischemia-reperfusion injury (GIRI) model may reduce the distant organ lung injury.Objective: To determine whether oXiris gut lymph purification (GLP) may remove the DAMPs of GL in the rats’ model of acute lung injury (ALI) caused by GIRI.Methods: The experimental rats were divided into four groups: Sham group, GIRI group, GIRI + gut lymph drainage (GLD) group, and GIRI + GLP group. After successful modeling, the lung tissue samples of rats in each group were taken for hematoxylin-eosin (HE) staining and detection of expression levels of apoptotic indexes. The level of DAMPs was detected in blood and lymph. We observed its microstructure of type II alveolar epithelial cells (AECⅡ), and detected the expression level of apoptosis indexes.Measurements and Main Results: GIRI-induced destruction of alveolar structure, thickened alveolar walls, inflammatory cell infiltration emerged in the GIRI group, HMGB-1 and IL-6 levels significantly increased, and HSP70 and IL-10 levels reduced in lymph and serum. Compared with GIRI group, the lung tissue damage in GIRI + GLP group significantly improved, the expression level of HMGB-1 and IL-6 in the lymph and serum reduced, and HSP70 and IL-10 increased. The organelle structure of AECII in GIRI + GLP group was significantly improved compared with the GIRI group. Conclusions: oXiris GLP blocks the key link between DAMPs and mononuclear phagocyte system to inhibit inflammation and cell apoptosis, thereby reducing ALI induced by GIRI.

Download Full-text

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.

Download Full-text