Oxygen-dependent reperfusion injury in the isolated rat lung

1992 ◽  
Vol 72 (4) ◽  
pp. 1454-1460 ◽  
Author(s):  
R. G. Eckenhoff ◽  
C. Dodia ◽  
Z. Tan ◽  
A. B. Fisher
Keyword(s):  
Electron Microscopy ◽  
Lipid Peroxidation ◽  
Lactate Dehydrogenase ◽  
Lung Injury ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Lung Model ◽  
Lung Damage ◽  
Rat Lung ◽  
Wet Weight

To further define the relationship between oxygen dependence of lung injury during ischemia and ischemia-reperfusion, we used the isolated, perfused, and ventilated rat lung model, so that oxygenation and perfusion could be separated. During ischemia, lungs were ventilated with various oxygen concentrations and then ventilated with 95% oxygen during the 60-min reperfusion period. Other lungs were ventilated with 0% oxygen (nitrogen) during ischemia, and the reperfusion phase oxygen concentration was varied. Tissue and perfusate lipid peroxidation products (thiobarbituric acid-reactive substances and conjugated dienes), dry-to-wet weight ratio, and lactate dehydrogenase were measured as indexes of lung damage. In addition, electron microscopy of some lungs was performed. Results demonstrate an oxygen dependence of lipid peroxidation in both the ischemic and reperfusion phases, but lipid peroxidation is severalfold greater in the reperfusion than in the ischemic phase. Products of lipid peroxidation closely correlate with indexes of lung injury (dry-to-wet weight ratio, lactate dehydrogenase, and electron microscopy).

Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury

2006 ◽  
Vol 291 (5) ◽  
pp. L1018-L1026 ◽  
Author(s):  
Minqing Zhao ◽  
Lucas G. Fernandez ◽  
Allan Doctor ◽  
Ashish K. Sharma ◽  
Alexander Zarbock ◽  
...  
Keyword(s):  
Lung Injury ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Lung Model ◽  
Mouse Lung ◽  
Chemokine Production ◽  
Cytokines And Chemokines ◽  
Tnf Α ◽  
Lung Dysfunction ◽  
The Impact

Lung ischemia-reperfusion (I/R) injury is a biphasic inflammatory process. Previous studies indicate that the later phase is neutrophil-dependent and that alveolar macrophages (AMs) likely contribute to the acute phase of lung I/R injury. However, the mechanism is unclear. AMs become activated and produce various cytokines and chemokines in many inflammatory responses, including transplantation. We hypothesize that AMs respond to I/R by producing key cytokines and chemokines and that depletion of AMs would reduce cytokine/chemokine expression and lung injury after I/R. To test this, using a buffer-perfused, isolated mouse lung model, we studied the impact of AM depletion by liposome-clodronate on I/R-induced lung dysfunction/injury and expression of cytokines/chemokines. I/R caused a significant increase in pulmonary artery pressure, wet-to-dry weight ratio, vascular permeability, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-2 expression, as well as decreased pulmonary compliance, when compared with sham lungs. After AM depletion, the changes in each of these parameters between I/R and sham groups were significantly attenuated. Thus AM depletion protects the lungs from I/R-induced dysfunction and injury and significantly reduces cytokine/chemokine production. Protein expression of TNF-α and MCP-1 are positively correlated to I/R-induced lung injury, and AMs are a major producer/initiator of TNF-α, MCP-1, and MIP-2. We conclude that AMs are an essential player in the initiation of acute lung I/R injury.

Apocynin attenuates ischemia-reperfusion lung injury in an isolated and perfused rat lung model

2011 ◽  
Vol 158 (1) ◽  
pp. 17-29 ◽  
Author(s):  
Chi-Huei Chiang ◽  
Chiao-Hui Chuang ◽  
Shiou-Ling Liu
Keyword(s):  
Lung Injury ◽  
Ischemia Reperfusion ◽  
Lung Model ◽  
Rat Lung

Ischemia-reperfusion lung injury: contribution of ischemia, neutrophils, and hydrostatic pressure

1997 ◽  
Vol 273 (1) ◽  
pp. L46-L54 ◽  
Author(s):  
Y. T. Lu ◽  
P. G. Hellewell ◽  
T. W. Evans
Keyword(s):  
Lung Injury ◽  
Ischemia Reperfusion ◽  
Lung Model ◽  
Ischemia And Reperfusion ◽  
Rat Lung ◽  
Significant Difference ◽  
Capillary Membranes ◽  
Early Injury ◽  
Smooth Muscle Relaxant ◽  
Alveolar Capillary

We used an isolated, blood-perfused rat lung model to evaluate the separate roles of ischemia and reperfusion time, the changes in pulmonary artery pressure (Ppa), and the circulating neutrophil number in mediating ischemia-reperfusion lung injury. Extravascular albumin accumulation was used to quantify changes in the permeability of the alveolar capillary membranes. In animals subjected to 30 and 45 min of ischemia without reperfusion, extravascular albumin accumulation was significantly higher than in controls subjected to continuous perfusion (P < 0.05). Albumin accumulation in animals subjected to 45 min of ischemia was greater compared with those undergoing 30 min of ischemia followed by 30 min of reperfusion (P < 0.05). In animals undergoing 45 min of ischemia followed by 30 min of reperfusion, a linear relationship was demonstrated between changes in Ppa and extravascular albumin accumulation. Reducing Ppa with a thromboxane antagonist (ICI-192605) and a smooth muscle relaxant (papaverine) produced, in both cases, a significant decrease in albumin extravasation (P < 0.05). No significant difference in extravascular albumin accumulation or change in Ppa was shown in neutrophil-depleted animals compared with nondepleted animals. We conclude that ischemia time contributes significantly to ischemia-reperfusion lung injury and that transient changes in Ppa after reperfusion exacerbate and injury in this model. This early injury demonstrated here was neutrophil dependent.

scholarly journals Ginsenoside Rb1 Treatment Attenuates Pulmonary Inflammatory Cytokine Release and Tissue Injury following Intestinal Ischemia Reperfusion Injury in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Ying Jiang ◽  
Zhen Zhou ◽  
Qing-tao Meng ◽  
Qian Sun ◽  
Wating Su ◽  
...  
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Weight Ratio ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Ginsenoside Rb1 ◽  
Intestinal Ischemia Reperfusion

Objective. Intestinal ischemia reperfusion (II/R) injury plays a critical role in remote organ dysfunction, such as lung injury, which is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In the present study, we tested whether ginsenoside Rb1 attenuated II/R induced lung injury by Nrf2/HO-1 pathway.Methods. II/R injury was induced in male C57BL/6J mice by 45 min of superior mesenteric artery (SMA) occlusion followed by 2 hours of reperfusion. Ginsenoside Rb1 was administrated prior to reperfusion with or without ATRA (all-transretinoic acid, the inhibitor of Nrf2/ARE signaling pathway) administration before II/R.Results. II/R induced lung histological injury, which is accompanied with increased levels of malondialdehyde (MDA), interleukin- (IL-) 6, and tumor necrosis factor- (TNF-)αbut decreased levels of superoxide dismutase (SOD) and IL-10 in the lung tissues. Ginsenoside Rb1 reduced lung histological injury and the levels of TNF-αand MDA, as well as wet/dry weight ratio. Interestingly, the increased Nrf2 and HO-1 expression induced by II/R in the lung tissues was promoted by ginsenoside Rb1 treatment. All these changes could be inhibited or prevented by ATRA.Conclusion. Ginsenoside Rb1 is capable of ameliorating II/R induced lung injuries by activating Nrf2/HO-1 pathway.

scholarly journals Dexmedetomidine Attenuates Lung Ischemia-reperfusion Injury in Rats by Reducing Mitochondrial Dysfunction

2020 ◽  
Author(s):  
Yan Zhang ◽  
Yao Lu ◽  
Kai Wang ◽  
Mei-yan Zhou ◽  
Cong-you Wu ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Reperfusion Injury ◽  
Mitochondrial Biogenesis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Oxygenation Index ◽  
Lung Damage ◽  
Peroxisome Proliferator ◽  
Sprague Dawley

Abstract Background: Lung ischemia-reperfusion injury (LIRI) is a significant clinical problem occurring after lung transplantation. LIRI is mediated by the overproduction of reactive oxygen species (ROS) and inflammatory activation. Previous studies have confirmed that dexmedetomidine (DEX) exerts a protective effect on LIRI, which potentially causes severe mitochondrial dysfunction. However, the specific mechanisms remain unclear. Our study was to explore whether dexmedetomidine exerts a beneficial effect on LIRI by reducing mitochondrial dysfunction. Methods: Two different models were used in our study. For the in vivo experiment, thirty-two male Sprague-Dawley rats were randomly divided into Sham, ischemia-reperfusion (I/R), DEX+I/R and DEX+yohimbine+I/R (DY+I/R) groups. Similarly, pulmonary vascular endothelial cells (PVECs) from SD rats were divided into Control, oxygen glucose deprivation (OGD), D+OGD and DY+OGD groups.Results: In our experiment, we confirmed severe lung damage after LIRI that was characterized by significantly pulmonary histopathology injury, a decrease in the oxygenation index (PaO2/FiO2) and an increase in the wet-to-dry weight ratio, while DEX treatment mitigated this damage. In addition, the DEX pretreatment significantly attenuated I/R-induced oxidative stress by decreasing the level of ROS in the mitochondria in vitro. Moreover, the DEX treatment enhanced mitochondrial biogenesis and autophagy by increasing the expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A (Tfam), PTEN-induced putative kinase 1 (PINK1), Parkin and dynamin 1-like protein 1 (Drp1). Conclusions: These data suggest that DEX may alleviate LIRI by reducing mitochondrial dysfunction through the induction of mitochondrial biogenesis and autophagy.

scholarly journals Mechanism of MCP-1 in Acute Lung Injury and Advanced Therapy by Drug-Loaded Dextrin Nanoparticle

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Zheng Cao ◽  
Jing-Lan Liu ◽  
Shen Wu ◽  
Qiao Wang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Weight Ratio ◽  
Blood Gas Analysis ◽  
Gas Analysis ◽  
Inflammatory Factors ◽  
Saline Control ◽  
Mrna Levels ◽  
Blood Gas ◽  
Wet Weight

Objective. To observe the expression of monocyte chemotactic protein 1 (MCP-1) in acute lung injury (ALI) rat model, to characterize its effect on the development and progression of ALI, and to identify the potential new drug delivery approach during in vivo experiment. Method. The effects of different doses of lipopolysaccharide (LPS) on human pulmonary artery endothelial cells (HPAEC) were tested. For the animal experiments, thirty Sprague-Dawley (SD) rats were divided into physiological saline control group (NC group), the LPS model group (L group), the antagonist RS102895 combined with LPS group (R + L group), and the antagonist RS102895-loaded polyaldehyde dextran nanoparticles combined with LPS group (DNPR + L group). The blood gas analysis and dry/wet weight ratio were detected 24 hours after interventions. The levels of inflammatory factors, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were tested by ELISA. The expression of monocyte chemoattractant protein-1 (MCP-1) in lung tissues was examined through Western blot, and the change of MCP-1 mRNA expression level was detected by performing RT-PCR. Result. LPS was responsible for inducing ALI in rats, and the degree of cell damage was dose-dependent. Blood gas analysis of L group showed that PaO2 and PaO2/FiO2 levels were significantly lower than those of the NC group (P<0.05), while the dry/wet weight ratio of lung tissues in L group increased (P<0.05). Inflammatory factors including TNF-α and IL-1β and the expression of MCP-1 in both protein and mRNA levels were higher in L group than in the NC group (P<0.05). The inhibition of the interaction between MCP-1 and chemokines receptor 2 (CCR2) by antagonist RS102895 can significantly alleviate the ALI in rats, which is accompanied by a significant decrease of inflammatory factors and MCP-1 expression (P<0.05). Compared with R + L group, treatment with DNPR and LPS combination significantly improved the condition of rats and decreased the level of TNF-α, IL-1β, and MCP-1 expression (P<0.05). Conclusion. In ALI, RS102895 can inhibit the MCP-1/CCR2 interaction, therefore, retarding the progress of ALI. Because of the high transfection efficiency of inhibitor RS102895packgaed by polyaldehyde dextran nanoparticles, this phenomenon particularly reached a significant level. The results imply new insights for the treatment of ALI.

scholarly journals Continuous Observation of Superoxide Generation in an In-Situ Ischemia - Reperfusion Rat Lung Model

2001 ◽  
Vol 65 (3) ◽  
pp. 207-212 ◽  
Author(s):  
Jun Midorikawa ◽  
Kazuhira Maehara ◽  
Hiroyuki Yaoita ◽  
Tatsuya Watanabe ◽  
Hiroshi Ohtani ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Lung Model ◽  
Rat Lung ◽  
Continuous Observation ◽  
Superoxide Generation

Protective Effect of Ginsenoside Rb1 Mixing with Several Lung Flush Solutions on Pulmonary Ischemia-Reperfusion Injury

2014 ◽  
Vol 884-885 ◽  
pp. 625-629
Author(s):  
Feng Wu Lin ◽  
Chuan Zhang ◽  
Qiang Zhang ◽  
Kun Peng Cheng ◽  
Nan Gao ◽  
...  
Keyword(s):  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Protective Effects ◽  
Ginsenoside Rb1 ◽  
Wet Weight ◽  
Pulmonary Ischemia ◽  
Dextran Solution

Objective: To evaluate the protective effects of ginsenoside Rb1 mixed with LPD compared to mixed with several other lung flush solutions on ischemia-reperfusion injury. Method: Three group of rabbit lungs were perfused with three kinds of mixtures of ginsenoside Rb1 with blood, Euro-Collins solution(EC) or low-potassium-dextran solution(LPD) respectively, then lung dry/wet weight ratio and malondiadehyde(MAD) were examined and histological changes were observed. Result: Lung dry/wet weight ratio of LPD and Rb1 group was higher than that of EC and Rb1 and blood and Rb1 groups, whereas MAD of LPD and Rb1 group was significantly less than that of EC and Rb1 and blood and Rb1 groups（P<0.05）. Histological findings showed less damage in LPD and Rb1 group. Conclusion: Ginsenoside Rb1 mixed with LPD shows a better protective effect on pulmonary ischemia-reperfusion injury compared with other mixtures.

A CD18 antibody prevents lung injury but not hypotension after intestinal ischemia-reperfusion

1993 ◽  
Vol 74 (2) ◽  
pp. 659-664 ◽  
Author(s):  
J. Hill ◽  
T. Lindsay ◽  
C. R. Valeri ◽  
D. Shepro ◽  
H. B. Hechtman
Keyword(s):  
Monoclonal Antibody ◽  
Lung Injury ◽  
Blood Cell ◽  
Cell Count ◽  
White Blood Cell Count ◽  
White Blood Cell ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Blood Cell Count

Antibodies to the neutrophil CD18 integrin have been shown to ameliorate the local effects of intestinal ischemia and reperfusion (I/R). In addition to local mucosal injury, intestinal I/R results in systemic hypotension and injury to the lungs with lung leukosequestration. This study tests the effect of a CD18 monoclonal antibody on the hypotension and lung injury after intestinal I/R. In anesthetized rabbits, the superior mesenteric artery was clamped for 60 min followed by 3 h of reperfusion. Animals were treated with saline, an anti-CD18 monoclonal antibody (R15.7 MAb), or nonspecific immunoglobulin G. Another non-ischemic group were sham controls. Neutrophil sequestration was assessed by measure of lung myeloperoxidase (MPO) and permeability by lung-to-blood concentration ratio of 125I-labeled bovine serum albumin and wet-to-dry weight ratio. Immediately after reperfusion, mean arterial pressure fell to 49 +/- 2.1 mmHg and remained at this level. The hypotension was unaffected by treatment with R15.7 MAb. Thirty minutes after reperfusion, the circulating white blood cell count fell to 2.91 +/- 0.53 x 10(3)/mm3 vs. sham 6.40 +/- 0.66 x 10(3)/mm3 (P < 0.05). Treatment with R15.7 MAb prevented this fall in white blood cell count (5.75 +/- 1.59 x 10(3)/mm3). At 3 h of reperfusion in saline-treated animals there was increased MPO, 74.8 +/- 4.9 U/g vs. 42.0 +/- 4.8 U/g in sham animals (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document