Management of combined massive burn and blast injury: A 20-year experience

Zheng, Xianyou; Zhu, Feng; He, Fang; Xu, Dayuan; Xu, Long; Chen, Tiansheng; Zheng, Yongjun; Xiao, Shichu; Xia, Zhaofan

doi:10.1016/j.burns.2018.11.010

Cited by 15 publications

(7 citation statements)

References 14 publications

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“…(1) Thermal injury is an acceptable model to study the molecular mechanism behind the burn-induced heart dysfunction. However, the pathophysiological process of thermal injury in animal models is biased from burn patients in some aspects, for example, lung injury is an important characteristic in some burn patients with smoke inhalation ( 36 , 37 ). Therefore, these results do not firmly imply calpain 1 as a therapeutic target in burn patients.…”

Section: Discussionmentioning

confidence: 99%

Severe Burn-Induced Mitochondrial Recruitment of Calpain Causes Aberrant Mitochondrial Dynamics and Heart Dysfunction

Ranran

Zhang

Qiao

et al. 2023

Shock

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Mitochondrial damage is an important cause of heart dysfunction after severe burn injury. However, the pathophysiological process remains unclear. This study aims to examine the mitochondrial dynamics in the heart and the role of μ-calpain, a cysteine protease, in this scenario. Rats were subjected to severe burn injury treatment, and the calpain inhibitor MDL28170 was administered intravenously 1 h before or after burn injury. Rats in the burn group displayed weakened heart performance and decreased mean arterial pressure, which was accompanied by a diminishment of mitochondrial function. The animals also exhibited higher levels of calpain in mitochondria, as reflected by immunofluorescence staining and activity tests. In contrast, treatment with MDL28170 before any severe burn diminished these responses to a severe burn. Burn injury decreased the abundance of mitochondria and resulted in a lower percentage of small mitochondria and a higher percentage of large mitochondria. Furthermore, burn injury caused an increase in the fission protein DRP1 in the mitochondria and a decrease in the inner membrane fusion protein OPA1. Similarly, these alterations were also blocked by MDL28170. Of note, inhibition of calpain yielded the emergence of more elongated mitochondria along with membrane invagination in the middle of the longitude, which is an indicator of the fission process. Finally, MDL28170, administered 1 h after burn injury, preserved mitochondrial function and heart performance, and increased the survival rate. Overall, these results provided the first evidence that mitochondrial recruitment of calpain confers heart dysfunction after severe burn injury, which involves aberrant mitochondrial dynamics.

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Section: Discussionmentioning

confidence: 99%

Severe Burn-Induced Mitochondrial Recruitment of Calpain Causes Aberrant Mitochondrial Dynamics and Heart Dysfunction

Ranran

Zhang

Qiao

et al. 2023

Shock

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“…Severe burns are often accompanied by fatal complications, of which ALI is one of the earliest and most severe complication [ 1 , 2 , 44 ]. Mounting evidence indicates that PMVEC injury and the accumulation of ROS play an essential role in ALI development [ 7 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…Severe burn injury is a complex pathophysiological process that results in the dysfunction of multiple organs [ 1–3 ]. Acute lung injury (ALI) is one of the most critical side effects and is associated with high mortality, especially when the burn area exceeds 30% of the total body surface area (TBSA) [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species

Cai

Shen

et al. 2022

Burns &Amp; Trauma

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Background Acute lung injury (ALI) is a common complication following severe burns. The underlying mechanisms of ALI are incompletely understood; thus, available treatments are not sufficient to repair the lung tissue after ALI. Methods To investigate the relationship between the Notch pathway and burn-induced lung injury, we established a rat burn injury model by scalding and verified lung injury via lung injury evaluations, including hematoxylin and eosin (H&E) staining, lung injury scoring, bronchoalveolar lavage fluid and wet/dry ratio analyses, myeloperoxidase immunohistochemical staining and reactive oxygen species (ROS) accumulation analysis. To explore whether burn injury affects Notch1 expression, we detected the expression of Notch1 and Hes1 after burn injury. Then, we extracted pulmonary microvascular endothelial cells (PMVECs) and conducted Notch pathway inhibition and activation experiments, via a γ-secretase inhibitor (GSI) and OP9-DLL1 coculture, respectively, to verify the regulatory effect of the Notch pathway on ROS accumulation and apoptosis in burn-serum-stimulated PMVECs. To investigate the regulatory effect of the Notch pathway on ROS accumulation, we detected the expression of oxidative-stress-related molecules such as superoxide dismutase, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) 2, NOX4 and cleaved caspase-3. NOX4-specific small interfering RNA (siRNA) and the inhibitor GKT137831 were used to verify the regulatory effect of the Notch pathway on ROS via NOX4. Results We successfully established a burn model and revealed that lung injury, excessive ROS accumulation and an inflammatory response occurred. Notch1 detection showed that the expression of Notch1 was significantly increased after burn injury. In PMVECs challenged with burn serum, ROS and cell death were elevated. Moreover, when the Notch pathway was suppressed by GSI, ROS and cell apoptosis levels were significantly increased. Conversely, these parameters were reduced when the Notch pathway was activated by OP9-DLL1. Mechanistically, the inhibition of NOX4 by siRNA and GKT137831 showed that the Notch pathway reduced ROS production and cell apoptosis by downregulating the expression of NOX4 in PMVECs. Conclusions The Notch pathway reduced ROS production and apoptosis by downregulating the expression of NOX4 in burn-stimulated PMVECs. The Notch–NOX4 pathway may be a novel therapeutic target to treat burn-induced ALI.

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“…Primary blast injuries are a complex type of trauma resulting in damage to gas-containing organs such as the lungs. 24 The shock wave from detonations can lead to mild blast injury to the lungs owing to increased intrathoracic pressure or chemical/thermal damage, leading to acute inflammatory responses 25 with small artery reactive hyperemia and pulmonary capillary rupture. 26 Based on this information, we hypothesize that this lung injury may have resulted in the airway bleeding observed in the 2 groups, potentially because all rescuers were exposed to gases for 110 min, on average.…”

Section: Discussionmentioning

confidence: 99%

Arterial Blood Gas and Rotational Thromboelastometry Parameters in Healthy Rescuers Incidentally Exposed to Nitroglycerin, Nitrogen Compounds, and Combustion Products

Petrucci

Cofini

Pizzi³

et al. 2022

Wilderness & Environmental Medicine

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Introduction-Acute exposure to nitrogen compounds combined with a massive inhalation of air pollutants can influence respiratory and cardiovascular symptoms and coagulation abnormalities in accidentally exposed healthy adults during cave detonation operations.Methods-Italian alpine and cave rescuers widened a cave in the Abisso Luca Kralj in Trieste, Italy. Volunteers inside the cave were accidentally exposed to the fumes from an uncontrolled detonation of blasting gelatin microcharges. We performed a retrospective cohort study on the clinical data, arterial blood gas analysis, and rotational thromboelastometry parameters from the rescuers involved in the accident.Results-Ninety-three healthy rescuers were involved in the uncontrolled detonation: 47 volunteers handled a mixture of nitrogen compounds (blaster group), and 46 volunteers did not (nonblaster group). After the accident, statistically significant differences (P<0.05) in arterial blood gas values were observed between the groups, with a pattern of mild respiratory acidosis with hypercapnia in the nonblaster group and severe mixed acid-base disorder with hypoxia and hypercapnia in the blaster group. Mild hyperfibrinolysis was observed in 44 volunteers in the blaster group, as were associated bleeding symptoms in 34 volunteers; no significant coagulation modifications were recorded in the nonblaster group.Conclusions-Respiratory acidosis with hypoxia, hypercapnia, a compensatory metabolic response, and mild hyperfibrinolysis were probably related to the combined effect of nitrogen compounds and the inhaled toxic products of detonation. Therefore, each element exerts a determinant effect on promoting the biological toxicity of the others.

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Management of combined massive burn and blast injury: A 20-year experience

Cited by 15 publications

References 14 publications

Severe Burn-Induced Mitochondrial Recruitment of Calpain Causes Aberrant Mitochondrial Dynamics and Heart Dysfunction

Severe Burn-Induced Mitochondrial Recruitment of Calpain Causes Aberrant Mitochondrial Dynamics and Heart Dysfunction

The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species

Arterial Blood Gas and Rotational Thromboelastometry Parameters in Healthy Rescuers Incidentally Exposed to Nitroglycerin, Nitrogen Compounds, and Combustion Products

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