bims-heshmo 2021-10-17 papers

bims-heshmo

Biomed News

on Trauma hemorrhagic shock — molecular basis

Issue of 2021–10–17
eight papers selected by
Andreia Luís, Ludwig Boltzmann Institute

The Characteristics of Organ Function Damage of Hemorrhagic Shock in Hot Environment and The Effect of Hypothermic Fluid Resuscitation.
Analysis of polymorphonuclear cell apoptosis and inflammatory cytokines in trauma patients in the emergency department.
Sesamin Protects against and Ameliorates Rat Intestinal Ischemia/Reperfusion Injury with Involvement of Activating Nrf2/HO-1/NQO1 Signaling Pathway.
Polymorphonuclear myeloid-derived suppressor cells link inflammation and damage response after trauma.
Activation of transient receptor potential vanilloid 4 exacerbates myocardial ischemia-reperfusion injury via JNK-CaMKII phosphorylation pathway in isolated mice hearts.
A simple improvised prehospital method to warm intravenous fluid.
Phosphoinositide-3-kinase/Akt-endothelial nitric oxide synthase signaling pathway mediates the neuroprotective effect of sevoflurane postconditioning in a rat model of hemorrhagic shock and resuscitation.
The recipe for TACO: A narrative review on the pathophysiology and potential mitigation strategies of transfusion-associated circulatory overload.

Shock. 2021 Oct 08.

The Characteristics of Organ Function Damage of Hemorrhagic Shock in Hot Environment and The Effect of Hypothermic Fluid Resuscitation.

Yu Zhu, Sheng Ma, Hao-Yue Deng, Yue Wu, Jie Zhang, Xin-Ming Xiang, Xiao-Yong Peng, Liang-Ming Liu, Tao Li.

BACKGROUND: Hemorrhagic shock is the important factor for causing death of trauma and war injuries. However, pathophysiological characteristics and underlying mechanism in hemorrhagic shock with hot environment remain unclear.
METHODS: Hemorrhagic shock in hot environment rat model was used to explore the changes of mitochondrial and vital organ functions, the variation of the internal environment, stress factors, and inflammatory factors; meanwhile, the suitable treatment was further studied.
RESULTS: Above 36°C hot environment induced the increase of core temperature of rats, and the core temperature was not increased in 34°C hot environment, but the 34°C hot environment aggravated significantly hemorrhagic shock induced mortality. Further study showed that the mitochondrial functions of heart, liver, and kidney were more damaged in hemorrhagic shock rats with 34°C hot environment as compared with room environment. Moreover, the results showed that in hemorrhagic shock rats with hot environment, the blood concentration of Na+, K+, and plasma osmotic pressure, the expression of inflammatory factors tumor necrosis factor-α and interleukin-6 in the serum, as well as the stress factors Adrenocorticotropic Hormone and Glucocorticoid were all notably enhanced; and acidosis was more serous; oxygen supply and oxygen consumption were remarkably decreased. In addition, the present study demonstrated that mild hypothermia (10°C) fluid resuscitation could significantly improve the survival rate in hemorrhagic shock rats with hot environment as compared with normal temperature fluid resuscitation.
CONCLUSIONS: Hot environment accelerated the death of hemorrhagic shock rats, which was related to the disorder of internal environment, the increase of inflammatory and stress factors. Furthermore, moderate hypothermic (10°C) fluid resuscitation was suitable for the treatment of hemorrhagic shock in hot environment.

DOI: https://doi.org/10.1097/SHK.0000000000001873
Am J Transl Res. 2021 ;13(9): 10617-10624

Analysis of polymorphonuclear cell apoptosis and inflammatory cytokines in trauma patients in the emergency department.

Sung-Hyuk Choi, Jung-Youn Kim, Young-Hoon Yoon.

INTRODUCTION: Durring the immune-inflammation cascade in trauma patients, the roles of polymorphonuclear cells (PMNs) and inflammatory cytokines are very important; however, there is little research in this area, especially for patients with multiple traumas. This study aimed to determine the effects of inflammatory cytokines and apoptosis of PMNs on the prognosis of patients with multiple traumas in tertiary medical centers.
MATERIALS AND METHODS: The study subjects were patients with multiple severe traumas who had visited the emergency department. More specifically, patients with multiple traumas included those who had visited the emergency department because of trauma and presented with trauma in more than two body regions. The severity of the traumas was evaluated using the Glasgow coma scale (GCS) and abbreviated injury scale (AIS). In addition, prognostic factors including the length of the hospital stay in the intensive care unit (ICU), the condition upon discharge from the emergency department (discharge, hospitalization in a general ward, hospitalization in the intensive care unit, transfer to a different hospital, surgical operation, death, etc.), outcome of the surgical operation, and presence of infection were examined. To examine the inflammatory response factors, blood samples were obtained. Flow cytometry was performed to analyze PMN cell apoptosis. For comparative analysis, the patients were categorized according to their admission type and the presence of hemorrhagic shock.
RESULTS: Ninety-six patients were enrolled in the study (mean age 51.4 ± 16.7 years). When inpatients that had been admitted to the ICU were compared with general-ward inpatients, apoptosis, ROS, MIF, TNF-α, and IL-6 levels were found to be higher, with levels of TNF-α showing a statistically significant difference (726.7 ± 1524.2 vs. 37.5 ± 83.0, P = 0.037). PMN cell apoptosis was rarely observed in shock patients compared with non-shock patients (5.1 ± 5.8 vs. 15.0 ± 26.1, P = 0.004). When subjects were classified based on AIS (11 points or more, no more than 11 points), no significant differences were found between groups.
CONCLUSION: Findings of laboratory tests targeting trauma patients who required hospitalization showed that levels of inflammatory cytokines such as TNF-α were increased in ICU-hospitalized patients. PMN cell apoptosis was reduced according to the initial laboratory data of patients with hemorrhagic shock in the emergency department.

Keywords: PMN; Trauma; apoptosis; cytokines; inflammation
Oxid Med Cell Longev. 2021 ;2021 5147069

Sesamin Protects against and Ameliorates Rat Intestinal Ischemia/Reperfusion Injury with Involvement of Activating Nrf2/HO-1/NQO1 Signaling Pathway.

Yilin Wang, Jin Wen, Marwan Almoiliqy, Yaojia Wang, Zhihao Liu, Xiaobo Yang, Xiaolong Lu, Qiang Meng, Jinyong Peng, Yuan Lin, Pengyuan Sun.

Intestinal ischemia-reperfusion (I/R) may induce cell/tissue injuries, leading to multiple organ failure. Based on our preexperiments, we proposed that sesamin could protect against and ameliorate intestinal I/R injuries and related disorders with involvement of activating Nrf2 signaling pathway. This proposal was evaluated using SD intestinal I/R injury rats in vivo and hypoxia/reoxygenation- (H/R-) injured rat small intestinal crypt epithelial cell line (IEC-6 cells) in vitro. Sesamin significantly alleviated I/R-induced intestinal histopathological injuries and significantly reduced serum biochemical indicators ALT and AST, alleviating I/R-induced intestinal injury in rats. Sesamin also significantly reversed I/R-increased TNF-α, IL-6, IL-1β, and MPO activity in serum and MDA in tissues and I/R-decreased GSH in tissues and SOD in both tissues and IEC-6 cells, indicating its anti-inflammatory and antioxidative stress effects. Further, sesamin significantly decreased TUNEL-positive cells, downregulated the increased Bax and caspase-3 protein expression, upregulated the decreased protein expression of Bcl-2 in I/R-injured intestinal tissues, and significantly reversed H/R-reduced IEC-6 cell viability as well as reduced the number of apoptotic cells among H/R-injured IEC-6 cell, showing antiapoptotic effects. Activation of Nrf2 is known to ameliorate tissue/cell injuries. Consistent with sesamin-induced ameliorations of both intestinal I/R injuries and H/R injuries, transfection of Nrf2 cDNA significantly upregulated the expression of Nrf2, HO-1, and NQO1, respectively. On the contrary, either Nrf2 inhibitor (ML385) or Nrf2 siRNA transfection significantly decreased the expression of these proteins. Our results suggest that activation of the Nrf2/HO-1/NQO1 signaling pathway is involved in sesamin-induced anti-inflammatory, antioxidative, and antiapoptotic effects in protection against and amelioration of intestinal I/R injuries.

DOI: https://doi.org/10.1155/2021/5147069
J Leukoc Biol. 2021 Oct 12.

Polymorphonuclear myeloid-derived suppressor cells link inflammation and damage response after trauma.

Xinyao Li, Jingping Liu, Zhe Xing, Jian Tang, Hengbiao Sun, Xiaogang Zhang, Shuaijun Lv, Ziyang Chen, Mengyu Shi, Meiqi Chen, Shaowen Zuo, Xiaoming Lyu, Yumei He.

  Elimination of the posttraumatic inflammatory response and recovery of homeostasis are crucial for the positive prognosis of trauma patients. Myeloid-derived suppressor cells (MDSCs) are known to play a regulatory role in the posttraumatic immune response in mice, but their induction source and involved potential mechanism are poorly understood. Here, we report that polymorphonuclear MDSCs (PMN-MDSCs) are activated after trauma and are closely associated with the progression of the posttraumatic inflammatory response. In humans, lectin-type oxidized LDL receptor 1 (LOX1) was used to specifically characterize LOX1+ PMN-MDSCs. Trauma patients showed high intracellular reactive oxygen species (ROS) production, as well as activation of LOX1+ PMN-MDSCs. These MDSCs contribute to the anti-inflammatory immune response by regulating the Treg/Th17 and Th2/Th1 balances after trauma, increasing the levels of anti-inflammatory factors, and decreasing the levels of proinflammatory factors. The number of LOX1+ PMN-MDSCs was positively correlated with the positive clinical prognosis of trauma patients with infection. Activation of LOX1+ PMN-MDSCs is mediated by NF-κB signal, and TGF-β1 may be as an important inducer for LOX1+ PMN-MDSCs in the posttraumatic cytokine environment. In a pseudofracture trauma mouse model, we also observed the activation of PMN-MDSCs, accompanying high levels of intracellular ROS production, NF-κB phosphorylation, and changes in the inflammatory environment, in particularly by regulating the Treg/Th17 and Th2/Th1 balance. And more significantly, posttraumatic inflammation was alleviated in mice after transferring trauma-derived PMN-MDSCs, but aggravated after injecting with Gr1 agonistic antibody. These findings provide evidence for the specific role of PMN-MDSCs in the regulation of posttraumatic inflammation.

Keywords:  inflammation; lectin-type oxidized LDL receptor 1; polymorphonuclear myeloid-derived suppressor cells; regulation; trauma

DOI:  https://doi.org/10.1002/JLB.3MA0821-029R
Cell Calcium. 2021 Oct 05. pii: S0143-4160(21)00137-8. [Epub ahead of print]100 102483

Activation of transient receptor potential vanilloid 4 exacerbates myocardial ischemia-reperfusion injury via JNK-CaMKII phosphorylation pathway in isolated mice hearts.

Shaoshao Zhang, Kai Lu, Shuaitao Yang, Yuwei Wu, Jie Liao, Yang Lu, Qiongfeng Wu, Ning Zhao, Qian Dong, Lei Chen, Yimei Du.

  Previous studies, including our own, have demonstrated that transient receptor potential vanilloid 4 (TRPV4) is involved in myocardial ischemia-reperfusion (IR) injury, yet its underlying molecular mechanism remains unclear. In this study, we isolated mice hearts for a Langendorff perfusion test and used HL-1 myocytes for in vitro assessments. We first confirmed that TRPV4 agonist (GSK101) enhanced myocardial IR injury, as demonstrated by the reduced recovery of cardiac function, larger myocardial infarct size, and more apoptotic cells. We also found that GSK101 could further increase the phosphorylation of JNK and CaMKII in isolated hearts during IR. Notably, GSK101 dose-dependently evoked the phosphorylation of JNK and CaMKII in isolated normal hearts. All above GSK101-induced effects could be significantly blocked by the pharmacological inhibition or genetic ablation of TRPV4. More importantly, JNK inhibition (with SP600125) or CaMKII inhibition (with KN93 or in transgenic AC3-I mice) could prevent GSK101-induced myocardial injury during IR. In HL-1 myocytes, GSK101 triggered Ca2+ influx and evoked the phosphorylation of JNK and CaMKII but these effects were abolished by removing extracellular Ca2+ or in the presence of a TRPV4 antagonist. Finally, we showed that in HL-1 myocytes and isolated hearts during IR, JNK inhibition significantly inhibited the phosphorylation of CaMKII induced by GSK101 but CaMKII inhibition had no effect on JNK activation induced by GSK101. Our data suggest that TRPV4 activation exacerbates myocardial IR injury via the JNK-CaMKII phosphorylation pathway.

Keywords:  CaMKII; Calcium; Ischemia/reperfusion injury; JNK; Transient receptor potential vanilloid 4

DOI:  https://doi.org/10.1016/j.ceca.2021.102483
J Am Coll Emerg Physicians Open. 2021 Oct;2(5): e12536

A simple improvised prehospital method to warm intravenous fluid.

John W Lyng, Michael C Perlmutter, Michaela A West.

   Study Objective: Use of warmed intravenous fluid by emergency medical services (EMS) for prehospital injured patients is recommended to avoid iatrogenic hypothermia. We hypothesized that an improvised heating method would significantly increase the temperature of an intravenous fluid bag in a simulated prehospital environment.
Methods: The change from baseline in the temperature of a 1-L intravenous fluid bag positioned above the vehicle windshield defroster vent was measured for 30 minutes using a thermocouple probe. Temperature changes were compared with a control fluid bag positioned on the vehicle console armrest. A total of 10 independent experiments were performed.
Results: The defroster vent method increased intravenous fluid bag temperature from a mean starting temperature of 19.4°C (95% confidence interval [CI], 17.4°C-21.4°C) to a mean end temperature of 32.6°C (95% CI, 30.6°C-34.6°C) after 30 minutes. The temperature of a control intravenous fluid bag (mean starting temperature of 20.1°C; 95% CI, 19.0°C-21.2°C) exposed to a warmed (mean 33.2°C) passenger compartment changed little during the same time period (mean end temperature of 22.3°C; 95% CI, 19.4°C-25.2°C).
Conclusions: Convective warming of an intravenous fluid bag using the dashboard defroster vent significantly raised the fluid temperature. Such a method should be readily available to EMS or first responders.

Keywords:  austere environments; emergency medical services; hypothermia; prehospital; resuscitation; trauma

DOI:  https://doi.org/10.1002/emp2.12536
World Neurosurg. 2021 Oct 08. pii: S1878-8750(21)01496-0. [Epub ahead of print]

Phosphoinositide-3-kinase/Akt-endothelial nitric oxide synthase signaling pathway mediates the neuroprotective effect of sevoflurane postconditioning in a rat model of hemorrhagic shock and resuscitation.

Muchun Zhang, Chunxia Huang, Li Zhang, Li Huang, Xianwen Hu.

PURPOSE: Extensive reports have demonstrated the neuroprotection of sevoflurane postconditioning under the background of focal and global cerebral ischemia/reperfusion, the underlying mechanisms are not completely elucidated. This study was to investigate if this effect is related to eNOS and mediated by phosphoinositide-3-kinase pathway in a rat model of hemorrhagic shock and resuscitation.
METHODS: Adult male Sprague-Dawley rats were subjected to hemorrhagic shock for 60min and then resuscitation for 30min in exprimental groups. Sevoflurane postconditioning was performed at the beginning of resuscitation till the completion. At 24 hours after resuscitation, the infarct volume of brain was evaluated by TTC staining. The neuronal morphologic changes and apoptosis were determined by H&E staining and immunohistochemistry analysis, respectively. The activity of p-Akt and eNOS were evaluated by Western Blot analysis.
RESULTS: The brain injuries such as the cerebral infarct volume and pathological neuronal changes as well as cell apoptosis were observed in the hippocampus after HSR. Postconditioning with 2.4% sevoflurane significantly attenuated brain injuries. Wortmannin prevented the improvements of neuronal characteristics elicited by sevoflurane postconditioning, as well as the hyperactivity of eNOS and p-Akt.
CONCLUSION: Sevoflurane postconditioning could attenuate brain injury induced by hemorrhagic shock and resuscitation, and this neuroprotective effect may be partly by upregulation of eNOS through PI3K/Akt signaling pathway.

DOI: https://doi.org/10.1016/j.wneu.2021.09.143
Blood Rev. 2021 Oct 02. pii: S0268-960X(21)00097-7. [Epub ahead of print] 100891

The recipe for TACO: A narrative review on the pathophysiology and potential mitigation strategies of transfusion-associated circulatory overload.

Esther B Bulle, Robert B Klanderman, Jacob Pendergrast, Christine Cserti-Gazdewich, Jeannie Callum, Alexander P J Vlaar.

  Transfusion associated circulatory overload (TACO) is one of the leading causes of transfusion related morbidity and mortality. TACO is the result of hydrostatic pulmonary edema following transfusion. However, up to 50% of all TACO cases appear after transfusion of a single unit, suggesting other factors, aside from volume, play a role in its pathophysiology. TACO follows a two-hit model, in which the first hit is an existing disease or comorbidity that renders patients volume incompliant, and the second hit is the transfusion. First hit factors include, amongst others, cardiac and renal failure. Blood product factors, setting TACO apart from crystalloid overload, include colloid osmotic pressure effects, viscosity, pro-inflammatory mediators and storage lesion byproducts. Differing hemodynamic changes, glycocalyx injury, endothelial damage and inflammatory reactions can all contribute to developing TACO. This narrative review explores pathophysiological mechanisms for TACO, discusses related therapeutic and preventative measures, and identifies areas of interest for future research.

Keywords:  Cardiac overload; Hydrostatic pulmonary edema; Transfusion; Volume overload

DOI:  https://doi.org/10.1016/j.blre.2021.100891