Traumatic Hemorrhagic Shock Research Articles

Effect on Syndecan-1 and Hyaluronan Levels Depending on Multiple Organ Failure, Coagulopathy and Survival: An Observational Study in Major Trauma Patients

Background: Major trauma, as well as traumatic hemorrhagic shock go along with early damage to the endothelial glycocalyx (EG). Shed glycocalyx constituents can activate the innate immune system and aggravate secondary injury. Subsequently, we investigated the relationship between glycocalyx shedding and the occurrence of coagulopathy, multiple organ failure (MOF) and outcome in our cohort after severe trauma. Methods: We included multiple trauma patients, as defined by Injury Severity Score (ISS). Polytraumatized patients must have arrived in our level 1 trauma center within 60 min after trauma. Retrospectively, patients were assigned to predefined clinical conditions, based on injury severity (ISS ≥ 16 points), multiple organ failure (MOF score ≥ 6 points), need for massive transfusion (≥10 RBC units/first 24 h), coagulopathy (prothrombin time < 70% at 0 h) and survival (90-day survival). Syndecan-1 (Sdc-1) and hyaluronan (HA) plasma concentrations were evaluated immediately (0 h), 6 h and 12 h after trauma. Results: 49 patients (mean ISS 35.7 ± 12.1 SD, mean age 45.78 ± 15.6 SD) were included in this study. A total of 37 patients (75.5%) survived, while 12 patients died within the observation period of 90 days after trauma (24.5%). A total of 77% of all patients suffered multiple organ failure (MOF score ≥ 6, n = 30). Initial prothrombin time at 0 h was <70% in 31 patients. Plasma concentrations of circulating both glycocalyx constituents showed a significant increase over the first 12 h after trauma (p = 0.001; p = 0.008). Patients with multiple organ failure showed significantly increased hyaluronan concentrations at all three time points (p = 0.007/0.006/<0.001), and the syndecan-1 levels were significantly elevated 12 h after trauma in the MOF group (p = 0.01). Patients with coagulopathy on admission exhibited significantly higher hyaluronan levels at 12 h (p = 0.042). Non-survivors showed significantly increased syndecan-1 levels at 12 h after trauma (p = 0.024). Conclusions: Glycocalyx shedding occurs immediately after major trauma. Coagulopathy is associated with significantly increased plasma hyaluronan. Further, significant changes in plasma concentrations within the first 12 h help to identify subgroups at risk for developing MOF and death.

Analysis of the Emergency Rescue Nursing Intervention Effect and Rescue Success Rate for Patients with Traumatic Hemorrhagic Shock

Objective: To analyze the value of emergency rescue nursing intervention in the care of patients with traumatic hemorrhagic shock and its impact on the success rate of rescue efforts. Methods: A total of 80 patients with traumatic hemorrhagic shock were selected as samples, with the timeframe from July 2022 to July 2023. The patients were randomly divided into two groups using a random number table method. Group A received emergency rescue nursing, while Group B received routine nursing care. The success rate of rescue, rescue indicators, complication rates, and family satisfaction with nursing care were compared between the two groups. Results: The rescue success rate in Group A was higher than in Group B (P < 0.05); the total blood loss in Group A was less, and the rescue time, full transportation time, and hospitalization time were shorter than in Group B (P < 0.05); the complication rate of patients with traumatic hemorrhagic shock in Group A was lower than in Group B (P < 0.05); the family satisfaction with emergency nursing care in Group A was higher than in Group B (P < 0.05). Conclusion: Emergency rescue interventions for patients with traumatic hemorrhagic shock can reduce blood loss, shorten rescue times, and improve the success rate of shock rescue, providing a safe and effective approach.

Testing Neuroprotective Strategies in Prolonged Field Care Model of Traumatic Brain Injury and Hemorrhagic Shock.

Prolonged Field Care (PFC) is a military adaptation of Tactical Combat Casualty Care providing extended pre-hospital management during delayed extrication. Effects of addition of Valproic Acid (VPA) to Fresh Frozen Plasma (FFP) in a PFC model of hemorrhagic shock and traumatic brain injury (TBI) are not known. We hypothesized that VPA is associated with decreased neurological impairment, and its protective changes are detected at the transcriptomic level. Swine underwent TBI and 40%-blood volume hemorrhage. After 2-hours of shock, they were randomized to: 1)normal saline (NS), 2)NS+250 ml FFP (NS+FFP), or 3)NS+FFP+150 mg/kgVPA(NS+FFP+VPA). At 72-hours, they were transfused packed red blood cells before being euthanized. Intraoperative variables and neurological outcomes were compared. Brain lesion size was measured, and gene expression profiles were analyzed using RNA-sequencing. Pathway and network analyses were performed on differentially expressed genes. Real-time PCR was performed to validate key genes. NS+FFP and NS+FFP+VPA required significantly less crystalloid resuscitation(974 ml-NS+FFP; 1461ml-NS+FFP+VPA vs. 4540 ml-NS, p<0.001), had smaller brain lesion size(2477mm3-NS+FFP; 3018.0mm3-NS+FFP+VPA vs. 4517.0mm3-NS, p<0.01), and less functional neurologic impairment compared to NS. Per pathway analysis of differentially expressed genes, VPA was associated with enrichment of numerous metabolic changes in injured brains, which were not observed with FFP. Network analysis showed enrichment of various gene networks. MT-ATP8 gene was downregulated in VPA-treated animals. The addition of FFP to the resuscitation protocol resulted in a significant reduction in crystalloid requirements. Both, the FFP and FFP+VPA groups showed improved neurological recovery compared to NS alone and had distinctive transcriptomic profiles in injured brains at 72-hours. MT-ATP8, involved in worsening ischemia following brain injury, was down-regulated in VPA-treated animals.

Use of resuscitative endovascular balloon occlusion of the aorta (REBOA) in a multidisciplinary approach for management of traumatic haemorrhagic shock: 10-year retrospective experience from a French level 1 trauma centre

BackgroundThe present study investigated an institutional multidisciplinary strategy for managing traumatic haemorrhagic shock by integrating the placement of REBOA (resuscitative endovascular balloon occlusion of the aorta) by anaesthesiologist-intensivists. MethodsAll severe trauma patients who received percutaneous REBOA placement between January 2013 and December 2022 in our level 1 trauma centre were retrospectively analysed. The data collected included the clinical context, indications and location of REBOA, durations of aortic occlusion (AO), choice of haemostatic procedures and surgical teams, and specific complications. ResultsIn total, 38 trauma patients were included in the present study (mean age = 41 years [standard deviation = 21 years], 31 [82 %] were male, and median injury severity score was 62.5 [inter-quartile range (IQR) = 45–75]). REBOA was always placed by anaesthesiologist-intensivists, who comprised 68 % of the senior physicians (13/19) in our trauma team over the period. Twenty-eight AOs (74 %) were performed in zone 1 and 10 (26 %) in zone 3. Twelve patients (32 %) received REBOA upon circulatory arrest. Routes following REBOA placement comprised: computed tomography scan = 47 %, operating room = 34 %, angiography = 3 %, emergency room thoracotomy = 5 %, and prematurely died = 11 %. Duration of AO was 38 min (IQR = 32–44 min) in zone 1 and 78 min (IQR = 48–112 min) in zone 3. Mortality rate was 66 % (95 % CI 51–81 %) and higher in cases of AO in zone 1 (79 % versus 30 %, p = 0.018) or concomitant with circulatory arrest (92 % versus 54 %, p = 0.047). No ischemic limb needed an intervention and three endothelial injuries required delayed endovascular stenting. ConclusionsPercutaneous REBOA placement by anaesthesiologist-intensivists included in the multidisciplinary management of traumatic haemorrhagic shock was associated with acceptable time of AO and local complications similar to those observed in other series.

The mitochondrial division inhibitor Mdivi-1 protected organ function and extended the treatment window in rats with uncontrolled haemorrhagic shock.

To elucidate whether the application of the mitochondrial division inhibitor Mdivi-1 can protect organ function and prolong the treatment window for traumatic hemorrhagic shock. Before definitive haemostasis treatment, Mdivi-1 (0.25 mg/kg, 0.5 mg/kg and 1 mg/kg) was administered to uncontrolled haemorrhagic shock (UHS) model rats. Lactate Ringer's solution plus hydroxyethyl starch (130/0.4) was used as a control. The effects of Mdivi-1 on blood loss, fluid demand, survival time, vital organ function, myocardial mitochondrial structure, and mitochondrial function of the heart, liver, kidney and intestine, and oxidative stress at 1 hour after hypotensive resuscitation (50-60 mmHg) were investigated. In addition, we investigated the effect of varying doses of Mdivi-1 on the maintenance time of hypotensive resuscitation without definitive haemostasis and the beneficial effect of Mdivi-1 after prolonging the duration of hypotensive resuscitation to 2 hours. Compared to conventional resuscitative fluid, Mdivi-1 significantly reduced blood loss and fluid demand, improved important organ functions during hypotensive resuscitation, improved animal survival and reduced the incidence of early death. Mdivi-1 significantly alleviated oxidative stress injury, reduced mitochondrial damage and restored myocardial mitochondrial structure and mitochondrial function of the heart, liver, kidney and intestine. In addition, Mdivi-1 increased the maintenance time of hypotensive resuscitation and improved rat survival after the duration of hypotensive resuscitation was prolonged to 2 h. Mdivi-1 significantly prolonged the treatment window for traumatic hemorrhagic shock to 2 hours in UHS model rats. The underlying mechanism may be that Mdivi-1 inhibits excessive mitochondrial fission and oxidative stress and improves the structure and function of mitochondria.

Incidence and risk factors for acute kidney injury after traumatic hemorrhagic shock: A 10-year retrospective cohort study.

Acute kidney injury (AKI) is a common complication of traumatic hemorrhagic shock. Therisk factors for AKI aftertraumatic hemorrhagic shockremain unclear. The aim of this study was to investigate the risk factors for AKI after traumatic hemorrhagic shock. This was a ten-year retrospective cohort study of patients who experiencedtraumatic hemorrhagic shock between January 2013 and April 2023. Patient characteristics and clinical data were recorded for 417 patients. The outcome was the occurrence of AKI, defined as a serum creatinine increase of ≥ 0.3mg/dL (≥ 26.5μmol/L) within 48h, or an increase to 1.5 times the baseline, or a urine volume of <0.5mL/(kg h.). Risk factors for AKI were tested by logistic regressionmodels. The incidence of AKI after traumatic hemorrhagic shockwas 29.3% (122/417 patients). Multivariable analysis revealed that the independent risk factors for AKIincluded age (OR, 1.048; 95% CI, 1.022-1.074; p < 0.001), B-type natriuretic peptide (OR, 1.002; 95% CI, 1.000-1.004; p = 0.041), sepsis (OR, 4.536; 95% CI, 1.651-12.462; p = 0.030) and acute myocardial injury (OR, 2.745; 95% CI, 1.027-7.342; p = 0.044). Road traffic accidents (OR, 0.202; 95% CI, 0.076-0.541; p = 0.001), mean arterial pressure (OR, 0.972; 95% CI, 0.950-0.995; p = 0.017), and base excess (OR, 0.842; 95% CI, 0.764-0.929; p = 0.001) were negatively correlated with AKI. The area under the receiver operating characteristic (ROC)curvefor prediction by thismodel was 0.85(95% CI, 0.81-0.90). The incidence of AKI aftertraumatic hemorrhagic shockwas 29.3%in our series. Indicators of bloodperfusion, sepsis and acute myocardial injury may be independent risk factors for AKI aftertraumatic hemorrhagic shock. Early detection and effective intervention on these risk factors could reduce the occurrence of AKI and improve outcomes.

β-Adrenoceptor Agonists Attenuate Thrombin-Induced Impairment of Human Lung Endothelial Cell Barrier Function and Protect the Lung Vascular Barrier during Resuscitation from Hemorrhagic Shock.

β-adrenoceptor (β-AR) agonists are known to antagonize thrombin-induced impairment (TII) of bovine and ovine lung endothelial barrier function. The effects of adrenoceptor agonists and other vasoactive agents on human lung microvascular endothelial cell (HULEC-5a) barrier function upon thrombin exposure have not been studied. Furthermore, it is unknown whether the in vitro effects of adrenoceptor agonists translate to lung protective effects in vivo. We observed that epinephrine, norepinephrine, and phenylephrine enhanced normal and prevented TII of HULEC-5a barrier function. Arginine vasopressin and angiotensin II were ineffective. α1B-, α2A/B-, and β1/2-ARs were detectable in HULEC-5a by RT-PCR. Propranolol but not doxazosin blocked the effects of all adrenoceptor agonists. Phenylephrine stimulated β2-AR-mediated Gαs activation with 13-fold lower potency than epinephrine. The EC50 to inhibit TII of HULEC-5a barrier function was 1.8 ± 1.9 nM for epinephrine and >100 nM for phenylephrine. After hemorrhagic shock and fluid resuscitation in rats, Evans blue extravasation into the lung increased threefold (p < 0.01 vs. sham). Single low-dose (1.8 μg/kg) epinephrine administration at the beginning of resuscitation had no effects on blood pressure and reduced Evans blue extravasation by 60% (p < 0.05 vs. vehicle). Our findings confirm the effects of β-adrenoceptor agonists in HULEC-5a and suggest that low-dose β-adrenoceptor agonist treatment protects lung vascular barrier function after traumatic hemorrhagic shock.

Efficacy and safety of novel freeze-dried plasma products in a porcine combat casualty model.

Hemorrhagic shock is well documented as a leading cause of preventable fatalities among military casualties. During military operations plasma can be transfused while waiting for whole blood. This study was conducted to assess the safety and efficacy of two new freeze-dried plasma formulations in a porcine model of traumatic hemorrhagic shock. In the face of species-specific transfusion, transfusible blood products were derived from porcine sources. The efficacy of three lyophilized plasma (LP) formulations was evaluated: lyophilized plasma (LP), concentrated lyophilized plasma (CLP), and platelet-rich concentrated lyophilized plasma (PCLP). Pigs were subjected to multi-trauma and hemorrhagic shock. Ninety minutes post-shock induction, the animals were treated with one of the three lyophilized products. Monitoring included systolic blood pressure and cardiac output. Point-of-care and laboratory diagnostic tests were used to assess renal function, real-time hemostasis (ROTEM), and coagulation. Histological examinations of kidney, lung, and muscle tissues were conducted 4 h after shock induction. CLP and PCLP significantly improved systolic blood pressure and cardiac output and positively influenced base excess, creatinine, various ROTEM, and coagulation markers compared with standard LP without histologic modification. No adverse effect was associated with the transfusion of any of the plasma products throughout the experimental procedures. Both CLP and PCLP exhibit promising therapeutic potential for managing hemorrhagic shock in scenario where whole blood supplies are limited. However, the distinct physiological and coagulation characteristics of the swine model necessitate further investigation using humanized preclinical models to fully understand their clinical applicability and constraints.

MKK3 depletion attenuates intestinal injury after traumatic hemorrhagic shock by restoring mitochondrial function.

Traumatic hemorrhagic shock (THS) is a complex pathophysiological process resulting in multiple organ failure. Intestinal barrier dysfunction is one of the mechanisms implicated in multiple organ failure. The present study aimed to explore the regulatory role of mitogen-activated protein kinase kinase 3 (MKK3) in THS-induced intestinal injury and to elucidate its potential mechanism. Rats were subjected to trauma and hemorrhage to establish a THS animal model. MKK3-targeted lentiviral vectors were injected via the tail vein 72h before modeling. Twelve hours post-modeling, the mean arterial pressure (MAP) and heart rate (HR) were monitored, and histological injury to the intestine was assessed via H&E staining and transmission electron microscopy. Mitochondrial function and mitochondrial reactive oxygen species (ROS) were evaluated. IEC-6 cells were exposed to hypoxia to mimic intestinal injury following THS in vitro. MKK3 deficiency alleviated intestinal injury and restored mitochondrial function in intestinal tissues from THS-induced rats and hypoxia-treated IEC-6 cells. In addition, MKK3 deficiency promoted Sirt1/PGC-1α-mediated mitochondrial biogenesis and restricted Pink1/Parkin-mediated mitophagy in the injured intestine and IEC-6 cells. Furthermore, the protective effect of MKK3 knockdown against hypoxia-induced mitochondrial damage was strengthened upon simultaneous LC3B/Pink1/Parkin knockdown or weakened upon simultaneous Sirt1 knockdown. MKK3 deficiency protected against intestinal injury induced by THS by promoting mitochondrial biogenesis and restricting excessive mitophagy.

A rat model of multicompartmental traumatic injury and hemorrhagic shock induces bone marrow dysfunction and profound anemia.

Severe trauma is associated with systemic inflammation and organ dysfunction. Preclinical rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human trauma. The aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic injury. Male Sprague-Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock (LCHS), multicompartmental polytrauma (PT) (unilateral lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofracture), or naïve controls. Weight, plasma toll-like receptor 4 (TLR4), hemoglobin, spleen to body weight ratio, bone marrow (BM) erythroid progenitor (CFU-GEMM, BFU-E, and CFU-E) growth, plasma granulocyte colony-stimulating factor (G-CSF) and right lung histologic injury were assessed on day 7, with significance defined as p values <0.05 (*). Polytrauma resulted in markedly more profound inhibition of weight gain compared to LCHS (p = 0.0002) along with elevated plasma TLR4 (p < 0.0001), lower hemoglobin (p < 0.0001), and enlarged spleen to body weight ratios (p = 0.004). Both LCHS and PT demonstrated suppression of CFU-E and BFU-E growth compared to naïve (p < 0.03, p < 0.01). Plasma G-CSF was elevated in PT compared to both naïve and LCHS (p < 0.0001, p = 0.02). LCHS and PT demonstrated significant histologic right lung injury with poor alveolar wall integrity and interstitial edema. Multicompartmental injury as described here establishes a reproducible model of multicompartmental injury with worsened anemia, splenic tissue enlargement, weight loss, and increased inflammatory activity compared to a less severe model. This may serve as a more effective model to recreate profound traumatic injury to replicate the human inflammatory response postinjury.

Enteral Protease Inhibition Preserves Aortic Ultrastructure and Mechanics in Experimental Trauma/Hemorrhagic Shock

Introduction: Vascular compliance of large arteries is often overlooked in acute trauma/hemorrhagic shock (T/HS), as standard interventions, such as vasopressors, typically target systemic vascular resistance (SVR) regulated by small arterioles. However, patients may become refractory to vasopressors, and efforts to raise SVR may not restore mean arterial blood pressure (MAP), which is crucial for organ perfusion. We have previously reported compromised vascular compliance after T/HS in vivo with increased pulse wave velocity and ex vivo with diminished circumferential distensibility, that were both partially mitigated by enteral serine protease inhibition. To further elucidate the mechanisms behind these adverse changes, our aim was to directly assess the material stiffness, extracellular matrix (ECM) morphology, and matrix metalloproteinase (MMP) activity within the aortic wall tissue after T/HS, as well as to evaluate the effectiveness of enteral protease inhibition in this context.Methods: Anesthetized Wistar rats (350 - 400g) underwent laparotomy (trauma) and exsanguination to maintain a MAP of 35-40 mmHg for 90 minutes (shock). Animals were randomly assigned to receive either enteral gabexate mesilate protease inhibitor treatment (GM-treated) or vehicle-only (Untreated) via an orally-inserted catheter; investigators were blinded to the treatment assignation. At the conclusion of the shock period, animals were resuscitated with intravenous Lactated Ringer’s solution (LR) for two hours to achieve and maintain a MAP of at least 60 mmHg. A sham control group was also included for comparison. In all groups, the thoracic aorta was bisected, with one half sectioned for atomic force microscopy and histology and the other half homogenized for gelatin zymography. Liquid-phase force mapping was conducted on random areas (1600 μm2) of the medial layer in triplicate to determine the average Young’s modulus of the tissue. Collagen fibers were stained with picrosirius red, and elastin fibers were stained with Verhoeff Van Gieson. Results: After being subjected to T/HS and LR reperfusion, the aortic media of the Untreated group had a significantly higher average Young’s modulus than that of healthy sham vessels (862.7 kPa vs. 556.5 kPa, p &lt; 0.05). The GM-treated group, however, better preserved its material elasticity (~650 kPa). These stiffness values negatively correlate with corresponding animals’ final MAP values measured at the end of the reperfusion period (r2 = 0.5031), supporting an association between vascular compliance and hemodynamic stability. The area of collagen within the tunica media was found to be significantly decreased in the Untreated compared to the sham group (4.93% vs. 10.26%, p &lt; 0.05), but GM treatment was able to prevent collagen degradation (8.48%). Disruptions in elastin fibers were also observed at a higher frequency in the Untreated T/HS aorta compared to sham controls (3.3 vs. 1.7, p &lt; 0.05) or GM-treated aortas (3.3 vs. 1.6, p &lt; 0.05). Gelatin zymography revealed that enteral GM treatment also significantly attenuated elevated plasma MMP-9 (0.85 vs. 1.97 A.U., p &lt; 0.01) and tissue MMP-2 activity (0.86 vs. 1.80 A.U., p &lt; 0.05) seen following T/HS. Conclusions: Fluid-resuscitated traumatic hemorrhagic shock resulted in ultrastructural and biomechanical alterations in the aorta, indicating a loss in compliance. Enteral gabexate mesilate treatment effectively mitigated these pathological changes to the vasculature, suggesting the potential involvement of serine proteases in aortic ECM remodeling and large artery dysfunction in T/HS. Interventions against central artery impairment may be a promising strategy for improving blood pressure and survival in circulatory shock. Department of Defense Award W81XWH-17-2-0047. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of different types of Ringer’s solution on patients with traumatic haemorrhagic shock: a prospective cohort study

ObjectiveTo compare the fluid resuscitation effect of sodium acetate Ringer’s solution and sodium bicarbonate Ringer’s solution on patients with traumatic haemorrhagic shock.MethodWe conducted a prospective cohort study in our emergency department on a total of 71 patients with traumatic haemorrhagic shock admitted between 1 December 2020 and 28 February 2022. Based on the time of admission, patients were randomly divided into a sodium bicarbonate Ringer’s solution group and sodium acetate Ringer’s solution group, and a limited rehydration resuscitation strategy was adopted in both groups. General data were collected separately, and the patients’ vital signs (body temperature, respiration, blood pressure and mean arterial pressure (MAP)), blood gas indices (pH, calculated bicarbonate (cHCO3−), partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (pCO2) and clearance of lactate (CLac)), shock indices, peripheral platelet counts, prothrombin times and plasma fibrinogen levels were measured and compared before and 1 h after resuscitation.ResultsThe post-resuscitation heart rate of the sodium bicarbonate Ringer’s solution group was significantly lower than that of the sodium acetate Ringer’s solution group (p < 0.05), and the MAP was also significantly lower (p < 0.05). The patients in the sodium bicarbonate Ringer’s solution group had significantly higher pH, cHCO3− and PaO2 values and lower pCO2 and CLac values (p < 0.05) than those in the sodium acetate Ringer’s solution group, and the post-resuscitation peripheral platelet counts and fibrinogen levels were significantly higher, with shorter plasma prothrombin times and smaller shock indices (p < 0.001).ConclusionSodium bicarbonate Ringer’s solution is beneficial for maintaining MAP at a low level after resuscitation. The use of sodium bicarbonate Ringer’s solution in limited fluid resuscitation has positive results and is of high clinical value.

VX-765 Alleviates Circadian Rhythm Disorder in a Rodent Model of Traumatic Brain Injury Plus Hemorrhagic Shock and Resuscitation.

Severe traumatic brain injury (TBI) can result in persistent complications, including circadian rhythm disorder, that substantially affect not only the injured people, but also the mood and social interactions with the family and the community. Pyroptosis in GFAP-positive astrocytes plays a vital role in inflammatory changes post-TBI. We determined whether VX-765, a low molecular weight caspase-1 inhibitor, has potential therapeutic value against astrocytic inflammation and pyroptosis in a rodent model of TBI plus hemorrhagic shock and resuscitation (HSR). A weight-drop plus bleeding and refusion model was used to establish traumatic exposure in rats. VX-765 (50mg/kg) was injected via the femoral vein after resuscitation. Wheel-running activity was assessed, brain magnetic resonance images were evaluated, the expression of pyroptosis-associated molecules including cleaved caspase-1, gasdermin D (GSDMD), and interleukin-18 (IL-18) in astrocytes in the region of anterior hypothalamus, were explored 30days post-trauma. VX-765-treated rats had significant improvement in circadian rhythm disorder, decreased mean diffusivity (MD) and mean kurtosis (MK), increased fractional anisotropy (FA), an elevated number and branches of astrocytes, and lower cleaved caspase-1, GSDMD, and IL-18 expression in astrocytes than TBI + HSR-treated rats. These results demonstrated that inhibition of pyroptosis-associated astrocytic activations in the anterior hypothalamus using VX-765 may ameliorate circadian rhythm disorder after trauma. In conclusion, we suggest that interventions targeting caspase-1-induced astrocytic pyroptosis by VX-765 are promising strategies to alleviate circadian rhythm disorder post-TBI.

Retracted: Correlation between Coagulation Fibrinolysis Function and Outcomes during Hospitalization in Patients with Severe Traumatic Hemorrhagic Shock.

[This retracts the article DOI: 10.1155/2022/3775868.].

EFFECT OF MIR-21-3P ON INTESTINAL INJURY IN RATS WITH TRAUMATIC HEMORRHAGIC SHOCK RESUSCITATED WITH THE SODIUM BICARBONATE RINGER'S SOLUTION.

Background : This study aims to determine the impact and mechanism of miR-21-3p on intestinal injury and intestinal glycocalyx during fluid resuscitation in traumatic hemorrhagic shock (THS), and the different impacts of sodium lactate Ringer's solution (LRS) and sodium bicarbonate Ringer's solution (BRS) for resuscitation on intestinal damage. Methods : A rat model of THS was induced by hemorrhage from the left femur fracture. The pathological changes of intestinal tissues and glycocalyx structure were observed by hematoxylin-eosin staining and transmission electron microscope. MiR-21-3p expression in intestinal tissues was detected by real-time quantitative polymerase chain reaction. The expression of glycocalyx-, cell junction-, and PI3K/Akt/NF-κB signaling pathway-related proteins was analyzed by western blot. Results : MiR-21-3p expression was increased in THS rats, which was suppressed by resuscitation with BRS. BRS or LRS aggravated the intestinal injury and damaged intestinal glycocalyx in THS rats. The expression of SDC-1, HPA, β-catenin, MMP2, and MMP9 was upregulated, the expression of E-cad was downregulated, and the PI3K/Akt/NF-κB signaling pathway was activated in THS rats, which were further aggravated by BRS or LRS. The adverse effect of LRS was more serious than BRS. MiR-21-3p overexpression deteriorated the injury of intestinal tissues and intestinal glycocalyx; increased the expression of SDC-1, HPA, β-catenin, MMP2, and MMP9 while decreasing E-cad expression; and activated the PI3K/Akt/NF-κB signaling pathway in BRS-resuscitated THS rats. Conclusion : MiR-21-3p aggravated intestinal tissue injury and intestinal glycocalyx damage through activating PI3K/Akt/NF-κB signaling pathway in rats with THS resuscitated with BRS.

Atrial natriuretic peptide protects against gut barrier injury through PLC-γ1/ROS feedback loop in rats following traumatic hemorrhagic shock

Introduction The mechanisms underlying the protective effects of atrial natriuretic peptide (ANP) on the gut barrier during traumatic hemorrhagic shock (THS) remain elusive. This study aimed to explore the potential role of ANP in safeguarding against gut barrier dysfunction after THS, focusing on the PLC-γ1/ROS feedback loop. Methods In our THS rat model, we randomly allocated male Sprague-Dawley rats to receive intravenous ANP with or without a concurrent NADPH oxidase/p38 MAPK inhibitor during the shock phase. After 24 h, we assessed circulatory and jejunal ANP, ROS, intestinal tight junction proteins, and apoptosis to evaluate the effects of ANP on the gut barrier and its interplay with intestinal ANP and ROS. Rat small intestinal epithelial cells (IECs) were also treated with ANP and subjected to hypoxia/re-oxygenation injury, with or without PI3K/PLC inhibition, to elucidate the relationship between ANP/ROS signaling and PLC-γ1. Furthermore, we modulated PLC-γ1 expression in these IECs to examine its impact on ROS and ANP production. Results Intravenous ANP administration at 0.025 μg/kg/min during THS significantly increased intestinal ANP and ROS levels at 24 h. ANP treatment enhanced the expression of intestinal tight junction proteins and reduced IEC apoptosis. Inhibition of circulatory ROS diminished intestinal ANP levels, while suppression of circulatory ANP led to a reduction in intestinal ROS. Decreasing PLC-γ1 expression in hypoxia/re-oxygenation-treated IECs resulted in lower ROS and ANP levels, whereas augmenting PLC-γ1 expression did not alter these levels. Additionally, PI3K inhibition markedly decreased PLC-γ1 expression in these cells. Conclusion ANP-induced protection of the intestinal barrier in THS is mediated by an intrinsic PLC-γ1/ROS positive feedback loop. ANP preserves gut barrier integrity and reduces IEC apoptosis through this mechanism. Further studies are warranted to investigate the interaction between IECs and other cellular components within the PLC-γ1/ROS loop.

Effects of restrictive fluid resuscitation on the clinical efficacy of treating traumatic hemorrhagic shock combined with traumatic coagulopathy

This study aims to assess the clinical efficacy of limited fluid resuscitation on traumatic hemorrhagic shock combined with traumatic coagulopathy. A cohort of 120 patients with traumatic hemorrhagic shock complicated with traumatic coagulopathy at admission were divided into two groups based on their emergency fluid resuscitation: the study group (received restrictive fluid resuscitation) and the control group (received conventional fluid resuscitation). Then, the incidence of complications, coagulation parameters, blood gas parameters and electrolyte parameters between the two groups were compared. The incidence of complications in the study group was 6.67%, which was significantly lower than the 20.00% observed in the control group (p &lt; 0.05). Before resuscitation, there was no significant difference in coagulation parameters, blood gas parameters and electrolyte parameters between the two groups (p &gt; 0.05), and in both groups, before and after resuscitation, the coagulation parameters after resuscitation were higher than those before resuscitation, blood gas parameters were lower than those before resuscitation, Mg2+, Cl− and Na+ levels were higher than those before resuscitation, K+ was lower than that before resuscitation, and the difference had statistical significance (p &lt; 0.05). After resuscitation, the coagulation parameters in the study group were significantly lower than those in the control group, the BL (Blood Lactic Acid) and PaCO2 (partial pressure of carbon dioxide in arterial blood) levels in the study group were lower than those in the control group, the BE (base excess) and PaO2 levels were higher than those in the control group, and the differences were statistically significant (p &lt; 0.05). However, after resuscitation, we found no significant difference in electrolyte parameters between both groups (p &gt; 0.05). Restrictive fluid resuscitation was found to significantly enhance coagulation and blood gas function, stabilize water and electrolyte balance and reduce complications in traumatic hemorrhagic shock patients complicated with traumatic coagulopathy. These findings hold substantial clinical significance and merit further exploration.

Small-Volume Multifunctional Emergency Resuscitation Fluid Including Colloid Plasma Expander, Artificial Oxygen Carrier, and Coagulation Factors in Traumatic Hemorrhagic Shock When Blood Is Unavailable.

Small-Volume Multifunctional Emergency Resuscitation Fluid Including Colloid Plasma Expander, Artificial Oxygen Carrier, and Coagulation Factors in Traumatic Hemorrhagic Shock When Blood Is Unavailable.

Lactate and base excess (BE) as markers of hypoperfusion and mortality in traumatic hemorrhagic shock in patients undergoing Damage Control: a historical cohort.

hemorrhagic shock is a significant cause of trauma-related deaths in Brazil and worldwide. This study aims to compare BE and lactate values at ICU admission and twenty-four hours after in identifying tissue hypoperfusion and mortality. examines a historical cohort of trauma patients over eitheen years old submittet to damage control resuscitation approch upon hospital admission and were then admitted to the ICU. We collected and analyzed ISS, mechanism and type of trauma, need for renal replacement therapy, massive transfusion. BE, lactate, pH, bicarbonate at ICU admission and twenty-four hours later, and mortality data. The patients were grouped based on their BE values (≥-6 and <-6mmol/L), which were previously identified in the literature as predictors of severity. They were subsequently redivided using the most accurate values found in this sample. In addition to performing multivariate binary logistic regression. The data were compared using several statistical tests due to diversity and according to the indication for each variable. there were significant changes in perfusion upon admission to the Intensive Care Unit. BE is a statistically significant value for predicting mortality, as determined by using values from previous literature and from this study. the results demonstrate the importance of monitoring BE levels in the prediction of ICU mortality. BE proves to be a valuable bedside marker with quick results and wide availability.

Alleviation of Post-sepsis Ischaemia by Drag-Reducing Polymers.

Sepsis, leading to septic shock and multiple organ dysfunction syndrome, is characterised by inflammation, coagulopathy, and microvascular dysfunction, the primary cause of in-hospital mortality. Novel approaches are needed to prevent the consequences of sepsis. We showed that nanomolar concentrations of intravascular blood-soluble drag-reducing polymers (DRPs) significantly improve microvascular perfusion and tissue oxygenation and protect neurons in rat brains after traumatic brain injury and haemorrhagic shock. The aim of this work was to determine whether DRPs-enhanced perfusion could alleviate sepsis-associated microvascular dysregulation in a mouse model of lipopolysaccharide (LPS)-induced sepsis. LPS (Salmonella Thyphosa, 10mg/kg, i.v.) was administered intravenously to induce acute sepsis in C57BL/6 J mice. DRPs (final concentration 5ppm in the blood) or saline was injected i.v. (10 mice/group) 1h after LPS injection to evaluate the efficacy of haemorheological modulation of microvascular dysregulation. In-vivo two-photon laser scanning microscopy was used to monitor cerebral (parietal cortex) and peripheral (ear) microcirculation (i.v. fluorescein isothiocyanate dextran) and tissue oxygen supply (nicotinamide adenine dinucleotide autofluorescence) at a baseline and during 4h after septic shock induction. Differences between groups were determined using a two-way analysis of variance for multiple comparisons with post hoc testing. The statistical significance was set at p<0.05. LPS-induced sepsis led to microvascular dysfunction and tissue hypoxia in the brain and peripheral tissue (ear). DRPs alleviated microthrombosis formation, microvascular dysfunction, and tissue hypoxia in the brain and peripheral tissue compared to the saline control group (p<0.05). Therefore, haemorheological modulation of blood flow by DRPs effectively improves systemic and peripheral circulation, reducing microthrombosis formation, microvascular dysfunction, and tissue hypoxia that can alleviate sepsis, shock, and multiple organ dysfunction syndrome.