Modified Glucose-insulin-potassium Therapy for Hemorrhage-induced Traumatic Cardiac Arrest in Rabbits.

OBJECTIVE: Resuscitation with whole blood is known to be better than that with saline in attaining the return of spontaneous circulation (ROSC) and improving the short-term survival rate for hemorrhage-induced traumatic cardiac arrest (HiTCA). However, the resuscitation with whole blood alone fails to address the pathophysiological abnormalities, including hyperglycemia, hyperkalemia and coagulopathy, after HiTCA. The present study aimed to determine whether the modified glucose-insulin-potassium (GIK) therapy can ameliorate the above-mentioned pathophysiological abnormalities, enhance the ROSC, improve the function of key organs, and reduce the mortality after HiTCA. METHODS: HiTCA was induced in rabbits (n=36) by controlled hemorrhage. Following arrest, the rabbits were randomly divided into three groups (n=12 each): group A (no resuscitation), group B (resuscitation with whole blood), and group C (resuscitation with whole blood plus GIK). The GIK therapy was administered based on the actual concentration of glucose and potassium. The ROSC rate and survival rate were obtained. Hemodynamical and biochemical changes were detected. Thromboelastography (TEG) was used to measure coagulation parameters, and enzyme-linked immunosorbent assay to detect parameters related to inflammation, coagulation and the function of brain. RESULTS: All animals in groups B and C attained ROSC. Two rabbits died 24-48 h after HiTCA in group B, while no rabbits died in group C. The GIK therapy significantly reduced the levels of blood glucose, potassium, and biological markers for inflammatory reaction, and improved the heart, kidney, liver and brain function in group C when compared to group B. Furthermore, the R values of TEG were significantly lower in group C than in group B, and the maximum amplitude of TEG was slightly lower in group B than in group C, with no significant difference found. CONCLUSION: Resuscitation with whole blood and modified GIK therapy combined can ameliorate the pathophysiological disorders, including hyperglycemia, hyperkalemia and coagulopathy, and may improve the function of key organs after HiTCA.

Awake rabbit model of ischemic spinal cord injury with delayed paraplegia: The role of ambient temperature.

BACKGROUND: Paraplegia after spinal cord ischemia is a devastating condition in the clinic. Here, we develop an awake rabbit model of spinal cord ischemia with delayed paraplegia and explore the influence of ambient temperature on the outcomes after injury. METHODS: A total of 47 male rabbits were involved in the present study. Transient spinal cord ischemia was induced by occluding the infrarenal abdominal aorta of awake rabbits at different ambient temperatures. To find the optimal conditions for developing delayed paraplegia, hindlimb motor function after ischemia was evaluated between experiments. RESULTS: The onset and magnitude of ischemic injury varied with the ambient temperature maintained during the peri-ischemia period. More serious spinal cord injury occurred when ischemia was induced at higher temperatures. At 18°C, 25-minute ischemia resulted in 74% of rabbits developing delayed paraplegia. At a temperature of 28°C or higher, most of the animals developed acute paraplegia immediately. While at 13°C, rabbits usually regained normal motor function without paraplegia. CONCLUSION: This awake rabbit model is highly reproducible and will be helpful in future studies of delayed paraplegia after spinal cord ischemia. The ambient temperature must be considered while using this model during investigation of therapeutic interventions.

Features of Coagulo-Fibrinolytic Derangement Due to Bleeding in Nonacclimatized Rabbits Acutely Exposed to High Altitude.

Zhong, Xin, Wenqiong Du, Zhaowen Zong, Renqing Jiang, Yijun Jia, Zhao Ye, and Haoyang Yang. Features of coagulo-fibrinolytic derangement due to bleeding in nonacclimatized rabbits acutely exposed to high altitude. High Alt Med Biol. 24:68-75, 2023. Background: The present study aimed to observe the time course of coagulo-fibrinolytic derangement due to bleeding in rabbits acutely exposed to high altitude (HA). Materials and Methods: Forty-eight rabbits were randomly divided into four groups and were subjected to minor bleeding at low altitude, major bleeding at low altitude, minor bleeding after acute exposure to HA, and major bleeding after acute exposure to HA. To produce minor and major bleeding, 10% and 30% of the total blood volume was removed, respectively. At designated time points, samples were taken for laboratory examination. Results: While minor bleeding at low altitude led to minor coagulo-fibrinolytic derangements, it led to complicated derangements at HA, which presented as an early hypercoagulable state and transition to hypocoagulable and hyperfibrinolytic states with lower clot firmness. Major bleeding at HA resulted in greater derangements of the R time, K values, the D-dimer concentration, the alpha angle, maximum amplitude, and the concentration of fibrinogen than were observed at low altitude. Conclusions: The extent of coagulo-fibrinolytic derangements due to bleeding in rabbits after acute exposure to HA was more severe and complicated than that at low altitude. Therefore, proper resuscitation should be applied based on these changes.

Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing.

Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

Characterization of Combined Blast- and Fragment-Induced Pelvic Injuries and Hemostatic Resuscitation in Rabbits.

INTRODUCTION: To establish a blast- and fragment-induced pelvic injury animal model in rabbits, observe its injury characteristics, and explore the effects of hemostatic resuscitation combined with damage control surgery (DCS) with respect to this injury model. METHODS: Forty-eight rabbits were randomly allocated to four groups: group A rabbits were subjected to pelvic injury, group B rabbits to pelvic injury + DCS, group C rabbits to pelvic injury + DCS + resuscitation with Hextend, and group D rabbits to pelvic injury + DCS + Hextend + hemostatic resuscitation with tranexamic acid, fibrinogen concentrate, and prothrombin complex concentrate. Simulated blast and fragment-induced pelvic injury was produced by a custom-made machine. We implemented CT scanning and necropsy to assess the injury state and calculated the coefficient of variation (CV) of the cumulative abbreviated injury scale (AIS) to assess the reproducibility of the animal model. Immediately after instrumentation (0 h), and 1 h, 2 h, 4 h, and 8 h after injury, blood samples were taken for laboratory tests. RESULTS: We found that severe pelvic injury was produced with an AIS CV value of 10.32%, and the rabbits demonstrated severe physiologic impairment and coagulo-fibrinolytic derangements with high mortality. In rabbits of group D, however, physiologic and coagulo-fibrinolytic parameters were significantly enhanced with improved organ function and lowered mortality when compared with the other three groups. CONCLUSIONS: We herein established in rabbits a blast- and fragment-induced pelvic injury animal model that exhibited high reproducibility, and we demonstrated that hemostatic resuscitation plus DCS was effective in improving the outcome.

Hemostatic Effects of Bio-Zeolite Gauze and QuikClot Combat Gauze on Major Bleeding in Rabbits Acutely Exposed to High Altitude.

Objective: Hemostatic gauze application is an effective way to control major bleeding, which is the most common cause of death in trauma in both civilian and military settings. Coagulation derangement after acute exposure to high altitude might alter the effects of hemostatic gauzes. The present study aimed to observe the hemostatic effects of bio-zeolite gauze (BZG) and QuikClot Combat Gauze® (QCG) on major bleeding in rabbits acutely exposed to high altitude.Methods: Sixty rabbits were randomly and evenly divided into six groups. Animal models of simulated blast- and fragment-induced inguinal major bleeding were prepared in lower altitude and high-altitude areas, and BZG, QCG, and ordinary gauze without hemostatic material were used to control bleeding. The primary outcomes included immediate hemostasis rate, blood loss, and survival rate, while the secondary outcomes included hemodynamic parameters, laboratory examinations, and coagulation-relevant markers.Results: The overall effects of BZG and QCG were better than those of ordinary gauze, with a higher immediate hemostatic rate, less blood loss, and higher survival rate at 90 min after gauze application and higher red blood cell and platelet counts and lower creatinine level at 30 min after gauze application in lower altitude. The concentrations of coagulation factor XII and factor X in rabbits acutely exposed to high altitude were significantly lower than those in lower altitude. At high altitude, the hemostatic effects of BZG did not decrease significantly compared to those in the lower altitude, whereas those of ordinary gauze and QCG decreased significantly at high altitude compared to those in the lower altitude.Conclusions: Coagulation derangement after acute exposure to high altitude has negative effects on ordinary gauze and QCG but has no significant negative hemostatic effects on BZG.

Animal model-based simulation training for three emergent and urgent operations of penetrating thoracic injuries.

PURPOSE: To develop animal models of penetrating thoracic injuries and to observe the effects of the animal model-based training on improving the trainees' performance for emergent and urgent thoracic surgeries. METHODS: With a homemade machine, animal models of lung injuries and penetrating heart injuries were produced in porcine and used for training of chest tube drainage, urgent sternotomy, and emergent thoracotomy. Coefficient of variation of abbreviated injury scale and blood loss was calculated to judge the reproducibility of animal models. Five operation teams from basic-level hospitals (group A) and five operation teams from level III hospitals (group B) were included to be trained and tested. Testing standards for the operations were established after thorough literature review, and expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Tests were carried out after the training. Pre- and post-training performances were compared. Post-training survey using 7-point Likert scale was taken to evaluate the feelings of the trainees to these training approaches. RESULTS: Animal models of the three kinds of penetrating chest injuries were successfully established and the coefficient of variation of abbreviated injury scale and blood loss were all less than 25%. After literature review, testing standards were established, and expert questionnaire results showed that the scientific score was 7.30 ± 1.49, and the feasibility score was 7.50 ± 0.89. Post-training performance was significantly higher in both group A and group B than pre-training performance. Post-training survey showed that all the trainees felt confident in applying the operations and were generally agreed that the training procedure were very helpful in improving operation skills for thoracic penetrating injury. CONCLUSIONS: Animal model-based simulation training established in the current study could improve the trainees' performance for emergent and urgent thoracic surgeries, especially of the surgical teams from basic-level hospitals.

A Novel Scenario-Based, Mixed-Reality Platform for Training Nontechnical Skills of Battlefield First Aid: Prospective Interventional Study.

BACKGROUND: Although battlefield first aid (BFA) training shares many common features with civilian training, such as the need to address technical skills and nontechnical skills (NTSs), it is more highly scenario-dependent. Studies into extended reality show clear benefits in medical training; however, the training effects of extended reality on NTSs, including teamwork and decision-making in BFA, have not been fully proven. OBJECTIVE: The current study aimed to create and test a scenario-based, mixed-reality platform suitable for training NTSs in BFA. METHODS: First, using next-generation modeling technology and an animation synchronization system, a 10-person offensive battle drill was established. Decision-making training software addressing basic principles of tactical combat casualty care was constructed and integrated into the scenarios with Unreal Engine 4 (Epic Games). Large-space teamwork and virtual interaction systems that made sense in the proposed platform were developed. Unreal Engine 4 and software engineering technology were used to combine modules to establish a mixed-reality BFA training platform. A total of 20 Grade 4 medical students were recruited to accept BFA training with the platform. Pretraining and posttraining tests were carried out in 2 forms to evaluate the training effectiveness: one was knowledge acquisition regarding the NTS and the other was a real-world, scenario-based test. In addition, the students were asked to rate their agreement with a series of survey items on a 5-point Likert scale. RESULTS: A battlefield geographic environment, tactical scenarios, scenario-based decision software, large-space teamwork, and virtual interaction system modules were successfully developed and combined to establish the mixed-reality training platform for BFA. The posttraining score of the students' knowledge acquisition was significantly higher than that of pretraining (t=-12.114; P≤.001). Furthermore, the NTS score and the total score that the students obtained in the real-world test were significantly higher than those before training (t=-17.756 and t=-21.354, respectively; P≤.001). However, there was no significant difference between the scores of technical skills that the students obtained before and after training. A posttraining survey revealed that the students found the platform helpful in improving NTSs for BFA, and they were confident in applying BFA skills after training. However, most trainees thought that the platform was not helpful for improving the technical skills of BFA, and 45% (9/20) of the trainees were not satisfied with the simulation effect. CONCLUSIONS: A scenario-based, mixed-reality platform was constructed in this study. In this platform, interaction of the movement of multiple players in a large space and the interaction of decision-making by the trainees between the real world and the virtual world were accomplished. The platform could improve the NTSs of BFA. Future works, including improvement of the simulation effects and development of a training platform that could effectively improve both the technical skills and NTSs of BFA, will be carried out.

Time Course of Coagulo-Fibrinolytic Derangements During Acclimatization to High Altitude in Rabbits and a Preliminary Study on the Possible Mechanisms.

Zhong, Xin, Zhao Ye, Xiaolin Zhou, Renqing Jiang, Yijun Jia, Wenqiong Du, Haoyang Yang, Lin Zhang, Bai Lu, and Zhaowen Zong. Time course of coagulo-fibrinolytic derangements during acclimatization to high altitude in rabbits and a preliminary study on the possible mechanisms. High Alt Med Biol. 23:240-248, 2022. Background: Conflicting data exist regarding changes in the coagulation system during acclimatization to high altitude (HA), which makes the prevention of thromboembolic events difficult. The present study aimed at observing the dynamic changes in the coagulo-fibrinolysis system during acclimatization to HA and at exploring the possible mechanisms. Materials and Methods: Twenty rabbits of both sexes were randomly divided into two groups, including group A rabbits (healthy plain controls) and group B rabbits (acutely exposed to HA). A traditional coagulation test, thromboelastography analysis, and full blood cell count were used to assess the coagulo-fibrinolytic changes at different time points. Plasma was collected to examine the levels of relevant biomarkers. Results: Six hours and 1 day after acute exposure to HA, the coagulo-fibrinolytic system demonstrated a hypercoagulable state. Further, 3 days after exposure to HA, group B rabbits showed hypocoagulability, increased fibrinolysis, and lower clot firmness and 7 days after exposure to HA, delayed coagulation, decreased fibrinolysis, and increased clot firmness were observed. Subsequently, 14, 21, and 28 days after exposure to HA, we found increased clot firmness. Increased platelet counts and concentrations of fibrinogen and plasminogen activator inhibitor-1 contributed to this change. Conclusion: The coagulo-fibrinolytic derangements during acclimatization to HA in rabbits demonstrated a dynamic pattern.

Establishment of a combat damage control surgery training platform for explosive combined thoraco-abdominal injuries.

PURPOSE: It is challenging to prepare military surgeons with the skills of combat damage control surgery (CDCS). The current study aimed to establish a damage control surgery (DCS) training platform for explosive combined thoraco-abdominal injuries. METHODS: The training platform established in this study consisted of 3 main components: (1) A 50 m × 50 m square yard was constructed as the explosion site. Safety was assessed through cameras. (2) Sixteen pigs were injured by an explosion of trinitrotoluene attached with steel balls and were randomly divided into the DCS group (accepted DCS) and the control group (have not accepted DCS). The mortality rate was observed. (3) The literature was reviewed to identify the key factors for assessing CDCS, and testing standards for CDCS were then established. Expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Then, a 5-day training course with incorporated tests was used to test the efficacy of the established platform. In total, 30 teams attended the first training course. The scores that the trainees received before and after the training were compared. SPSS 11.0 was employed to analyze the results. RESULTS: The high-speed video playback confirmed the safety of the explosion site as no explosion fragments projected beyond the wall. No pig died within 24 h when DCS was performed, while 7 pigs died in the control group. After a literature review, assessment criteria for CDCS were established that had a total score of 100 points and had 4 major parts: leadership and team cooperation, resuscitation, surgical procedure, and final outcome. Expert questionnaire results showed that the scientific score was 8.6 ± 1.25, and the feasibility score was 8.74 ± 1.19. When compared with the basic level, the trainees' score improved significantly after training. CONCLUSION: The platform established in this study was useful for CDCS training.

Method for Teaching Life-Saving Combat First-Aid Skills With live-actor Patients Using a Wearable Training Apparatus.

INTRODUCTION: Training combat personnel in combat first-aid skills has faced many challenges over time, such as the need to combine tactics with medicine and to overcome combat personnel's lack of medical background knowledge. Therefore, many simulation methods are currently being developed, each of which has its advantages and disadvantages. In this study, a combined simulation method involving live-actor patients using a wearable training apparatus was developed, and the effects of this method were observed. MATERIALS AND METHODS: Focusing on the major causes of preventable deaths among victims killed in action, wearable training apparatuses simulating massive hemorrhage, airway obstruction, and tension pneumothorax were designed and produced. Methods of simulating these three injury types using live-actor patients with these training apparatuses were developed, and medical teachers evaluated the simulation effects. The live-actor patients were incorporated into a tactical scenario to train and test nonmedical and medical students in year 3, respectively. High-fidelity simulator-based training and traditional training without simulation served as the control. A post-training survey using a 7-point Likert scale evaluated the trainees' feelings toward these training approaches. RESULTS: Three types of training apparatuses were developed to simulate three life-threatening injuries, and the simulation effects of the live-actor patients using these apparatuses were highly recognized by medical teachers. Both live-actor patients and high-fidelity simulator-based training improved performance significantly more than traditional training. However, the improvement due to training with live-actor patients was greater than that due to high-fidelity simulator-based training for nonmedical students, whereas there was no difference between these two simulation methods for medical students. A post-training survey revealed that all the trainees were confident in practicing first-aid skills after training, and they all agreed that live-actor patients could combine tactical situations with first aid better than high-fidelity simulators. The nonmedical students strongly agreed that live-actor patients were more helpful in the training of injury evaluation than high-fidelity simulators. CONCLUSIONS: The method using wearable training apparatus-based live-actor patients was satisfying and effective for teaching life-saving combat first-aid skills, especially for nonmedical students.