RESUMEN
The capability to produce suture material using three-dimensional (3D) printing technology may have applications in remote health facilities where rapid restocking of supplies is not an option. This is a feasibility study evaluating the usability of 3D-printed sutures in the repair of a laceration wound when compared with standard suture material. The 3D-printed suture material was manufactured using a fused deposition modelling 3D printer and nylon 3D printing filament. Study participants were tasked with performing laceration repairs on the pigs' feet, first with 3-0 WeGo nylon suture material, followed by the 3D-printed nylon suture material. Twenty-six participants were enrolled in the study. Survey data demonstrated statistical significance with how well the 3D suture material performed with knot tying, 8.9 versus 7.5 (p = 0.0018). Statistical significance was observed in the 3D-printed suture's ultimate tensile strength when compared to the 3-0 Novafil suture (274.8 vs. 199.8 MPa, p = 0.0096). The 3D-printed suture also demonstrated statistical significance in ultimate extension when compared to commercial 3-0 WeGo nylon suture (49% vs. 37%, p = 0.0215). This study was successful in using 3D printing technology to manufacture suture material and provided insight into its usability when compared to standard suture material.
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Estudios de Factibilidad , Impresión Tridimensional , Técnicas de Sutura , Suturas , Resistencia a la Tracción , Animales , Porcinos , Laceraciones/cirugía , Ensayo de Materiales , Nylons , Cicatrización de Heridas , Humanos , Modelos Animales de EnfermedadRESUMEN
INTRODUCTION: In United States, health care workers have been immersed in the COVID-19 pandemic since February 2020. Since availability of COVID-19 vaccines, there is limited literature investigating the incidence of unknown COVID-19 infections in physicians and Advanced Practitioner Providers (APPs) working in emergency departments (EDs). The primary objective is to determine the incidence unknown COVID-19 infection within a cohort of emergency physicians (EPs) and APPs. METHODS: Prospective observational study at a tertiary academic center with emergency medicine residency and 64,000 annual ED visits. EPs/APPs providing care to ED patients over the prior 12 months were eligible. Serum samples were collected between May 1 and June 30, 2022. Analysis utilized Luminex xMAP® SARS-CoV-2 Multi-Antigen IgG Assay for antibodies to Nucleocapsid, Receptor-binding domain, and Spike subunit 1. Mean Fluorescent Intensity (MFI) ≥ 700 was considered positive. Subjects completed 12 question survey assessing demographics and previously confirmed COVID-19 infection. Fisher's exact test evaluated associations of demographics and clinical characteristics with confirmed COVID-19 status. Analyses performed using SAS, Version 9.4. P < 0.05 considered statistically significant. RESULTS: Sixty-nine of 81 eligible subjects (85.2%) participated, 58.0% were male, 97.1% white, with mean age of 37. Eighteen subjects had MFI ≥ 700 strongly suggestive of prior infection, with 17.7% unknown. No statistically significant difference between age, gender, race, children in home, or household member with previously COVID-19 infection. CONCLUSION: Unknown previous COVID-19 infection was less then expected in this cohort of EPs/APPs, and no association with individual characteristics, previously infected household member, or children in the home.
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COVID-19 , Médicos , Niño , Humanos , Masculino , Estados Unidos/epidemiología , Adulto , Femenino , COVID-19/epidemiología , SARS-CoV-2 , Vacunas contra la COVID-19 , Pandemias/prevención & control , Incidencia , Anticuerpos Antivirales , Inmunoglobulina GRESUMEN
BACKGROUND: The nasopharyngeal swab is the gold standard collection method for COVID-19, but is invasive and painful, subsequently resulting in poor patient acceptance. This investigation explores the process of developing and validating an alternative respiratory pathogen collection device that relies on a nasopharyngeal irrigation mechanic. The primary objective was to determine if sufficient pathological sampling can be achieved by mechanism of nasopharyngeal irrigation that is proportionate to the nasopharyngeal swab method. METHODS: The study device was designed using Shapr3D modeling software and fabricated on a fused deposition modeling printer. Fifteen participants were enrolled with each receiving a saline nasopharyngeal washing using the study device. Specimen adequacy was evaluated by two real-time reverse transcriptase polymerase chain reaction (PCR) testing methods to identify the presence of the human RNase P gene. Results were evaluated quantitatively through interpretation of the PCR cycle threshold (Ct). RESULTS: All 15 specimens tested positive for the presence of RNaseP, demonstrating specimen cellularity, adequate extraction of nucleic acids, and the absence of inhibitors to amplification. The mean Ct value was 29.5 (Applied Biosystems TaqPath RT-qPCR) and 30.7 (NECoV19). All participants felt the study device irrigation procedure was faster than the nasopharyngeal swab, with none experiencing any discomfort from the irrigation mechanism. CONCLUSION: The importance of early diagnostic testing and its role in countermeasures for communicable diseases such as COVID-19 is well established in the literature. Innovation to bolster our testing infrastructure is more important now than ever. This study was successful in developing and validating an alternative nasopharyngeal respiratory pathogen collection device that utilizes fluid debridement as its core mechanic. Data from this pilot study demonstrated the study device was successful in producing high-quality specimens for PCR testing. Feedback from the study participants was also in favor of the study device when compared to the nasopharyngeal swab.
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COVID-19 , Ácidos Nucleicos , Humanos , Pandemias , Proyectos Piloto , COVID-19/diagnóstico , COVID-19/epidemiología , Ribonucleasa P/genética , SARS-CoV-2 , Nasofaringe , Manejo de Especímenes/métodos , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Cardiac sympathetic overactivation is involved in arrhythmogenesis in patients with chronic heart failure (CHF). Inflammatory infiltration in the stellate ganglion (SG) is a critical factor for cardiac sympathoexcitation in patients with ventricular arrhythmias. This study aims to investigate if macrophage depletion in SGs decreases cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF. Surgical ligation of the coronary artery was used for induction of CHF. Clodronate liposomes were microinjected into bilateral SGs of CHF rats for macrophage depletion. Using cytokine array, immunofluorescence staining, and Western blot analysis, we found that macrophage expansion and expression of TNFα and IL-1ß in SGs were markedly increased in CHF rats. Flow cytometry data confirmed that the percentage of macrophages in SGs was higher in CHF rats than that in sham rats. Clodronate liposomes significantly reduced CHF-elevated proinflammatory cytokine levels and macrophage expansion in SGs. Clodronate liposomes also reduced CHF-increased N-type Ca2+ currents and excitability of cardiac sympathetic postganglionic neurons and inhibited CHF-enhanced cardiac sympathetic nerve activity. ECG data from 24-h, continuous telemetry recording in conscious rats demonstrated that clodronate liposomes not only restored CHF-induced heterogeneity of ventricular electrical activities, but also decreased the incidence and duration of ventricular tachycardia/fibrillation in CHF. Macrophage depletion with clodronate liposomes attenuated CHF-induced cardiac sympathetic overactivation and ventricular arrhythmias through reduction of macrophage expansion and neuroinflammation in SGs.
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Antiinflamatorios/farmacología , Ácido Clodrónico/farmacología , Insuficiencia Cardíaca/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Corazón/inervación , Macrófagos/efectos de los fármacos , Enfermedades Neuroinflamatorias/prevención & control , Ganglio Estrellado/efectos de los fármacos , Taquicardia Ventricular/prevención & control , Fibrilación Ventricular/prevención & control , Potenciales de Acción , Animales , Canales de Calcio Tipo N/metabolismo , Señalización del Calcio , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Mediadores de Inflamación/metabolismo , Interleucina-1beta/metabolismo , Liposomas , Macrófagos/metabolismo , Masculino , Enfermedades Neuroinflamatorias/etiología , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/fisiopatología , Ratas Sprague-Dawley , Ganglio Estrellado/metabolismo , Ganglio Estrellado/fisiopatología , Taquicardia Ventricular/etiología , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/fisiopatología , Factor de Necrosis Tumoral alfa/metabolismo , Fibrilación Ventricular/etiología , Fibrilación Ventricular/metabolismo , Fibrilación Ventricular/fisiopatologíaRESUMEN
INTRODUCTION: As a result of the COVID-19 pandemic and highly contagious nature of SARS-CoV-2, emergency departments (EDs) have been forced to implement new measures and protocols to minimize the spread of the disease within their departments. The primary objective of this study was to determine if the implementation of a designated COVID-19 cohort area (hot zone) within a busy ED mitigated the dissemination of SARS-CoV-2 throughout the rest of the department. METHODS: In an ED of a tertiary academic medical center, with 64,000 annual visits, an eight room pod was designated for known COVID-19 or individuals with high suspicion for infection. There was a single entry and exit for donning and doffing personal protective equipment (PPE). Health care workers (HCW) changed gowns and gloves between patients, but maintained their N-95 mask and face shield, cleaning the shield with a germicidal wipe between patients. Staffing assignments designated nurses and technicians to remain in this area for 4 h, where physicians regularly moved between the hot zone and rest of the ED. Fifteen surface samples and four air samples were taken to evaluate SARS-CoV-2 contamination levels and the effectiveness of infection control practices. Samples were collected outside of patient rooms in 3 primary ED patient care areas, the reception area, the primary nurses station, inside the cohort area, and the PPE donning and doffing areas immediately adjacent. Samples were recovered and analyzed for the presence of the E gene of SARS-CoV-2 using RT-PCR. RESULTS: SARS-CoV-2 was not detected on any surface samples, including in and around the cohort area. All air samples outside the COVID-19 hot zone were negative for SARS-CoV-2, but air samples within the cohort area had a low level of viral contamination. CONCLUSION: A designated COVID-19 cohort area resulted in no air or surface contamination outside of the hot zone, and only minimal air, but no surface contamination, within the hot zone.
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COVID-19/prevención & control , COVID-19/transmisión , Servicio de Urgencia en Hospital , Control de Infecciones/métodos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , COVID-19/epidemiología , Guantes Protectores , Personal de Salud , Humanos , Habitaciones de Pacientes , Equipo de Protección Personal , Ropa de Protección , Dispositivos de Protección Respiratoria , SARS-CoV-2 , Manejo de Especímenes , Centros de Atención TerciariaRESUMEN
BACKGROUND: Nurses are the primary clinicians who collect specimens for respiratory tract infection testing. The specimen collection procedure is time and resource-consuming, but more importantly, it places nurses at risk for potential infection. The practice of allowing patients to self-collect their diagnostic specimens may provide an alternative testing model for the current COVID-19 outbreaks. The objective of this paper was to evaluate the accuracy and patient perception of self-collected specimens for respiratory tract infection diagnostics. METHODS: A concise clinical review of the recently published literature was conducted. RESULTS: A total of 11 articles were included the review synthesis. The concept of self-collected specimens has a high patient acceptance rate of 83-99%. Self-collected nasal-swab specimens demonstrated strong diagnostic fidelity for respiratory tract infections with a sensitivity between 80-100%, this is higher than the 76% sensitivity observed with self-collected throat specimens. In a comparative study evaluating a professionally collected to a self-collected specimen for COVID-19 testing, a high degree of agreement (k = 0.89) was observed between the two methods. CONCLUSION: As we continue to explore for testing models to combat the COVID-19 pandemic, self-collected specimens is a practical alternative to nurse specimen collection.
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COVID-19/diagnóstico , Infecciones del Sistema Respiratorio/diagnóstico , Manejo de Especímenes/normas , COVID-19/epidemiología , Prueba de COVID-19 , Servicio de Urgencia en Hospital , Humanos , Pandemias , SARS-CoV-2 , Manejo de Especímenes/métodosRESUMEN
INTRODUCTION: Frostbite is thought to result from initial vasoconstriction, ischemia, intracellular ice crystal formation, and inflammation caused by reperfusion injury. Corticosteroids have demonstrated beneficial anti-inflammatory effects in the treatment of other ischemia/reperfusion clinical conditions. The objective of this study was to determine the effect of dexamethasone (dex) on wound healing, inflammatory response, and vasculogenesis in a mouse skin frostbite model. METHODS: Treatment and control groups of C57/BL6 mice were subjected to frostbite using a previously described model. Treatment with intraperitoneal dex (1 mg·kg-1·d-1) began on the day of frostbite induction and lasted for 7 d. Over 4 wk, we compared wound diameter; morphology by visual inspection, hematoxylin-eosin staining, and Masson's trichrome staining; density of inflammatory cytokines IL-1ß and TNFα using Western blot analysis; and formation of microvasculature using immunofluorescence staining. Data were analyzed using 1-way or 1-way repeated-measures analysis of variance. RESULTS: After frostbite injury, morphological images demonstrated epidermal necrosis and loss in the frostbitten skin as well as infiltration of inflammation-related leukocytes. Increased production of inflammatory cytokines and disappearance of the microvasculature also occurred in the frostbitten skin. In comparison to the control group, treatment with dex promoted wound healing as demonstrated by decreased wound diameter; decreased levels of inflammatory cytokines, and accelerated formation of mature microvasculature. CONCLUSIONS: In this animal model, dex improved wound healing in frostbitten skin and demonstrated both anti-inflammatory effects and stimulation of vasculogenesis. This study suggests that the use of potent anti-inflammatory agents may be an effective strategy for mitigating frostbite injury.
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Antiinflamatorios/farmacología , Dexametasona/uso terapéutico , Congelación de Extremidades/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Neovascularización Fisiológica/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Animales , Ratones , Ratones Endogámicos C57BL , Piel/patologíaRESUMEN
Komodo dragons (Varanus komodoensis) are large lizards known to take down prey even larger than themselves. They rarely attack humans. A 38-year-old woman was bitten by a Komodo dragon on her hand while cleaning its enclosure. She was transiently hypotensive. The wounds were extensively cleaned, and she was started on prophylactic antibiotics. Her wounds healed without any infectious sequelae. Komodo dragon bites are historically thought to be highly infectious and venomous. Based on a literature review, neither of these are likely true. As in any bite, initial stabilization followed by wound management are the main components to therapy.
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Mordeduras y Picaduras , Lagartos , Adulto , Animales , Animales de Zoológico , Femenino , Humanos , Heridas y Lesiones/terapiaRESUMEN
INTRODUCTION: Due to the recent Ebola virus outbreak in West Africa, patients with epidemiologic risk for Ebola virus disease and symptoms consistent with Ebola virus disease are presenting to emergency departments (EDs) and clinics in the United States. These individuals, identified as a person under investigation for Ebola virus disease, are initially screened using a molecular assay for Ebola virus. If this initial test is negative and the person under investigation has been symptomatic for < 3 days, a repeat test is required after 3 days of symptoms to verify the negative result. In the time interval before the second test result is available, manifestations of the underlying disease process for the person under investigation, whether due to Ebola virus disease or some other etiology, may require further investigation to direct appropriate therapy. MATERIALS AND METHODS: ED administrators, physicians, and nurses proposed processes to provide care that is consistent with other ED patients. Biocontainment unit administrators, industrial hygienists, laboratory directors, physicians, and other medical personnel examined the ED processes and offered biocontainment unit personal protective equipment and process strategies designed to ensure safety for providers and patients. CONCLUSION: ED processes for the safe and timely evaluation and management of the person under investigation for Ebola virus disease are presented with the ultimate goals of protecting providers and ensuring a consistent level of care while confirmatory testing is pending.
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Servicio de Urgencia en Hospital , Fiebre Hemorrágica Ebola/diagnóstico , Servicio de Urgencia en Hospital/normas , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/terapia , Humanos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Aislamiento de Pacientes/métodos , Aislamiento de Pacientes/normas , Ropa de Protección/normas , Estados UnidosRESUMEN
BACKGROUND: Pancreatitis is a common diagnosis in the emergency department (ED), and milk-alkali syndrome (MAS) is an uncommon etiology for pancreatitis. MAS is caused by increased calcium and alkali ingestion, causing hypercalcemia accompanied by metabolic alkalosis and renal failure. Once considered rare, MAS is an increasingly common cause of hypercalcemia. Awareness of the resurgence of this syndrome is important for emergency physicians when recalling the causes of renal failure and pancreatitis. We present a case of pancreatitis and acute renal failure (ARF) in a chronically hypocalcemic DiGeorge syndrome patient, resulting from hypercalcemia secondary to excessive ingestion of calcium carbonate tablets. CASE REPORT: A patient with DiGeorge syndrome and chronic abdominal pain due to gastroesophageal reflux disease (GERD) presented to our ED for severe abdominal pain. He reported nausea and vomiting, as well as epigastric pain that seemed worse than his typical pain. Laboratory evaluation revealed pancreatitis and ARF, although the patient had no prior history of these conditions. Upon further questioning, his mother divulged that the patient had been taking large quantities of calcium carbonate tablets for his worsening GERD symptoms. The patient was admitted to the intensive care unit where his pancreatitis and ARF eventually resolved as his calcium levels returned to his baseline. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: MAS is a relatively uncommon diagnosis, but can lead to serious sequelae such as pancreatitis and ARF. Questioning the patient about calcium ingestion is an important facet to the diagnosis and work-up of pancreatitis and ARF. Recognition of this etiology can improve patient outcomes and prevent recurrences.
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Lesión Renal Aguda/etiología , Síndrome de DiGeorge/complicaciones , Hipercalcemia/complicaciones , Pancreatitis/etiología , Adulto , Enfermedad Crónica , Humanos , Hipercalcemia/diagnóstico , Hipocalcemia/etiología , MasculinoRESUMEN
The Institute of Medicine's 2006 report titled "Hospital-Based Emergency Care: At the Breaking Point" called national attention to the lack of specialty-trained emergency care practitioners, particularly in rural America. One suggested strategy for narrowing the gap between the prevalence of residency-trained, board-certified emergency physicians practicing in rural and urban emergency departments is the development of rural clinical experiences for emergency medicine residents during the course of their training. This article addresses promotion of a rural emergency medicine rotation to hospital leadership and resident recruits, examines funding sources, discusses medical liability and disability insurance options, provides suggestions for meeting faculty and planned educational activity residency review committee requirements, and offers guidance about site selection to direct emergency medicine academic leaders considering or planning a new rural emergency medicine rotation.
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Medicina de Emergencia/educación , Hospitales Rurales , Internado y Residencia/organización & administración , Servicio de Urgencia en Hospital/organización & administración , Servicio de Urgencia en Hospital/estadística & datos numéricos , Docentes Médicos , Humanos , Internado y Residencia/métodos , Población Rural , Estados UnidosRESUMEN
This work describes the use of a new intubation device, the intubating laryngeal tube (iLTA) as developed by Boedeker. Emergency Department residents and staff from the University of Nebraska Medical Center performed intubations using the Laerdal Difficult Airway Trainer Manikin(TM). The participants' perceived value of the intubating laryngeal tube as well as its efficacy in intubation performance were measured and found to be highly favorable.
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Intubación Intratraqueal/instrumentación , Intubación Intratraqueal/métodos , Laringe , Maniquíes , Satisfacción del Paciente , Diseño de Equipo , Análisis de Falla de Equipo , HumanosRESUMEN
Lightly embalmed hemorrhagic cadaver models and the Storz CMAC videolaryngoscope fitted with either an integrated suction blade vs. a traditional blade were used to determine efficacy of the instruments in hemorrhagic airway intubation. Significant differences were found between the devices in intubation success rates of the viscosity saliva and frothy blood models, as well as a significant difference in intubation times in the frothy blood model. Feedback provided by the study participants indicated preference for the integrated video suction blade in hemorrhagic airway intubation.
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Hemorragia/terapia , Intubación Intratraqueal/instrumentación , Laringoscopios , Enfermedades Pulmonares/terapia , Succión/instrumentación , Cirugía Asistida por Computador/instrumentación , Grabación en Video/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Humanos , Intubación Intratraqueal/métodos , Integración de Sistemas , Interfaz Usuario-ComputadorRESUMEN
This work describes the use of Adobe Connect software along with algorithm software to provide the necessary audio visual communication platform for telementoring a complex medical procedure to novice providers located at a distant site.
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Personal Militar/educación , Enseñanza/métodos , Telemedicina , Recursos Audiovisuales , Proyectos Piloto , GuerraRESUMEN
Peripheral arterial disease (PAD) is a common circulatory problem in lower extremities, and the murine ischemic model is used to reproduce human PAD. To compare strain differences of skeletal muscle responses to ischemia, the left femoral artery was blocked by ligation to reduce blood flow to the limb of BALB/c and C57BL/6 mice. After 6 weeks of the femoral artery ligation, the functional and morphological changes of the gastrocnemius muscle were evaluated. BALB/c mice displayed serious muscular dystrophy, including smaller myofibers (524.3 ± 66 µM2), accumulation of adipose-liked tissue (17.8 ± 0.9%), and fibrosis (6.0 ± 0.5%), compared to C57BL/6 mice (1,328.3 ± 76.3 µM2, 0.27 ± 0.09%, and 1.56 ± 0.06%, respectively; p < 0.05). About neuromuscular junctions (NMJs) in the gastrocnemius muscle, 6 weeks of the femoral artery ligation induced more damage in BALB/c mice than that in C57BL/6 mice, demonstrated by the fragment number of nicotinic acetylcholine receptor (nAChR) clusters (8.8 ± 1.3 in BALB/c vs. 2.5 ± 0.7 in C57BL/6 mice, p < 0.05) and amplitude of sciatic nerve stimulated-endplate potentials (EPPs) (9.29 ± 1.34 mV in BALB/c vs. 20.28 ± 1.42 mV in C57BL/6 mice, p < 0.05). More importantly, 6 weeks of the femoral artery ligation significantly weakened sciatic nerve-stimulated skeletal muscle contraction in BALB/c mice, whereas it didn't alter the skeletal muscle contraction in C57BL/6 mice. These results suggest that the femoral artery ligation in BALB/c mice is a useful animal model to develop new therapeutic approaches to improve limb structure and function in PAD, although the mechanisms about strain differences of skeletal muscle responses to ischemia are unclear.
RESUMEN
During tourniquet application, blood flow is restricted to a limb to stop excessive limb hemorrhage in a trauma setting and to create a bloodless operating field in the surgical setting. During tourniquet-related ischemia, aerobic respiration stops, and ATP is depleted, and during subsequent reperfusion, there is an increase in reactive oxygen species (ROS) production and other endogenous substances, which leads to acute ischemia-reperfusion (IR) injuries, including tissue necrosis and skeletal muscle contractile dysfunction. Hyperbaric oxygen (HBO) therapy can increase the arterial oxygen tension in the tissues of patients with general hypoxia/anoxia, including carbon monoxide poisoning, circulatory arrest, and cerebral and myocardial ischemia. Here, we studied the protective effects of HBO pretreatment with 100% oxygen at 2.5 ATA against tourniquet/IR injury in mice. After one hour of HBO therapy with 100% oxygen at 2.5 ATA was administered to C57/BL6 mice, a rubber band was placed at the hip joint of the unilateral hindlimb to induce 3 h of ischemia and then released for 48 h of reperfusion. We analyzed gastrocnemius muscle morphology and contractile function and measured the levels of ATP and ROS accumulation in the muscles. HBO pretreatment did not improve tourniquet/IR-injured gastrocnemius muscle morphology and muscle contraction. Tourniquet/IR mice with HBO pretreatment showed no increase in ATP levels in IR tissues, but they did have a decreased amount of ROS accumulation in the muscles, compared to IR mice with no HBO pretreatment. These data suggest that one hour of HBO pretreatment with 100% oxygen at 2.5 ATA increases the antioxidant response to lower ROS accumulation but does not increase ATP levels in IR muscles and improve tourniquet/IR-injured muscle morphology and contractile function.
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Oxigenoterapia Hiperbárica , Daño por Reperfusión , Animales , Humanos , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético , Daño por Reperfusión/prevención & control , TorniquetesRESUMEN
Tourniquets are widely used to stop extremity hemorrhage, but their use and subsequent release can result in nerve damage and degeneration, leading to neurological deficits. Increasing evidence has suggested a pivotal role of inflammation in nerve damage and abnormal mechanoreception. In this study, we investigated the therapeutic effects of masitinib (Mas), an anti-neuroinflammatory drug, on the mechanoreception of sensory neurons in a mouse model of tourniquet-induced hind paw ischemia-reperfusion (tourniquet/IR). C57BL/6 mice were subjected to 3 h of ischemia by placing a rubber band at the ankle joint and evaluated for subsequent reperfusion injury on day 1, 3, 7, 14, and 28 based on the experiments. Treatment with Mas (28 mg/kg/day, i.p.) began on the day of IR induction and lasted for 1, 3, 7, 14, or 28 days. Tourniquet/IR caused sensory nerve denervation in the skin of paw pads and abolished the hind paw mechanoreception to mechanical stimulation during the first 3 days of reperfusion. Sensory nerves gradually reinnervated in the skin of paw pads and allodynia began to appear on day 7. The maximum reaction occurred on day 14 and was maintained throughout the study period. Treatment with Mas mitigated nerve damage and improved hind paw mechanoreception to mechanical stimulation by decreasing the production of reactive oxygen species (ROS) during the early stages of tourniquet/IR. Mas also alleviated allodynia and decreased inflammatory cytokines (IL-1ß and TNFα) in the skin of paw pads from days 7-28. Our data suggest that treatment with Mas significantly ameliorated paw numbness and allodynia in mouse hind paw tourniquet/IR.
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TorniquetesRESUMEN
The tourniquet or femoral artery ligation is widely used to stop extremity hemorrhage or create a bloodless operating field in the combat scenario and civilian setting. However, these procedures with subsequent reperfusion also induce ischemia-reperfusion (IR) injuries. To fully evaluate animal models of limb IR injuries, we compared tourniquet- and femoral artery ligation-induced IR injuries in the hindlimb of mice. In C57/BL6 mice, 3 h of unilateral hindlimb ischemia was induced by placement of a rubber band at the hip joint or a surgical ligation of the femoral artery. The tourniquet or femoral artery ligation was then released, allowing for 24 h of reperfusion. Compared to the femoral artery ligation/IR, the tourniquet/IR induced more severe skeletal muscle damage, including muscle necrosis and interruption of muscle fibers. There was no gastrocnemius muscle contraction in tourniquet/IR, while femoral artery ligation/IR markedly weakened gastrocnemius muscle contraction. Motor nerve terminals disappeared, and endplate potentials (EPPs) were undetectable in tourniquet/IR, whereas femoral artery ligation/IR only induced mild impairment of motor nerve terminals and decreased the amplitude of EPPs. Additionally, western blot data showed that proinflammatory cytokine levels (IL-1ß and TNF-α) were higher in the tourniquet/IR than that in femoral artery ligation/IR. Moreover, tourniquet/IR caused significant tissue edema and dilation of lymphatic vessels in the hindlimb, compared to femoral artery ligation/IR. The above data demonstrated that tourniquet/IR-induced acute hindlimb injuries are more severe than those induced by femoral artery ligation/IR. This suggests that future investigators should determine which hindlimb IR model (tourniquet/IR or femoral artery ligation/IR) is optimal depending on the purpose of their study.
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Daño por Reperfusión , Torniquetes , Animales , Modelos Animales de Enfermedad , Arteria Femoral/cirugía , Miembro Posterior , Isquemia , Ligadura , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético , ReperfusiónRESUMEN
AIMS: Cardiac sympathetic overactivation is an important trigger of ventricular arrhythmias in patients with chronic heart failure (CHF). Our previous study demonstrated that N-type calcium (Cav2.2) currents in cardiac sympathetic post-ganglionic (CSP) neurons were increased in CHF. This study investigated the contribution of Cav2.2 channels in cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF. METHODS AND RESULTS: Rat CHF was induced by surgical ligation of the left coronary artery. Lentiviral Cav2.2-α shRNA or scrambled shRNA was transfected in vivo into stellate ganglia (SG) in CHF rats. Final experiments were performed at 14 weeks after coronary artery ligation. Real-time polymerase chain reaction and western blot data showed that in vivo transfection of Cav2.2-α shRNA reduced the expression of Cav2.2-α mRNA and protein in the SG in CHF rats. Cav2.2-α shRNA also reduced Cav2.2 currents and cell excitability of CSP neurons and attenuated cardiac sympathetic nerve activities (CSNA) in CHF rats. The power spectral analysis of heart rate variability (HRV) further revealed that transfection of Cav2.2-α shRNA in the SG normalized CHF-caused cardiac sympathetic overactivation in conscious rats. Twenty-four-hour continuous telemetry electrocardiogram recording revealed that this Cav2.2-α shRNA not only decreased incidence and duration of ventricular tachycardia/ventricular fibrillation but also improved CHF-induced heterogeneity of ventricular electrical activity in conscious CHF rats. Cav2.2-α shRNA also decreased susceptibility to ventricular arrhythmias in anaesthetized CHF rats. However, Cav2.2-α shRNA failed to improve CHF-induced cardiac contractile dysfunction. Scrambled shRNA did not affect Cav2.2 currents and cell excitability of CSP neurons, CSNA, HRV, and ventricular arrhythmogenesis in CHF rats. CONCLUSIONS: Overactivation of Cav2.2 channels in CSP neurons contributes to cardiac sympathetic hyperactivation and ventricular arrhythmogenesis in CHF. This suggests that discovering purely selective and potent small-molecule Cav2.2 channel blockers could be a potential therapeutic strategy to decrease fatal ventricular arrhythmias in CHF.