An evaluation of the usability and durability of 3D printed versus standard suture materials.

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.

Incidence of unknown COVID-19 infection in a cohort of emergency physicians and advance practice providers.

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.

Different responses of skeletal muscles to femoral artery ligation-induced ischemia identified in BABL/c and C57BL/6 mice.

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.

Pandemic driven innovation: A pilot evaluation of an alternative respiratory pathogen collection device.

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.

Hyperbaric oxygen therapy does not alleviate tourniquet-induced acute ischemia-reperfusion injury in mouse skeletal muscles.

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.

Therapeutic effects of masitinib on abnormal mechanoreception in a mouse model of tourniquet-induced extremity ischemia-reperfusion.

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.

A comparison of acute mouse hindlimb injuries between tourniquet- and femoral artery ligation-induced ischemia-reperfusion.

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.

Accuracy and Acceptance of a Self-Collection Model for Respiratory Tract Infection Diagnostics: A Concise Clinical Literature Review.

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.

Long-Term Assessment of the Effects of COVID-19 and Isolation Care on Survivor Disability and Anxiety.

We conducted an assessment of disability, anxiety, and other life impacts of COVID-19 and isolation care in a unique cohort of individuals. These included both community admissions to a university hospital as well as some of the earliest international aeromedical evacuees. Among an initial 16 COVID-19 survivors that were interviewed 6-12 months following their admission into isolation care, perception of their isolation care experience was related to their reporting of long-term consequences. However, anxiety and disability assessed with standard scores had no relationship with each other. Both capture of the isolation care experience and caution relying on single scoring systems for assessing long-term consequences in survivors are important considerations for on-going and future COVID-19 and other pandemic survivor research.

Implementation of a COVID-19 cohort area resulted in no surface or air contamination in surrounding areas in one academic emergency department.

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.

Macrophage depletion in stellate ganglia alleviates cardiac sympathetic overactivation and ventricular arrhythmogenesis by attenuating neuroinflammation in heart failure.

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.

Inhibition of N-type calcium channels in cardiac sympathetic neurons attenuates ventricular arrhythmogenesis in heart failure.

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.

Dexamethasone Improves Wound Healing by Decreased Inflammation and Increased Vasculogenesis in Mouse Skin Frostbite Model.

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.

Dexamethasone ameliorates recovery process of neuromuscular junctions after tourniquet-induced ischemia-reperfusion injuries in mouse hindlimb.

As a primary tool in first-line treatment of severe extremity hemorrhage, tourniquet and subsequent reperfusion also induce ischemia-reperfusion (IR) injuries including severe dysfunction of the neuromuscular junction (NMJ). Here, we observed the effect of dexamethasone (Dex) on NMJs suffering from IR-cause damage in mouse hindlimb. Unilateral hindlimb of mice was subjected to 3 h of tourniquet application by placing a rubber band, and then releasing the rubber band for reperfusion during different periods of time (1, 2, 4, and 6 weeks). Dex treatment (1 mg/kg/day, i.p.) began on the day of tourniquet-IR induction and lasted for 7 days. During tourniquet-induced IR, NMJs in gastrocnemius muscles showed significant morphological and functional changes. These changes include that motor nerve terminals gradually regenerated, even reaching that seen in sham mice; nicotinic acetylcholine receptor (nAChR) clusters were gradually fragmented with prolongation of reperfusion; and the amplitude of endplate potentials (EPPs) gradually increased, but it did not restore to the sham level at 6 weeks of tourniquet-induced IR. IL-1ß and TNFα were over-produced in gastrocnemius muscles at 1 week, gradually decreased to the sham level at 4 weeks, and returned back to a high level at 6 weeks of tourniquet-induced IR. Treatment with Dex mitigated fragmentation of nAChR clusters, increased the amplitude of EPPs, and decreased levels of TNFα and IL-1ß during the first two weeks of tourniquet-induced IR. The present study suggests that anti-inflammation is a potentially important strategy for promoting the morphological and functional recovery processes of NMJs after tourniquet-induced IR injuries.

Advanced Preparation Makes Research in Emergencies and Isolation Care Possible: The Case of Novel Coronavirus Disease (COVID-19).

The optimal time to initiate research on emergencies is before they occur. However, timely initiation of high-quality research may launch during an emergency under the right conditions. These include an appropriate context, clarity in scientific aims, preexisting resources, strong operational and research structures that are facile, and good governance. Here, Nebraskan rapid research efforts early during the 2020 coronavirus disease pandemic, while participating in the first use of U.S. federal quarantine in 50 years, are described from these aspects, as the global experience with this severe emerging infection grew apace. The experience has lessons in purpose, structure, function, and performance of research in any emergency, when facing any threat.

Crossover Assessment of Intraoral and Cuffed Ventilation by Emergency Responders.

OBJECTIVES: A cuffed bag valve mask (BVM) is the most common device used by emergency medical responders to ventilate patients. The BVM can be difficult for users to seal around the patient's mouth and nose. An intraoral mask (IOM) with snorkel-like design may facilitate quicker and better ventilation particularly under austere conditions. METHODS: Both a BVM and IOM were utilized by 27 trained emergency medical technicians and paramedics to ventilate a lightly embalmed cadaver. Ventilation efficacy, workload, and usability were assessed for both devices across four study conditions. RESULTS: The IOM was superior to the BVM in delivered tidal volume ratio (measure of leak, p < 0.03) and minute ventilation (p < 0.0001). Workload, ergonomic and usability assessments indicated that the IOM facilitated gripping through the reduced hand interface size (p < 0.01), decreased user effort (p < 0.001), and reduced upper limb workload (p = 0.0088). CONCLUSIONS: In the assessed model, the IOM represented a better choice for airway management than the standard cuffed BVM. An emergency medical device that is intuitive, efficacious and less demanding has the potential to reduce responder stress and improve resuscitation efforts, especially during austere rescue and patient transport.

Substrates and potential therapeutics of ventricular arrhythmias in heart failure.

Heart failure (HF) is a clinical syndrome characterized by ventricular contractile dysfunction. About 50% of death in patients with HF are due to fetal ventricular arrhythmias including ventricular tachycardia and ventricular fibrillation. Understanding ventricular arrhythmic substrates and discovering effective antiarrhythmic interventions are extremely important for improving the prognosis of patients with HF and reducing its mortality. In this review, we discussed ventricular arrhythmic substrates and current clinical therapeutics for ventricular arrhythmias in HF. Base on the fact that classic antiarrhythmic drugs have the limited efficacy, side effects, and proarrhythmic potentials, we also updated some therapeutic strategies for the development of potential new antiarrhythmic interventions for patients with HF.

Dexamethasone Protects Against Tourniquet-Induced Acute Ischemia-Reperfusion Injury in Mouse Hindlimb.

Extremity injuries with hemorrhage have been a significant cause of death in civilian medicine and on the battlefield. The use of a tourniquet as an intervention is necessary for treatment to an injured limb; however, the tourniquet and subsequent release results in serious acute ischemia-reperfusion (IR) injury in the skeletal muscle and neuromuscular junction (NMJ). Much evidence demonstrates that inflammation is an important factor to cause acute IR injury. To find effective therapeutic interventions for tourniquet-induced acute IR injuries, our current study investigated effect of dexamethasone, an anti-inflammatory drug, on tourniquet-induced acute IR injury in mouse hindlimb. In C57/BL6 mice, a tourniquet was placed on unilateral hindlimb (left hindlimb) at the hip joint for 3 h, and then released for 24 h to induce IR. Three hours of tourniquet and 24 h of release (24-h IR) caused gastrocnemius muscle injuries including rupture of the muscle sarcolemma and necrosis (42.8 ± 2.3% for infarct size of the gastrocnemius muscle). In the NMJ, motor nerve terminals disappeared, and endplate potentials were undetectable in 24-h IR mice. There was no gastrocnemius muscle contraction in 24-h IR mice. Western blot data showed that inflammatory cytokines (TNFα and IL-1ß) were increased in the gastrocnemius muscle after 24-h IR. Treatment with dexamethasone at the beginning of reperfusion (1 mg/kg, i.p.) significantly inhibited expression of TNFα and IL-1ß, reduced rupture of the muscle sarcolemma and infarct size (24.8 ± 2.0%), and improved direct muscle stimulation-induced gastrocnemius muscle contraction in 24-h IR mice. However, this anti-inflammatory drug did not improve NMJ morphology and function, and sciatic nerve-stimulated skeletal muscle contraction in 24-h IR mice. The data suggest that one-time treatment with dexamethasone at the beginning of reperfusion only reduced structural and functional impairments of the skeletal muscle but not the NMJ through inhibiting inflammatory cytokines.

Transition of Care from the Emergency Department to the Outpatient Setting: A Mixed-Methods Analysis.

INTRODUCTION: The goal of this study was to characterize current practices in the transition of care between the emergency department and primary care setting, with an emphasis on the use of the electronic medical record (EMR). METHODS: Using literature review and modified Delphi technique, we created and tested a pilot survey to evaluate for face and content validity. The final survey was then administered face-to-face at eight different clinical sites across the country. A total of 52 emergency physicians (EP) and 49 primary care physicians (PCP) were surveyed and analyzed. We performed quantitative analysis using chi-square test. Two independent coders performed a qualitative analysis, classifying answers by pre-defined themes (inter-rater reliability > 80%). Participants' answers could cross several pre-defined themes within a given question. RESULTS: EPs were more likely to prefer telephone communication compared with PCPs (30/52 [57.7%] vs. 3/49 [6.1%] P < 0.0001), whereas PCPs were more likely to prefer using the EMR for discharge communication compared with EPs (33/49 [67.4%] vs. 13/52 [25%] p < 0.0001). EPs were more likely to report not needing to communicate with a PCP when a patient had a benign condition (23/52 [44.2%] vs. 2/49 [4.1%] p < 0.0001), but were more likely to communicate if the patient required urgent follow-up prior to discharge from the ED (33/52 [63.5%] vs. 20/49 [40.8%] p = 0.029). When discussing barriers to effective communication, 51/98 (52%) stated communication logistics, followed by 49/98 (50%) who reported setting/environmental constraints and 32/98 (32%) who stated EMR access was a significant barrier. CONCLUSION: Significant differences exist between EPs and PCPs in the transition of care process. EPs preferred telephone contact synchronous to the encounter whereas PCPs preferred using the EMR asynchronous to the encounter. Providers believe EP-to-PCP contact is important for improving patient care, but report varied expectations and multiple barriers to effective communication. This study highlights the need to optimize technology for an effective transition of care from the ED to the outpatient setting.

Reduced N-Type Ca2+ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis.

BACKGROUND: Attenuated cardiac vagal activity is associated with ventricular arrhythmogenesis and related mortality in patients with chronic heart failure. Our recent study has shown that expression of N-type Ca2+ channel α-subunits (Cav2.2-α) and N-type Ca2+ currents are reduced in intracardiac ganglion neurons from rats with chronic heart failure. Rat intracardiac ganglia are divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion. Ventricular myocardium receives projection of neuronal terminals only from the AVG. In this study we tested whether a decrease in N-type Ca2+ channels in AVG neurons contributes to ventricular arrhythmogenesis. METHODS AND RESULTS: Lentiviral Cav2.2-α shRNA (2 µL, 2×107 pfu/mL) or scrambled shRNA was in vivo transfected into rat AVG neurons. Nontransfected sham rats served as controls. Using real-time single-cell polymerase chain reaction and reverse-phase protein array, we found that in vivo transfection of Cav2.2-α shRNA decreased expression of Cav2.2-α mRNA and protein in rat AVG neurons. Whole-cell patch-clamp data showed that Cav2.2-α shRNA reduced N-type Ca2+ currents and cell excitability in AVG neurons. The data from telemetry electrocardiographic recording demonstrated that 83% (5 out of 6) of conscious rats with Cav2.2-α shRNA transfection had premature ventricular contractions (P<0.05 versus 0% of nontransfected sham rats or scrambled shRNA-transfected rats). Additionally, an index of susceptibility to ventricular arrhythmias, inducibility of ventricular arrhythmias evoked by programmed electrical stimulation, was higher in rats with Cav2.2-α shRNA transfection compared with nontransfected sham rats and scrambled shRNA-transfected rats. CONCLUSIONS: A decrease in N-type Ca2+ channels in AVG neurons attenuates vagal control of ventricular myocardium, thereby initiating ventricular arrhythmias.