Emergency Medicine Commons^™

Lymphotoxin-Α Is A Novel Adiponectin Expression Suppressor Following Myocardial Ischemia/Reperfusion., Wayne Bond Lau, Yanqing Zhang, Jianli Zhao, Baojiang Liu, Xiaoliang Wang, Yuexing Yuan, Theodore A. Christopher, Bernard Lopez, Erhe Gao, Walter J. Koch, Xin L. Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

Recent clinical observations demonstrate adiponectin (APN), an adipocytokine with potent cardioprotective actions, is significantly reduced following myocardial ischemia/reperfusion (MI/R). However, mechanisms responsible for MI/R-induced hypoadiponectinemia remain incompletely understood. Adult male mice were subjected to 30-min MI followed by varying reperfusion periods. Adipocyte APN mRNA and protein expression and plasma APN and TNFα concentrations were determined. APN expression/production began to decline 3 h after reperfusion (reaching nadir 12 h after reperfusion), returning to control levels 7 days after reperfusion. Plasma TNFα levels began to increase 1 h after reperfusion, peaking at 3 h and returning to control levels 24 h after …

Clinician-Performed Beside Ultrasound For The Diagnosis Of Traumatic Pneumothorax., Bon S. Ku, Jason M. Fields, Brendan Carr, Worth W Everett, Vincent H Gracias, Anthony J Dean

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Prior studies have reported conflicting results regarding the utility of ultrasound in the diagnosis of traumatic pneumothorax (PTX) because they have used sonologists with extensive experience. This study evaluates the characteristics of ultrasound for PTX for a large cohort of trauma and emergency physicians.

METHODS: This was a prospective, observational study on a convenience sample of patients presenting to a trauma center who had a thoracic ultrasound (TUS) evaluation for PTX performed after the Focused Assessment with Sonography for Trauma exam. Sonologists recorded their findings prior to any other diagnostic studies. The results of TUS were compared to one …

Tumor Necrosis Factor-Α And Lymphotoxin-Α Mediate Myocardial Ischemic Injury Via Tnf Receptor 1, But Are Cardioprotective When Activating Tnf Receptor 2., Yanqing Zhang, Jianli Zhao, Wayne Bond Lau, Li-Yuan Jiao, Baojiang Liu, Yuexing Yuan, Xiaoliang Wang, Erhe Gao, Walter J Koch, Xin-Liang Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

OBJECTIVE: This study determines the roles of tumor necrosis factor-α (TNFα) and lymphotoxin-α (LTα) in post-myocardial infarction (post-MI) cardiac injury, and identifies the TNF receptor type responsible for TNFα- and LTα-mediated cardiac injury.

METHODS AND RESULTS: Adult male wild type (WT), TNFα(-/-), LTα(-/-), TNFR1(-/-), and TNFR2(-/-) mice were subjected to MI via coronary artery occlusion. Functional, histological, and biochemical analyses were performed 1 to 7 days post-MI. In WT mice, MI significantly increased both TNFα and LTα levels in plasma, but in distinct temporal manner. Plasma TNFα peaked 1 day after MI, and decreased toward baseline 3 days after MI. …

Aortic Dissection Presenting As Gait Disturbance: A Case Report., Michael Estreicher, Joseph Portale, Bernard Lopez

Department of Emergency Medicine Faculty Papers

Emergency medicine dogma traditionally teaches that aortic dissection presents as tearing chest pain, radiating to the back. This case report describes a 55 year old woman presenting with a left homonymous hemianopsia and resultant gait disturbance. Initial head CT demonstrated a right parietal infarct, and chest radiograph demonstrated a markedly widened mediastinum. Acute Stanford Type A aortic dissection was subsequently confirmed. This report provides further evidence for atypical, painless presentations of aortic dissection. Given recent literature on the increasing prevalence of painless dissection, the disease entity should be included in the differential diagnosis for stroke, and a simple portable chest …

Rewarming For Accidental Hypothermia In An Urban Medical Center Using Extracorporeal Membrane Oxygenation., David Morley, Kentaro Yamane, Rika O'Malley, Nicholas Cavarocchi, Hitoshi Hirose

Department of Emergency Medicine Faculty Papers

BACKGROUND: Accidental hypothermia complicated by cardiac arrest carries a high mortality rate in urban areas. For moderate hypothermia cases conventional rewarming methods are usually adequate, however in severe cases extracorporeal membrane oxygenation (ECMO) is known to provide the most efficient rewarming with complete cardiopulmonary support. We report a case of severe hypothermia complicated by prolonged cardiac arrest successfully resuscitated using ECMO.

CASE REPORT: A 45 year old female was brought to our emergency department with a core body temperature

CONCLUSIONS: This case demonstrates the advantages of advanced internal rewarming techniques, such as ECMO, for quick and efficient rewarming of severely …

Ginsenoside Rd Attenuates Myocardial Ischemia/Reperfusion Injury Via Akt/Gsk-3Β Signaling And Inhibition Of The Mitochondria-Dependent Apoptotic Pathway., Yang Wang, Xu Li, Xiaoliang Wang, Wayne Bond Lau, Yajing Wang, Yuan Xing, Xing Zhang, Xinliang Ma, Feng Gao

Department of Emergency Medicine Faculty Papers

Evidence suggests Ginsenoside Rd (GSRd), a biologically active extract from the medical plant Panax Ginseng, exerts antioxidant effect, decreasing reactive oxygen species (ROS) formation. Current study determined the effect of GSRd on myocardial ischemia/reperfusion (MI/R) injury (a pathological condition where ROS production is significantly increased) and investigated the underlying mechanisms. The current study utilized an in vivo rat model of MI/R injury and an in vitro neonatal rat cardiomyocyte (NRC) model of simulated ischemia/reperfusion (SI/R) injury. Infarct size was measured by Evans blue/TTC double staining. NRC injury was determined by MTT and lactate dehydrogenase (LDH) leakage assay. ROS accumulation and …

Effect Of Iron Chelators On Methemoglobin And Thrombin Preconditioning., Jing Chen-Roetling, Jesse Sinanan, Raymond F. Regan

Department of Emergency Medicine Faculty Papers

Cell loss immediately adjacent to an intracerebral hemorrhage may be mediated in part by the toxicities of extracellular hemoglobin (Hb) and thrombin. However, at low concentrations, these proteins induce tolerance to hemin and iron that may limit further peri-hematomal injury as erythrocyte lysis progresses. The mechanisms mediating these preconditioning effects have not been completely defined, but increased expression of both heme oxygenase (HO)-1 and iron binding proteins likely contributes. In the present study, we hypothesized that iron chelator therapy would attenuate this protective response. Pretreatment of cortical glial cultures (> 90 % GFAP+) with 3 μM methemoglobin (metHb) or 5 …

Decrease In Central Venous Catheter Placement And Complications Due To Utilization Of Ultrasound-Guided Peripheral Intravenous Catheters, Arthur K Au, Masashi Rotte, Robert Grzybowski, Bon Ku, Jason M. Fields

Department of Emergency Medicine Faculty Papers

Poster presented at: American College of Emergency Physicians (ACEP) conference.

Introduction: -Up to 40% of ED visits include diagnostic blood tests and 26% result in administration of IV fluids necessitating successful peripheral intravenous (IV) catheter placement.1 -There is a subset of patients with difficult IV access (DIVA) in which traditional cannulation methods are unsuccessful resulting in central venous cannulation (CVC). -CVCs have a 5-15 percent complication rate2 and attributable costs per CVC related infection have been estimated at $34,508-$56,000.3 -Ultrasound-guided peripheral IV catheters (USGPIVs) provide a method of potentially decreasing the need for CVC placement, however due to poor durability …

The Alternative Crosstalk Between Rage And Nitrative Thioredoxin Inactivation During Diabetic Myocardial Ischemia-Reperfusion Injury., Yi Liu, Yan Qu, Rutao Wang, Yanzhuo Ma, Chenhai Xia, Chao Gao, Jingyi Liu, Kun Lian, Aibing Xu, Xiaoyan Lu, Lu Sun, Lu Yang, Wayne B. Lau, Erhe Gao, Walter Koch, Haichang Wang, Ling Tao

Department of Emergency Medicine Faculty Papers

The receptor for advanced glycation end products (RAGE) and thioredoxin (Trx) play opposing roles in diabetic myocardial ischemia-reperfusion (MI/R) injury. We recently demonstrated nitrative modification of Trx leads to its inactivation and loss of cardioprotection. The present study is to determine the relationship between augmented RAGE expression and diminished Trx activity pertaining to exacerbated MI/R injury in the diabetic heart. The diabetic state was induced in mice by multiple intraperitoneal low-dose streptozotocin injections. RAGE small-interfering RNA (siRNA) or soluble RAGE (sRAGE, a RAGE decoy) was via intramyocardial and intraperitoneal injection before MI/R, respectively. Mice were subjected to 30 min of …

The Effect Of Vessel Depth, Diameter, And Location On Ultrasound-Guided Peripheral Intravenous Catheter Longevity., J Matthew Fields, Anthony J Dean, Raleigh W Todman, Arthur K Au, Kenton L Anderson, Bon S Ku, Jesse M Pines, Nova L Panebianco

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Ultrasound-guided peripheral intravenous catheters (USGPIVs) have been observed to have poor durability. The current study sets out to determine whether vessel characteristics (depth, diameter, and location) predict USGPIV longevity.

METHODS: A secondary analysis was performed on a prospectively gathered database of patients who underwent USGPIV placement in an urban, tertiary care emergency department. All patients in the database had a 20-gauge, 48-mm-long catheter placed under ultrasound guidance. The time and reason for USGPIV removal were extracted by retrospective chart review. A Kaplan-Meier survival analysis was performed.

RESULTS: After 48 hours from USGPIV placement, 32% (48/151) had failed prematurely, 24% …

C1q/Tumor Necrosis Factor-Related Protein-3, A Newly Identified Adipokine, Is A Novel Antiapoptotic, Proangiogenic, And Cardioprotective Molecule In The Ischemic Mouse Heart., Wei Yi, Yang Sun, Yuexing Yuan, Wayne Bond Lau, Qijun Zheng, Xiaoliang Wang, Yajing Wang, Xiying Shang, Erhe Gao, Walter J Koch, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

BACKGROUND: Obesity and diabetes mellitus adversely affect postischemic heart remodeling via incompletely understood mechanisms. C1q/tumor necrosis factor-related protein-3 (CTRP3) is a newly identified adipokine exerting beneficial metabolic regulation, similar to adiponectin. The aim of the present study was to determine whether CTRP3 may regulate postischemic cardiac remodeling and cardiac dysfunction, and, if so, to elucidate the underlying mechanisms.

METHODS AND RESULTS: Male adult mice were subjected to myocardial infarction (MI) via left anterior descending coronary artery occlusion. Both the effect of MI on endogenous CTRP3 expression/production and the effect of exogenous CTRP3 (adenovirus or recombinant CTRP3) replenishment on MI injury …

Essential Role Of Caveolin-3 In Adiponectin Signalsome Formation And Adiponectin Cardioprotection., Yajing Wang, Xiaoliang Wang, Jean-François Jasmin, Wayne Bond Lau, Rong Li, Yuexin Yuan, Wei Yi, Kurt Chuprun, Michael P. Lisanti, Walter J Koch, Erhe Gao, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Adiponectin (APN) system malfunction is causatively related to increased cardiovascular morbidity/mortality in diabetic patients. The aim of the current study was to investigate molecular mechanisms responsible for APN transmembrane signaling and cardioprotection.

METHODS AND RESULTS: Compared with wild-type mice, caveolin-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery; P

CONCLUSIONS: Taken together, these results demonstrated for the first time that Cav-3 plays an essential role in APN transmembrane signaling and APN anti-ischemic/cardioprotective actions.

Physicians' Ability To Predict Hospital Length Of Stay For Patients Admitted To The Hospital From The Emergency Department., Gregory Mak, William D Grant, James C Mckenzie, John B Mccabe

Department of Emergency Medicine Faculty Papers

Accurate predictions of patient length of stay (LOS) in the hospital can effectively manage hospital resources and increase efficiency of patient care. A study was done to assess emergency medicine physicians' ability of predicting the LOS of patients who enter the hospital through the ER. Results indicate that EM physicians are relatively accurate with their pediatric patients than any other age groups. In addition, as actual hospital LOS increases, the prediction accuracy decreases. Possible reasons may be due increasing medical complications associated with increasing age and this may lead to overall longer stays. Other variables such as the admitted service …

Association Of Maximum Weight With Hyperuricemia Risk: A Retrospective Study Of 21,414 Chinese People., Bin Gao, Jie Zhou, Jiapu Ge, Yaping Zhang, Fei Chen, Wayne B Lau, Yi Wan, Nanyan Zhang, Ying Xing, Li Wang, Jianfang Fu, Xiaomiao Li, Hongxia Jia, Xin Zhao, Qiuhe Ji

Department of Emergency Medicine Faculty Papers

BACKGROUND: Obesity has been demonstrated to be associated with increased serum uric acid (SUA); however, little is known regarding the relationship between maximum weight, or maximum weight fluctuation, and uric acid concentration. Through retrospective means, we determined the association of maximum weight with SUA risk.

METHODS: Data of 21,414 participants (8,630 males and 12,784 females) from the 2007-8 China National Diabetes and Metabolic Disorders Study were analyzed for parameters including lifestyle habits, biochemical blood analysis and self-reported maximum weight.

RESULTS: Elevated SUA subjects shared a cluster of demographic features. After adjustment for age, gender, education, smoking, drinking, physical activity, WHR, …

Reduced Cardioprotective Action Of Adiponectin In High-Fat Diet-Induced Type Ii Diabetic Mice And Its Underlying Mechanisms., Wei Yi, Yang Sun, Erhe Gao, Xufeng Wei, Wayne Bond Lau, Qijun Zheng, Yajing Wang, Yuexing Yuan, Xiaoliang Wang, Ling Tao, Rong Li, Walter Koch, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Diabetes exacerbates ischemic heart disease morbidity and mortality via incompletely understood mechanisms. Although adiponectin (APN) reduces myocardial ischemia/reperfusion (MI/R) injury in nondiabetic animals, whether APN's cardioprotective actions are altered in diabetes, a pathologic condition with endogenously reduced APN, has never been investigated. High-fat diet (HD)-induced diabetic mice and normal diet (ND) controls were subjected to MI via coronary artery ligation, and given vehicle or APN globular domain (gAPN, 2 μg/g) 10 min before reperfusion. Compared to ND mice (where gAPN exerted pronounced cardioprotection), HD mice manifested greater MI/R injury, and a tripled gAPN dose was requisite to achieve cardioprotective extent …

Systemic Adiponectin Malfunction As A Risk Factor For Cardiovascular Disease., Wayne Bond Lau, Ling Tao, Yajing Wang, Rong Li, Xin L Ma

Department of Emergency Medicine Faculty Papers

Adiponectin (Ad) is an abundant protein hormone regulatory of numerous metabolic processes. The 30 kDa protein originates from adipose tissue, with full-length and globular domain circulatory forms. A collagenous domain within Ad leads to spontaneous self-assemblage into various oligomeric isoforms, including trimers, hexamers, and high-molecular-weight multimers. Two membrane-spanning receptors for Ad have been identified, with differing concentration distribution in various body tissues. The major intracellular pathway activated by Ad includes phosphorylation of AMP-activated protein kinase, which is responsible for many of Ad's metabolic regulatory, anti-inflammatory, vascular protective, and anti-ischemic properties. Additionally, several AMP-activated protein kinase-independent mechanisms responsible for Ad's anti-inflammatory …

Advanced Glycation End Products Accelerate Ischemia/Reperfusion Injury Through Receptor Of Advanced End Product/Nitrative Thioredoxin Inactivation In Cardiac Microvascular Endothelial Cells., Yi Liu, Yanzhuo Ma, Rutao Wang, Chenhai Xia, Rongqing Zhang, Kun Lian, Ronghua Luan, Lu Sun, Lu Yang, Wayne B Lau, Haichang Wang, Ling Tao

Department of Emergency Medicine Faculty Papers

The advanced glycation end products (AGEs) are associated with increased cardiac endothelial injury. However, no causative link has been established between increased AGEs and enhanced endothelial injury after ischemia/reperfusion. More importantly, the molecular mechanisms by which AGEs may increase endothelial injury remain unknown. Adult rat cardiac microvascular endothelial cells (CMECs) were isolated and incubated with AGE-modified bovine serum albumin (BSA) or BSA. After AGE-BSA or BSA preculture, CMECs were subjected to simulated ischemia (SI)/reperfusion (R). AGE-BSA increased SI/R injury as evidenced by enhanced lactate dehydrogenase release and caspase-3 activity. Moreover, AGE-BSA significantly increased SI/R-induced oxidative/nitrative stress in CMECs (as measured …

Dynamic Alteration Of Adiponectin/Adiponectin Receptor Expression And Its Impact On Myocardial Ischemia/Reperfusion In Type 1 Diabetic Mice., Yanzhuo Ma, Yi Liu, Shaowei Liu, Yan Qu, Rutao Wang, Chenhai Xia, Haifeng Pei, Kun Lian, Tao Yin, Xiaoyan Lu, Lu Sun, Lu Yang, Yanjie Cao, Wayne Bond Lau, Erhe Gao, Haichang Wang, Ling Tao

Department of Emergency Medicine Faculty Papers

The present study determined the dynamic change of adiponectin (APN, a cardioprotective adipokine), its receptor expression, and their impact upon myocardial ischemia/reperfusion (MI/R) injury during type 1 diabetes mellitus (T1DM) progression, and involved underlying mechanisms. Diabetic state was induced in mice via multiple intraperitoneal injections of low-dose streptozotocin. The dynamic change of plasma APN concentration and cardiac APN receptor-1 and -2 (AdipoR1/2) expression were assessed immediately after diabetes onset (0 wk) and 1, 3, 5, and 7 wk thereafter. Indicators of MI/R injury (infarct size, apoptosis, and LDH release) were determined at 0, 1, and 7 wk of DM duration. …

Apotransferrin Protects Cortical Neurons From Hemoglobin Toxicity, Jing Chen-Roetling, Lifen Chen, Raymond F. Regan

Department of Emergency Medicine Faculty Papers

The protective effect of iron chelators in experimental models of intracerebral hemorrhage suggests that nonheme iron may contribute to injury to perihematomal cells. Therapy with high affinity iron chelators is limited by their toxicity, which may be due in part to sequestration of metals in an inaccessible complex. Transferrin is unique in chelating iron with very high affinity while delivering it to cells as needed via receptor-mediated endocytosis. However, its efficacy against iron-mediated neuronal injury has never been described, and was therefore evaluated in this study using an established cell culture model of hemoglobin neurotoxicity. At concentrations similar to that …

Methylglyoxal Increases Cardiomyocyte Ischemia-Reperfusion Injury Via Glycative Inhibition Of Thioredoxin Activity., Xiaoliang Wang, Wayne B. Lau, Yue-Xing Yuan, Ya-Jing Wang, Wei Yi, Theodore A. Christopher, Bernard L. Lopez, Hui-Rong Liu, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Diabetes mellitus (DM) is closely related to cardiovascular morbidity and mortality, but the specific molecular basis linking DM with increased vulnerability to cardiovascular injury remains incompletely understood. Methylglyoxal (MG), a precursor to advanced glycation end products (AGEs), is increased in diabetic patient plasma, but its role in diabetic cardiovascular complications is unclear. Thioredoxin (Trx), a cytoprotective molecule with antiapoptotic function, has been demonstrated to be vulnerable to glycative inhibition, but whether Trx is glycatively inhibited by MG, thus contributing to increased cardiac injury, has never been investigated. Cultured H9c2 cardiomyocytes were treated with MG (200 muM) for 6 days. The …

Cardiomyocyte-Derived Adiponectin Is Biologically Active In Protecting Against Myocardial Ischemia-Reperfusion Injury., Yajing Wang, Wayne Bond Lau, Erhe Gao, Ling Tao, Yuexing Yuan, Rong Li, Xiaoliang Wang, Walter J. Koch, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Adiponectin (APN) has traditionally been viewed as an adipocyte-specific endocrine molecule with cardioprotective effects. Recent studies suggest that APN is also expressed in cardiomyocytes. However, biological significances of this locally produced APN remain completely unknown. The aim of this study was to investigate the pathological and pharmacological significance of cardiac-derived APN in cardiomyocyte pathology. Adult cardiomyocytes from wild-type littermates (WT) or gene-deficient mice were pretreated with vehicle (V) or rosiglitazone (RSG) for 6 h followed by simulated ischemia-reperfusion (SI/R, 3 h/12 h). Compared with WT cardiomyocytes, myocytes from APN knockout (APN-KO) mice sustained greater SI/R injury, evidenced by greater oxidative/nitrative …

Cardioprotective Effect Of Adiponectin Is Partially Mediated By Its Ampk-Independent Antinitrative Action., Yajing Wang, Ling Tao, Yuexing Yuan, Wayne Bond Lau, Rong Li, Bernard L. Lopez, Theodore A. Christopher, Rong Tian, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Adiponectin (APN) exerts its metabolic regulation largely through AMP-dependent protein kinase (AMPK). However, the role of AMPK in APN's antiapoptotic effect in ischemic-reperfused (I/R) adult cardiomyocytes remains incompletely understood. The present study was designed to determine the involvement of AMPK in the antiapoptotic signaling of APN. Cardiomyocytes from adult male mice overexpressing a dominant-negative alpha(2)-subunit of AMPK (AMPK-DN) or wild-type (WT) littermates were subjected to simulated I/R (SI/R) and pretreated with 2 microg/ml globular domain of APN (gAPN) or vehicle. SI/R-induced cardiomyocyte apoptosis was modestly increased in AMPK-DN cardiomyocytes (P < 0.05). Treatment with gAPN significantly reduced SI/R-induced apoptosis in WT cardiomyocytes as well as in AMPK-DN cardiomyocytes, indicating that the antiapoptotic effect of gAPN is partially AMPK independent. Furthermore, gAPN-induced endothelial nitric oxide synthase (eNOS) phosphorylation was significantly reduced in AMPK-DN cardiomyocytes, suggesting that the APN-eNOS signaling axis is impaired in AMPK-DN cardiomyocytes. Additional experiments demonstrated that treatment of AMPK-DN cardiomyocytes with gAPN reduced SI/R-induced NADPH oxidase overexpression, decreased superoxide generation, and blocked peroxynitrite formation to the same extent as that observed in WT cardiomyocytes. Collectively, our present study demonstrated that although the metabolic and eNOS activation effect of APN is largely mediated by AMPK, the superoxide-suppressing effect of APN is not mediated by AMPK, and this AMPK-independent antioxidant property of APN increased nitric oxide bioavailability and exerted significant antiapoptotic effect.

Identifying Inaccuracies On Emergency Medicine Residency Applications., Eric D Katz, Lee Shockley, Lawrence Kass, David Howes, Janis P Tupesis, Christopher Weaver, Osman R Sayan, Victoria Hogan, Jason Begue, Diamond Vrocher, Jackie Frazer, Timothy Evans, Gene Hern, Ralph Riviello, Antonio Rivera, Keith Kinoshita, Edward Ferguson

Department of Emergency Medicine Faculty Papers

BACKGROUND: Previous trials have showed a 10-30% rate of inaccuracies on applications to individual residency programs. No studies have attempted to corroborate this on a national level. Attempts by residency programs to diminish the frequency of inaccuracies on applications have not been reported. We seek to clarify the national incidence of inaccuracies on applications to emergency medicine residency programs. METHODS: This is a multi-center, single-blinded, randomized, cohort study of all applicants from LCME accredited schools to involved EM residency programs. Applications were randomly selected to investigate claims of AOA election, advanced degrees and publications. Errors were reported to applicants' deans …