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- Double Sequential External Defibrillation in Out-of-Hospital Refractory Ventricular Fibrillation: A Report of Ten Cases. [JOURNAL ARTICLE]
- Prehosp Emerg Care 2014 Sep 22.
Abstract Background. Ventricular fibrillation (VF) is considered the out-of-hospital cardiac arrest (OOHCA) rhythm with the highest likelihood of neurologically intact survival. Unfortunately, there are occasions when VF does not respond to standard defibrillatory shocks. Current American Heart Association (AHA) guidelines acknowledge that the data are insufficient in determining the optimal pad placement, waveform, or energy level that produce the best conversion rates from OOHCA with VF. Objective. To describe a technique of double sequential external defibrillation (DSED) for cases of refractory VF (RVF) during OOHCA resuscitation. Methods. A retrospective case series was performed in an urban/suburban emergency medical services (EMS) system with advanced life support care and a population of 900,000. Included were all adult OOHCAs having RVF during resuscitation efforts by EMS providers. RVF was defined as persistent VF following at least 5 unsuccessful single shocks, epinephrine administration, and a dose of antiarrhythmic medication. Once the patient was in RVF, EMS personnel applied a second set of pads and utilized a second defibrillator for single defibrillation with the new monitor/pad placement. If VF continued, EMS personnel then utilized the original and second monitor/defibrillator charged to maximum energy, and shocks were delivered from both machines simultaneously. Data were collected from electronic dispatch and patient care reports for descriptive analysis. Results. From 01/07/2008 to 12/31/2010, a total of 10 patients were treated with DSED. The median age was 76.5 (IQR: 65-82), with median resuscitation time of 51minutes (IQR: 45-62). The median number of single shocks was 6.5 (IQR: 6-11), with a median of 2 (IQR: 1-3) DSED shocks delivered. VF broke after DSED in 7 cases (70%). Only 3 patients (30%) had ROSC in the field, and none survived to discharge. Conclusion. This case series demonstrates that DSED may be a feasible technique as part of an aggressive treatment plan for RVF in the out-of-hospital setting. In this series, RVF was terminated 70% of the time, but no patient survived to discharge. Further research is needed to better understand the characteristics of and treatment strategies for RVF.
- Epinephrine Enhances the Response of Macrophages under LPS Stimulation. [JOURNAL ARTICLE]
- Biomed Res Int 2014.:254686.
Trauma associated with infection may directly trigger a neuroendocrine reaction in vivo while the hormone epinephrine is known to mediate immune responses to inflammation after injury. However, the role of epinephrine during the earliest stage of trauma still remains unclear. We therefore explored the role of epinephrine on activated macrophages under LPS stimulation in vitro as well as the mechanisms underlying its effect. Dose- and time-dependent effects of epinephrine on macrophage immune function were assessed after LPS activation. We also employed CD14 siRNA interference to investigate whether CD14 played a role in the mechanism underlying the effect of epinephrine on LPS-induced macrophage responses. Our results showed that epinephrine pretreatment (10 ng/mL) significantly promoted immune responses from LPS stimulated macrophages, including phagocytic rate, phagocytic index, TNFα/IL-1β/IL-10 secretion, and CD14 expression (P < 0.05). Moreover, TNFα/IL-1β/IL-10 levels attained their peak value 1 hour after incubation with 10 ng/mL epinephrine (P < 0.05), and CD14 siRNA transfection dramatically decreased phagocytosis and cytokine secretion by LPS-activated macrophages (P < 0.05). We therefore conclude that 10 ng/mL epinephrine enhances immune responses from macrophages under LPS stimulation and that the underlying mechanism may relate to CD14 upregulation on the surface of macrophages.
- Better detection of platelet aggregation in patients with metabolic syndrome using epinephrine and ADP. [Journal Article]
- Diabetol Metab Syndr 2014; 6(1):93.
Patients with metabolic syndrome (MS) often have increased platelet aggregation. In order to determine which concentration detects a higher level of platelet aggregation in patients with MS, the agonists ADP and epinephrine were compared.The study included 56 subjects with MS and 53 healthy subjects. Blood pressure, weight, body-mass index, and hip-to-waist ratio were collected from all subjects. Insulin, glucose, total serum cholesterol, HDL-C, LDL-C, total triglycerides, markers of plasma atherogenicity, and indices of insulin resistance were measured in all participants. For aggregometry assays, the Born method was used. Platelets were treated with ADP and epinephrine in decreasing concentrations of 2.34, 1.17, and 0.58 μM, as well as, 11.0, 1.1, and 0.55 μM, respectively. ROC curves were plotted to define the diagnostic efficiency of epinephrine levels for MS.Among healthy individuals and MS patients significant differences were observed in body weight, body-mass index, waist-circumference, levels of insulin, indices of insulin resistance, and levels of HDL-cholesterol, LDL-cholesterol and total triglycerides. There was a significant difference in the detection of increased platelet aggregation using 11.0 μM and 0.55 μM epinephrine and 0.58 μM ADP. With both agonists, ROC analysis showed an area under the curve of >0.8 for 11.0 μM epinephrine and 2.34 μM ADP. However, for MS patients, 11.0 μM epinephrine had a slightly better diagnostic efficiency than 2.34 μM ADP.It was found that 11.0 μM epinephrine and 2.34 μM ADP detected better platelet aggregation in patients with MS than in healthy subject. Both concentrations detected increased platelet aggregation in patients with MS.
- Assessment of Platelet Function Analyzer (PFA-100) in Kidney Transplant Patients Before Renal Allograft Biopsy: A Retrospective Single-Center Analysis. [Journal Article]
- Transplant Proc 2014 Sep; 46(7):2259-62.
Kidney biopsy (KB) represents the criterion standard to obtain information on diagnosis and prognosis of renal allograft dysfunctions. However, it can be associated with bleeding complications (BCs). Bleeding time test (BTT), the best predictive indicator of post-biopsy BCs, is not a very reproducible test and is invasive. Therefore, the aim of this study was to evaluate whether the platelet function analyzer (PFA-100), a very reliable test to investigate primary hemostasis, could be useful in predicting the risk of bleeding complications in transplant patients undergoing KB.We carried out a retrospective analysis of PFA-100 collagen-epinephrine (C-EPI) and collagen-adenosine diphosphate (C-ADP) closure times in 119 patients undergoing KB in our center. Data regarding BTT, age, sex, blood pressure, number of renal allograft punctures for each biopsy procedure, thromboplastin time, prothrombin time, complete blood count, and prophylactic therapy with desmopressin were also collected. Major (need for blood transfusion) or minor (no need for any intervention) BCs (hematoma and hematuria) were recorded.Indications for KB were: delayed graft function (n = 23), allograft dysfunction (n = 40), proteinuria (n = 27), allograft dysfunction plus proteinuria (n = 19), and protocol biopsy (n = 10). Nine of the 119 patients (7.5%) developed minor BCs (6 macrohematuria, 3 hematoma), major BCs did not develop. No significant differences were found in any of the clinical and laboratory data, including BTT and PFA-100 (C-EPI and C-ADP) between patients who developed BCs compared with those who did not. In addition, there was no correlation between PFA-100 test (C-EPI and C-ADP) values and BTT data [R(2) = 0.002; P = .6].The PFA-100 test was not useful in predicting the risk of BCs in kidney transplant patients undergoing renal allograft biopsy.
- Efects Of Conventional And Hydrogen Sulfide-Releasing Nonsteroidal Anti-Inflammatory Drugs In Rats With Stress-Induced And Epinephrine-Induced Gastric Damage. [JOURNAL ARTICLE]
- Stress 2014 Sep 19.:1-28.
Abstract Mechanisms of gastric defence under conditions of combined influence of acute stress and nonsteroidal anti-inflammatory drugs (NSAIDs) are still poorly studied. The aim of this study was to explore the effects of different types of NSAIDs (naproxen, celecoxib, and ATB-346) in producing experimental gastric lesions (induced by water restraint stress (WRS) or by epinephrine injection) and to determine the role of lipid peroxidation and the nitric oxide (NO) system in the pathogenesis of the damage. Male rats were used (8 per group). The NSAIDs were all administered at a dose 10 mg·kg(-1) 30 min prior to WRS or epinephrine injection. Administration of naproxen to the control rats caused development of gastric lesions, whereas administration of a hydrogen sulfide (H2S)-releasing NSAID (ATB-346) or a selective cyclooxygenase-2 inhibitor (celecoxib) did not cause gastric damage. In contrast, lipid peroxidation processes were enhanced in all groups as was the activity of nitric oxide (NO) synthase (NOS). Pretreatment with naproxen in the WRS model caused an increase in severity of damage and a decrease in NOS activity. ATB-346 displayed beneficial effects, manifested by a decrease of the area of gastric damage, but parameters of lipid peroxidation and the NOS system did not differ substantially from those in the group treated with naproxen. Administration of different NSAIDs under conditions of epinephrine-induced gastric damage resulted in the decrease of NOS activity and lipid peroxidation. None of the tested NSAIDs exacerbated epinephrine-induced gastric mucosal injury; indeed, they all reduced the extent of damage.
- The Structural Basis of Action of Vanadyl (VO(2+)) Chelates in Cells. [JOURNAL ARTICLE]
- Coord Chem Rev 2014 Nov 1.:1-22.
Much emphasis has been given to vanadium compounds as potential therapeutic reagents for the treatment of diabetes mellitus. Thus far, no vanadium compound has proven efficacious for long-term treatment of this disease in humans. Therefore, in review of the research literature, our goal has been to identify properties of vanadium compounds that are likely to favor physiological and biochemical compatibility for further development as therapeutic reagents. We have, therefore, limited our review to those vanadium compounds that have been used in both in vivo experiments with small, laboratory animals and in in vitro studies with primary or cultured cell systems and for which pharmacokinetic and pharmacodynamics results have been reported, including vanadium tissue content, vanadium and ligand lifetime in the bloodstream, structure in solution, and interaction with serum transport proteins. Only vanadyl (VO(2+)) chelates fulfill these requirements despite the large variety of vanadium compounds of different oxidation states, ligand structure, and coordination geometry synthesized as potential therapeutic agents. Extensive review of research results obtained with use of organic VO(2+)-chelates shows that the vanadyl chelate bis(acetylacetonato)oxidovanadium(IV) [hereafter abbreviated as VO(acac)2], exhibits the greatest capacity to enhance insulin receptor kinase activity in cells compared to other organic VO(2+)-chelates, is associated with a dose-dependent capacity to lower plasma glucose in diabetic laboratory animals, and exhibits a sufficiently long lifetime in the blood stream to allow correlation of its dose-dependent action with blood vanadium content. The properties underlying this behavior appear to be its high stability and capacity to remain intact upon binding to serum albumin. We relate the capacity to remain intact upon binding to serum albumin to the requirement to undergo transcytosis through the vascular endothelium to gain access to target tissues in the extravascular space. Serum albumin, as the most abundant transport protein in the blood stream, serves commonly as the carrier protein for small molecules, and transcytosis of albumin through capillary endothelium is regulated by a Src protein tyrosine kinase system. In this respect it is of interest to note that inorganic VO(2+) has the capacity to enhance insulin receptor kinase activity of intact 3T3-L1 adipocytes in the presence of albumin, albeit weak; however, in the presence of transferrin no activation is observed. In addition to facilitating glucose uptake, the capacity of VO(2+)- chelates for insulin-like, antilipolytic action in primary adipocytes has also been reviewed. We conclude that measurement of inhibition of release of only free fatty acids from adipocytes stimulated by epinephrine is not a sufficient basis to ascribe the observations to purely insulin-mimetic, antilipolytic action. Adipocytes are known to contain both phosphodiesterase-3 and phosphodiesterase-4 (PDE3 and PDE4) isozymes, of which insulin antagonizes lipolysis only through PDE3B. It is not known whether the other isozyme in adipocytes is influenced directly by VO(2+)- chelates. In efforts to promote improved development of VO(2+)- chelates for therapeutic purposes, we propose synergism of a reagent with insulin as a criterion for evaluating physiological and biochemical specificity of action. We highlight two organic compounds that exhibit synergism with insulin in cellular assays. Interestingly, the only VO(2+)- chelate for which this property has been demonstrated, thus far, is VO(acac)2.
- Errors of epinephrine administration during severe allergic-like contrast reactions: lessons learned from a bi-institutional study using high-fidelity simulation testing. [Journal Article]
- Abdom Imaging 2014 Oct; 39(5):1127-33.
To determine the most common errors of epinephrine administration during severe allergic-like contrast reaction management using high-fidelity simulation surrogates.IRB approval and informed consent were obtained for this HIPAA-compliant bi-institutional prospective study of 40 radiology residents, fellows, and faculty who were asked to manage a structured high-fidelity severe allergic-like contrast reaction scenario (i.e., mild hives progressing to mild bronchospasm, then bronchospasm unresponsive to bronchodilators, and finally anaphylactic shock) on an interactive manikin. Intravenous (IV) and intramuscular epinephrine ampules were available to all participants, and the manikin had a functioning intravenous catheter for all scenarios. Video recordings of their performance were reviewed by experts in contrast reaction management, and errors in epinephrine administration were recorded and characterized.No participant (0/40) failed to give indicated epinephrine, but more than half (58% [23/40]) committed an error while doing so. The most common mistake was to administer epinephrine as the first-line treatment for mild bronchospasm (33% [13/40]). Other common errors were to administer IV epinephrine without a subsequent IV saline flush or concomitant IV fluids (25% [10/40]), administer an overdose of epinephrine (8% [3/40]), and administer epinephrine 1:1000 intravenously (8% [3/40]).Epinephrine administration errors are common. Many radiologists fail to administer albuterol as the first-line treatment for mild bronchospasm and fail to flush the IV catheter when administering IV epinephrine. High-fidelity contrast reaction scenarios can be used to identify areas for training improvement.
- Congenital long QT syndrome: Severe Torsades de pointes provoked by epinephrine in a digenic mutation carrier. [JOURNAL ARTICLE]
- Heart Lung 2014 Sep 15.
Congenital Long QT Syndrome (LQTS) is a potentially lethal cardiac channelopathy characterized by prolongation of the corrected QT (QTc) interval on the surface electrocardiogram. The hallmark phenotypic features are syncope, seizure or sudden death, however most of the mutation carriers are asymptomatic and their risk for arrhythmias such as Torsade de pointes (TdP) are low. We report a case of Long QT syndrome with a corrected QT of 520 ms. For symptom - arrhythmia correlation a loop recorder was implanted with no documented arrhythmias. Epinephrine testing was performed for clinical risk stratification leading to Torsades de pointes during recovery phase which required defibrillation. Genetic testing discovered two pathogenic heterozygous mutations in two different LQT genes (SCN5A and KCNQ1). We propose a calcium homeostasis mechanism for the interaction of both mutations that exaggerated the phenotype, while each mutation by itself is causing a relatively modest phenotype.
- Myocardial drug distribution generated from local epicardial application: Potential impact of cardiac capillary perfusion in a swine model using epinephrine. [JOURNAL ARTICLE]
- J Control Release 2014 Sep 16.
Prior studies in small mammals have shown that local epicardial application of inotropic compounds drives myocardial contractility without systemic side effects. Myocardial capillary blood flow, however, may be more significant in larger species than in small animals. We hypothesized that bulk perfusion in capillary beds of the large mammalian heart not only enhances drug distribution after local release, but also clears more drug from the tissue target than in small animals. Epicardial (EC) drug releasing systems were used to apply epinephrine to the anterior surface of the left heart of swine in either point-sourced or distributed configurations. Following local application or intravenous (IV) infusion at the same dose rates, hemodynamic responses, epinephrine levels in the coronary sinus and systemic circulation, and drug deposition across the ventricular wall, around the circumference and down the axis, were measured. EC delivery via point-source release generated transmural epinephrine gradients directly beneath the site of application extending into the middle third of the myocardial thickness. Gradients in drug deposition were also observed down the length of the heart and around the circumference toward the lateral wall, but not the interventricular septum. These gradients extended further than might be predicted from simple diffusion. The circumferential distribution following local epinephrine delivery from a distributed source to the entire anterior wall drove drug toward the inferior wall, further than with point-source release, but again, not to the septum. This augmented drug distribution away from the release source, down the axis of the left ventricle, and selectively toward the left heart follows the direction of capillary perfusion away from the anterior descending and circumflex arteries, suggesting a role for the coronary circulation in determining local drug deposition and clearance. The dominant role of the coronary vasculature is further suggested by the elevated drug levels in the coronary sinus effluent. Indeed, plasma levels, hemodynamic responses, and myocardial deposition remote from the point of release were similar following local EC or IV delivery. Therefore, the coronary vasculature shapes the pharmacokinetics of local myocardial delivery of small catecholamine drugs in large animal models. Optimal design of epicardial drug delivery systems must consider the underlying bulk capillary perfusion currents within the tissue to deliver drug to tissue targets and may favor therapeutic molecules with better potential retention in myocardial tissue.