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OBJECTIVE: To determine the association between high flow supplementary oxygen and 30 day mortality in patients presenting with a suspected acute coronary syndrome (ACS). DESIGN: Pragmatic, cluster randomised, crossover trial. SETTING: Four geographical regions in New Zealand. PARTICIPANTS: 40 872 patients with suspected or confirmed ACS included in the All New Zealand Acute Coronary Syndrome Quality Improvement registry or ambulance ACS pathway during the study periods. 20 304 patients were managed using the high oxygen protocol and 20 568 were managed using the low oxygen protocol. Final diagnosis of ST elevation myocardial infarction (STEMI) and non-STEMI were determined from the registry and ICD-10 discharge codes. INTERVENTIONS: The four geographical regions were randomly allocated to each of two oxygen protocols in six month blocks over two years. The high oxygen protocol recommended oxygen at 6-8 L/min by face mask for ischaemic symptoms or electrocardiographic changes, irrespective of the transcapillary oxygen saturation (SpO2). The low oxygen protocol recommended oxygen only if SpO2 was less than 90%, with a target SpO2 of less than 95%. MAIN OUTCOME MEASURE: 30 day all cause mortality determined from linkage to administrative data. RESULTS: Personal and clinical characteristics of patients managed under both oxygen protocols were well matched. For patients with suspected ACS, 30 day mortality for the high and low oxygen groups was 613 (3.0%) and 642 (3.1%), respectively (odds ratio 0.97, 95% confidence interval 0.86 to 1.08). For 4159 (10%) patients with STEMI, 30 day mortality for the high and low oxygen groups was 8.8% (n=178) and 10.6% (n=225), respectively (0.81, 0.66 to 1.00) and for 10 218 (25%) patients with non-STEMI was 3.6% (n=187) and 3.5% (n=176), respectively (1.05, 0.85 to 1.29). CONCLUSION: In a large patient cohort presenting with suspected ACS, high flow oxygen was not associated with an increase or decrease in 30 day mortality. TRIAL REGISTRATION: ANZ Clinical Trials ACTRN12616000461493.
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Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Oxigenoterapia , Síndrome Coronariana Aguda/diagnóstico , Idoso , Protocolos Clínicos , Análise por Conglomerados , Estudos Cross-Over , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Taxa de SobrevidaRESUMO
The coronavirus 2019 (COVID-19) pandemic requires significant changes to standard operating procedures for non-COVID-19 related illnesses. Balancing the benefit from standard evidence-based treatments with the risks posed by COVID-19 to patients, healthcare workers and to the population at large is difficult due to incomplete and rapidly changing information. In this article, we use management of acute coronary syndromes as a case study to show how these competing risks and benefits can be resolved, albeit incompletely. While the risks due to COVID-19 in patients with acute coronary syndromes is unclear, the benefits of standard management are well established in this condition. As an aid to decision making, we recommend systematic estimation of the risks and benefits for management of any condition where there is likely to be an increase in non-COVID-19 related mortality and morbidity due to changes in routine care.
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Síndrome Coronariana Aguda/terapia , Infecções por Coronavirus/epidemiologia , Gerenciamento Clínico , Intervenção Coronária Percutânea , Pneumonia Viral/epidemiologia , COVID-19 , Tomada de Decisões , Humanos , Nova Zelândia/epidemiologia , Pandemias , Resultado do TratamentoRESUMO
BACKGROUND: Countries with a high incidence of coronavirus 2019 (COVID-19) reported reduced hospitalisations for acute coronary syndromes (ACS) during the pandemic. This study describes the impact of a nationwide lockdown on ACS hospitalisations in New Zealand (NZ), a country with a low incidence of COVID-19. METHODS: All patients admitted to a NZ Hospital with ACS who underwent coronary angiography in the All NZ ACS Quality Improvement registry during the lockdown (23 March - 26 April 2020) were compared with equivalent weeks in 2015-2019. Ambulance attendances and regional community troponin-I testing were compared for lockdown and non-lockdown (1 July 2019 to 16 February 2020) periods. FINDINGS: Hospitalisation for ACS was lower during the 5-week lockdown (105 vs. 146 per-week, rate ratio 0â¢72 [95% CI 0â¢61-0â¢83], p = 0.003). This was explained by fewer admissions for non-ST-segment elevation ACS (NSTE-ACS; p = 0â¢002) but not ST-segment elevation myocardial infarction (STEMI; p = 0â¢31). Patient characteristics and in-hospital mortality were similar. For STEMI, door-to-balloon times were similar (70 vs. 72 min, p = 0â¢52). For NSTE-ACS, there was an increase in percutaneous revascularisation (59% vs. 49%, p<0â¢001) and reduction in surgical revascularisation (9% vs. 15%, p = 0â¢005). There were fewer ambulance attendances for cardiac arrests (98 vs. 110 per-week, p = 0â¢04) but no difference for suspected ACS (408 vs. 420 per-week, p = 0â¢44). Community troponin testing was lower throughout the lockdown (182 vs. 394 per-week, p<0â¢001). INTERPRETATION: Despite the low incidence of COVID-19, there was a nationwide decrease in ACS hospitalisations during the lockdown. These findings have important implications for future pandemic planning. FUNDING: The ANZACS-QI registry receives funding from the New Zealand Ministry of Health.
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Carbon monoxide (CO) is well known as a highly toxic poison at high concentrations, yet in physiologic amounts it is an endogenous biological messenger in organs such as the internal ear and brain. In this study we tested the hypothesis that chronic very mild CO exposure at concentrations 25-ppm increases the expression of oxidative stress protecting enzymes within the cellular milieu of the developing inner ear (cochlea) of the normal CD-1 mouse. In addition we tested also the hypothesis that CO can decrease the pre-existing condition of oxidative stress in the mouse model for the human medical condition systemic lupus erythematosus by increasing two protective enzymes heme-oxygenase-1 (HO-1), and superoxide dismutase-2 (SOD-2). CD-1 and MRL/lpr mice were exposed to mild CO concentrations (25 ppm in air) from prenatal only and prenatal followed by early postnatal day 5 to postnatal day 20. The expression of cell markers specific for oxidative stress, and related neural/endothelial markers were investigated at the level of the gene products by immunohistochemistry, proteomics and mRNA expression (quantitative real time-PCR). We found that in the CD-1 and MRL/lpr mouse cochlea SOD-2 and HO-1 were upregulated. In this mouse model of autoimmune disease defense mechanism are attenuated, thus mild CO exposure is beneficial. Several genes (mRNA) and proteins detected by proteomics involved in cellular protection were upregulated in the CO exposed CD-1 mouse and the MRL/lpr mouse.
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Monóxido de Carbono/administração & dosagem , Cóclea/efeitos dos fármacos , Cóclea/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Cóclea/crescimento & desenvolvimento , Feminino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , GravidezRESUMO
PURPOSE: To assess the face and content validity of a novel, full physics, full procedural, virtual reality simulation housed in a hybrid procedure suite. METHODS AND MATERIALS: After completing 60 minutes of hands-on training in uterine artery embolization and coronary angioplasty, 24 radiologists and 18 cardiologists with mean 10 years of endovascular experience assessed the functionality of a comprehensive hybrid procedure suite simulation (Orcamp; Orzone, Gothenburg, Sweden). RESULTS: C-arm and operating table functionality and realism were reliably (α = 0.0.89-0.92) rated highly (80/100). Performance realism of the catheter, guide wire, fluoroscopy image, electrocardiogram, and vital signs readout also reliably and statistically significantly predicted subjects' overall positive assessment (mean = 87/100) of the simulation experience in a multiple regression model (α = .83; r = 0.85 and r(2) = 0.67; P < .0001). CONCLUSIONS: This study reports a quantitative evaluation of a comprehensive simulation of an authentic procedure suite for image-guided intravascular procedures. This new facility affords the opportunity for trainers to provide higher fidelity training of operative technical, procedural, and management skills in the realistic context of a complete procedure suite with all its complexities and potential distractions.
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Angioplastia/educação , Simulação por Computador , Instrução por Computador , Educação de Pós-Graduação em Medicina/métodos , Embolização da Artéria Uterina/educação , Adulto , Angioplastia/instrumentação , Cateterismo Cardíaco , Cateterismo Periférico , Competência Clínica , Instrução por Computador/instrumentação , Eletrocardiografia , Desenho de Equipamento , Feminino , Fluoroscopia , Humanos , Pessoa de Meia-Idade , Radiografia Intervencionista , Análise e Desempenho de Tarefas , Embolização da Artéria Uterina/instrumentaçãoAssuntos
Angioplastia Coronária com Balão , Hemorragia/tratamento farmacológico , Hirudinas/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Piperazinas/administração & dosagem , Stents , Tiofenos/administração & dosagem , Trombose/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão/efeitos adversos , Estudos de Coortes , Quimioterapia Combinada , Feminino , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Cloridrato de Prasugrel , Proteínas Recombinantes/administração & dosagem , Stents/efeitos adversos , Trombose/epidemiologia , Trombose/etiologia , Fatores de TempoRESUMO
The expression of neuroglobin (Ngb) and cytoglobin (Cygb), two recently discovered globins with a potential neuroprotective activity against hypoxia and oxidative stress, was investigated in the cerebellum of young rats (postnatal day 20) after being exposed to chronic mild carbon monoxide (CO) at 25 ppm during prenatal (group A), prenatal and postnatal (group B), the postnatal period only (group C), and air (group D). The expression of genes associated with hypoxia signaling pathways was also investigated in the rat cerebella by real-time RT-PCR after CO exposure. Ngb and Cygb mRNAs did not change in any CO-exposed group. Quantitative immunohistochemistry showed no significant change in Ngb protein; however, there was a significant increase of Cygb protein in rats from groups A, B, and C when compared with group D. In group B, genes related to the generation of reactive oxygen species (Nos2) and lipid metabolism (Apat2) were upregulated. In contrast, no changes were found in the expression of 8 genes typically upregulated by hypoxic conditions (Angptl4, Arnt2, Casp1, Crebbp, Hif1a, Hif3a, Mt3, or Vegfa) in any CO-exposed group, suggesting that hypoxia-related gene expression is not altered by this mild CO exposure. Cygb but not Ngb may protect cerebellar cells from the chronic presence of CO exposure during prenatal and postnatal development.
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Monóxido de Carbono/toxicidade , Hipóxia Celular/genética , Cerebelo/metabolismo , Regulação da Expressão Gênica , Globinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Efeitos Tardios da Exposição Pré-Natal , Envelhecimento , Animais , Cerebelo/crescimento & desenvolvimento , Citoglobina , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Globinas/genética , Proteínas do Tecido Nervoso/genética , Neuroglobina , Gravidez , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transcrição GênicaRESUMO
The distribution of neuroglobin (Ngb) was investigated in the normal rat cochlea using immunohistochemistry and non-radioactive insitu hybridization. We also determined whether chronic, very mild CO exposure at 25ppm in air over the gestational and postnatal period alters the expression of Ngb. Pregnant rats were exposed chronically to CO from gestational days 5-20. Four groups were made as follows: prenatal exposure to CO only; prenatal exposure to CO followed by postnatal exposure from postnatal days (5) P5 to P20; rat pups were exposed to CO from P5 to P20; controls (air without CO). In normal adult rats and control group pups, Ngb was found in spiral ganglia neurons, fibrocytes of the spiral ligament, and supporting cells of the organ of Corti. Ngb was not present in the stria vascularis and the inner and outer hair cells. At P20 Ngb immunoreactivity and transcript expression decreased in spiral ganglia neurons and the spiral ligament in the prenatal and pre- and postnatal groups. This decrease was not observed in the postnatal group. Ngb-IR did not decrease in supporting cells in any CO group. Cytochrome-C immunoreactivity followed Ngb distribution in normal controls and CO treated groups. A decrease in Ngb in spiral ganglia neurons and rat spiral ligament, but not in supporting cells, following CO exposure supports the idea that chronic, mild exposure to CO may create a vulnerable cellular environment predisposed to adverse cochlear development.
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Monóxido de Carbono/efeitos adversos , Cóclea/crescimento & desenvolvimento , Cóclea/metabolismo , Globinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Cóclea/citologia , Citocromos c/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Globinas/genética , Humanos , Masculino , Camundongos , Proteínas do Tecido Nervoso/genética , Neuroglobina , Neurônios/metabolismo , Gravidez , RNA Mensageiro/metabolismo , Ratos , Gânglio Espiral da Cóclea/citologiaRESUMO
BACKGROUND: The present study was designed to test the hypothesis that chronic very mild prenatal carbon monoxide (CO) exposure (25 parts per million) subverts the normal development of the rat cerebellar cortex. Studies at this chronic low CO exposure over the earliest periods of mammalian development have not been performed to date. Pregnant rats were exposed chronically to CO from gestational day E5 to E20. In the postnatal period, rat pups were grouped as follows: Group A: prenatal exposure to CO only; group B: prenatal exposure to CO then exposed to CO from postnatal day 5 (P5) to P20; group C: postnatal exposure only, from P5 to P20, and group D, controls (air without CO). At P20, immunocytochemical analyses of oxidative stress markers, and structural and functional proteins were assessed in the cerebellar cortex of the four groups. Quantitative real time PCR assays were performed for inducible (iNOS), neuronal (nNOS), and endothelial (eNOS) nitric oxide synthases. RESULTS: Superoxide dismutase-1 (SOD1), SOD2, and hemeoxygenase-1 (HO-1) immunoreactivity increased in cells of the cerebellar cortex of CO-exposed pups. INOS and nitrotyrosine immunoreactivity also increased in blood vessels and Purkinje cells (PCs) of pups from group-A, B and C. By contrast, nNOS immunoreactivity decreased in PCs from group-B. Endothelial NOS immunoreactivity showed no changes in any CO-exposed group. The mRNA levels for iNOS were significantly up-regulated in the cerebellum of rats from group B; however, mRNA levels for nNOS and eNOS remained relatively unchanged in groups A, B and C. Ferritin-H immunoreactivity increased in group-B. Immunocytochemistry for neurofilaments (structural protein), synapsin-1 (functional protein), and glutamic acid decarboxylase (the enzyme responsible for the synthesis of the inhibitory neurotransmitter GABA), were decreased in groups A and B. Immunoreactivity for two calcium binding proteins, parvalbumin and calbindin, remained unchanged. The immunoreactivity of the astrocytic marker GFAP increased after prenatal exposure. CONCLUSION: We conclude that exogenously supplied CO during the prenatal period promotes oxidative stress as indicated by the up-regulation of SOD-1, SOD-2, HO-1, Ferritin-H, and iNOS with increased nitrotyrosine in the rat cerebella suggesting that deleterious and protective mechanisms were activated. These changes correlate with reductions of proteins important to cerebellar function: pre-synaptic terminals proteins (synapsin-1), proteins for the maintenance of neuronal size, shape and axonal quality (neurofilaments) and protein involved in GABAergic neurotransmission (GAD). Increased GFAP immunoreactivity after prenatal CO-exposure suggests a glial mediated response to the constant presence of CO. There were differential responses to prenatal vs. postnatal CO exposure: Prenatal exposure seems to be more damaging; a feature exemplified by the persistence of markers indicating oxidative stress in pups at P20, following prenatal only CO-exposure. The continuation of this cellular environment up to day 20 after CO exposure suggests the condition is chronic. Postnatal exposure without prenatal exposure shows the least impact, whereas prenatal followed by postnatal exposure exhibits the most pronounced outcome among the groups.
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Intoxicação por Monóxido de Carbono/patologia , Cerebelo/embriologia , Cerebelo/crescimento & desenvolvimento , Cerebelo/fisiopatologia , Estresse Oxidativo/fisiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Animais , Animais Recém-Nascidos , Apoferritinas/metabolismo , Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/fisiopatologia , Cerebelo/patologia , Modelos Animais de Doenças , Embrião de Mamíferos , Feminino , Heme Oxigenase-1/metabolismo , Masculino , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Gravidez , RNA Mensageiro/metabolismo , Ratos , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
INTRODUCTION: Elevated levels of plasma brain natriuretic peptide (BNP) and amino-terminal BNP (NT-proBNP) are associated with adverse cardiac outcomes. It is not known whether BNP and NT-proBNP levels in heart donors can aid in selection and predict outcomes in transplant recipients. METHODS: Plasma BNP and NT-proBNP were measured in 32 organ donors prior to removal from life-support systems. Twelve hearts were accepted and 20 hearts were declined (no suitable recipient - 12, probable coronary artery disease - four, abnormal echocardiogram - three, other medical reasons - one). Records of heart transplant recipients were reviewed for: survival at 30 d, length of intensive care stay and need for intra-aortic balloon counter-pulsation (IABP). RESULTS: Donors were divided into three groups - Group 1 (n = 12): accepted hearts; Group 2 (n = 12): acceptable hearts not transplanted for logistic reasons; Group 3 (n = 8): declined because of probable cardiac disease. BNP and NT-proBNP levels were significantly lower in donors with acceptable hearts (n = 24) compared with those with unacceptable hearts (n = 8) (p = 0.02 and 0.032, respectively). Of the 12 patients transplanted, four suffered a suboptimal outcome (two died, one required inotropic support and IABP, one prolonged hospitalization) while eight had good outcomes with no significant difference in BNP/NT-proBNP levels between these groups. CONCLUSION: BNP and NT-proBNP levels were lower in organ donors whose hearts were acceptable for transplantation compared with those whose hearts were unsuitable. Measuring natriuretic peptides may be a useful adjunctive tool in the selection of donor hearts. We feel that further studies are warranted.
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Cardiopatias/sangue , Transplante de Coração , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Precursores de Proteínas/sangue , Doadores de Tecidos , Adulto , Feminino , Cardiopatias/cirurgia , Humanos , Masculino , Estudos Prospectivos , Resultado do TratamentoRESUMO
Multiple unstable plaques have been demonstrated by various imaging techniques in culprit and nonculprit arteries in patients with acute coronary syndromes, but the frequency with which clinical manifestations of multiple unstable plaques occur is unclear. To estimate this frequency in patients who present within 6 hours with ST-elevation myocardial infarction, we studied electrocardiograms and cardiac marker levels of 722 patients with suspected reinfarction in the HERO-2 trial of 17,073 patients; this trial compared intravenous bivalirudin with unfractionated heparin before administration of streptokinase. Twenty-six patients (3.6%) developed recurrent ST elevation in a different territory. Of all the patients who developed ST elevation in a different territory, 50% (13 of 26) did so during the 48 hours of randomized antithrombin therapy compared with 29% (140 of 487) of those who developed recurrent ST elevation in the index territory (p = 0.046). Recurrent index territory ST elevation occurred in 392 of 552 patients (71%) with confirmed reinfarction, and ST elevation in a new territory occurred in 21 patients (3.8%) with confirmed reinfarction (2.3% and 0.12% of all HERO-2 enrollees, respectively). These data suggest that clinical manifestation of multiple unstable plaques of recurrent ST elevation and reinfarction in a territory different from that of the index ST elevation myocardial infarction after intravenous fibrinolytic and antithrombin therapies is rare.
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Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/fisiopatologia , Idoso , Anticoagulantes/uso terapêutico , Eletrocardiografia , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Recidiva , Terapia Trombolítica , Fatores de TempoRESUMO
Standard noninvasive recordings of the auditory brainstem evoked response (ABR) from a single pair of obliquely oriented electrodes (typically midline vertex referenced to mastoid) confound inherently distinct signals propagating over peripheral and central neural pathways differing in location and spatial orientation. We describe here a technique for recording short-latency auditory evoked potentials that putatively differentiates peripheral and central neural activity in the mouse and rat. The technique involves recording from two orthogonally oriented electrode pairs using fast sample rates (100 k/s) to accurately measure differences in neural timing and waveform morphology. Electrodes oriented in a transverse plane (mastoid-to-mastoid) register an initial positive-going ABR peak (P1T) earlier than a series of peaks recorded from electrodes oriented along the midline (anterior and posterior to the inter-aural line). The absolute P1T latency is consistent with an origin in the primary auditory nerve, while the delayed midline latencies implicate activity farther along central neural pathways. Differences between these latencies (midline minus transverse) provide new and precise measures of central conduction time (CCT), which in one case is as brief as 0.10 ms. Results in wild type (WT) and knockout (KO) mice, as well as rats, show significant differences in absolute latencies as well as CCT.
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Sistema Nervoso Central/fisiologia , Eletrodos , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Vias Neurais/fisiologia , Nervos Periféricos/fisiologia , Estimulação Acústica/métodos , Animais , Animais Recém-Nascidos , Eletroencefalografia/métodos , Processamento Eletrônico de Dados , Potenciais Evocados Auditivos do Tronco Encefálico/genética , Frequência Cardíaca/fisiologia , Frequência Cardíaca/efeitos da radiação , Camundongos , Camundongos Knockout , Vias Neurais/efeitos da radiação , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/deficiência , Ratos , Tempo de Reação/fisiologia , Peptídeo Intestinal Vasoativo/deficiênciaRESUMO
Iron deficiency and chronic mild carbon monoxide (CO) exposure are nutritional and environmental problems that can be experienced simultaneously. We examined the effects of chronic mild CO exposure and iron availability on auditory development in the rat. We propose that chronic mild CO exposure creates an oxidative stress condition that impairs the spiral ganglion neurons. The CO-exposed rat pups had decreased neurofilament proteins and increased copper, zinc-superoxide dismutase (SOD1) in the spiral ganglion neurons. We conclude that the increased amount of SOD1 causes an increase in hydrogen peroxide production that allows the Fenton reaction to occur. This reaction uses both iron and hydrogen peroxide to generate hydroxyl radicals and leads to the development of oxidative stress that impairs neuronal integrity. However, rat pups with decreased iron and CO exposure (ARIDCO) exhibited in their cochlea an up-regulation of transferrin, whereas their expression of neurofilament proteins and SOD1 were similar to control. Consequently, reduced iron availability and the normal expression of SOD1 do not promote oxidative stress in the cochlea. By using basal c-Fos expression as a marker for cellular activation we found a significant reduction in c-Fos expression in the central nucleus of the inferior colliculus in iron-adequate rat pups exposed to CO. By contrast, rather than being reduced, c-Fos expression in the ARIDCO group is the same as for controls. We conclude that the cochlea of rat pups with normal iron availability is selectively affected by mild CO exposure, causing a chronic oxidative stress, whereas limiting iron availability ameliorates the effect caused by mild CO exposure by averting conditions that facilitate oxidative stress.
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Intoxicação por Monóxido de Carbono/metabolismo , Cóclea/crescimento & desenvolvimento , Cóclea/metabolismo , Colículos Inferiores/crescimento & desenvolvimento , Colículos Inferiores/metabolismo , Ferro/farmacologia , Animais , Vias Auditivas/crescimento & desenvolvimento , Vias Auditivas/metabolismo , Monóxido de Carbono/toxicidade , Hematócrito , Substitutos do Leite , Proteínas de Neurofilamentos/metabolismo , Estresse Oxidativo/fisiologia , Ratos , Índice de Gravidade de Doença , Gânglio Espiral da Cóclea/crescimento & desenvolvimento , Gânglio Espiral da Cóclea/metabolismoRESUMO
The direct thrombin inhibitors hirudin and bivalirudin inhibit both fluid-phase and clot-bound thrombin. These agents have been extensively studied in clinical trials in comparison with intravenous unfractionated heparin (UFH), as adjuncts to fibrinolytic therapy for ST-elevation myocardial infarction (STEMI) and in percutaneous coronary intervention (PCI), and they are currently undergoing further evaluation in patients with non-ST elevation acute coronary syndromes (NSTEACS). In angiographic trials there were trends for patients treated with hirudin to be more likely to achieve Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow at 90 minutes than patients treated with UFH (65% versus 57% in TIMI-5; 41% versus 33% in Hirudin for the Improvement of Thrombolysis [HIT]-4; statistically nonsignificant differences in both trials). In Montréal Heart Institute trials and the multicenter Hirulog and Early Reperfusion or Occlusion (HERO)-1 trial the use of bivalirudin was associated with an increased incidence of TIMI grade 3 flow (85% versus 31%, p = 0.006; and 48% versus 35%, p = 0.02, respectively). These studies used streptokinase as the fibrinolytic agent except in TIMI-5 where alteplase was used. The initial clinical outcomes studies (Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes [GUSTO]-IIA and TIMI-9A) were discontinued early because of a high incidence of intracerebral bleeding (approximately 1.8%). Patients in these studies had either STEMI or NSTEACS, and thus not all were treated with fibrinolytic therapy. These studies were recommenced as GUSTO-IIB and TIMI-9B, using lower dosages of hirudin (0.1 mg/kg bolus + 0.1 mg/kg infusion for 96 hours). Neither TIMI-9B nor GUSTO-IIB showed an improvement in efficacy (death or reinfarction) or an increase in bleeding with hirudin. However, in the 1015 patients with STEMI treated with streptokinase in GUSTO-IIB, there was a 40% reduction in the combined incidence of death or myocardial infarction at 30 days (8.6% versus 14.4%, odds ratio [OR] 0.57, 95% confidence interval [CI] 0.38-0.87, p = 0.004). In the HERO-2 trial, 17073 patients receiving streptokinase for STEMI were randomized to receive either bivalirudin (0.25 mg/kg bolus and 0.5 mg/kg infusion for 12 hours followed by 0.25 mg/kg) or UFH (5000 IU bolus and 800-1000 IU/h infusion titrated to an activated partial thromboplastin time [APTT] of 50-75 seconds) for a total of 48 hours. Thirty-day mortality was similar in both groups (10.8% with bivalirudin versus 10.9% with UFH, OR 0.99, 95% CI 0.90-1.09, p = 0.85). There was a 30% reduction in the incidence of reinfarction before 96 hours (1.6% with bivalirudin versus 2.3% with UFH, OR 0.70, 95% CI 0.56-0.87, p = 0.001). Patients treated with bivalirudin had significantly more moderate bleeding (1.4% versus 1.1% with UFH, OR 1.32, 95% CI 1.0-1.74, p = 0.05). In a meta-analysis of patients with STEMI in the Direct Thrombin Inhibitor Trialists' collaboration, direct thrombin inhibitors were found to reduce the rate of reinfarction at 30 days (3.9% versus 4.8% with UFH, OR 0.80, 95% CI 0.71-0.90, p < 0.001), but did not reduce mortality (9.1% versus 9.0%, OR 1.02, 95% CI 0.94-1.11, p = 0.68) or the combined incidence of death/reinfarction at 30 days (11.8% versus 12.4%, OR 0.95, 95% CI 0.88-1.02, p = 0.18). There was no increase in major bleeding or intracerebral bleeding with direct thrombin inhibitor therapy. In conclusion, direct thrombin inhibitors reduce reinfarction, but not mortality, in patients with STEMI treated with fibrinolytic therapy. The major benefit of direct thrombin inhibitors appears to be in patients undergoing PCI, particularly after STEMI.
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Fibrinolíticos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Trombina/antagonistas & inibidores , Trombose/prevenção & controle , Angiografia Coronária , Eletrocardiografia , Humanos , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We have examined the influence of chronic mild exposure to carbon monoxide (CO) on cognitive (learning) and auditory function in the developing rat. We have demonstrated that the auditory pathway is compromised at exposures less than 50 ppm, whereas learning was not influenced at 100 ppm. Artificially reared rat pups were exposed to CO during the brain growth spurt and onset of myelination. Spatial learning was assessed using the Morris Water Maze and three tests of auditory function: (1) auditory brainstem conduction times; (2) the amplitude of the eighth nerve's action potential; and (3) otoacoustic emissions carried out on rat pups (age 22- 24 days). The pups were gastrostomy-reared on a rat milk substitute and chronically exposed to CO at discrete concentrations in the range of 12-100 ppm from 6 days of age to post-weaning at 21-23 days of age. We found no difference in auditory brainstem conduction times at all CO concentrations in comparison to non-exposed controls. There was a difference in otoacoustic emissions for test and controls at CO concentrations of 50 ppm but not at lower concentrations. There was a consistent attenuation of the amplitude of the eighth nerve's action potential, even at the lowest CO exposure examined. The attenuation of the amplitude of the action potential of the eighth nerve at 50 ppm carbon monoxide exposure did not completely recover by 73 days of age. We conclude that prolonged mild exposure to carbon monoxide during development causes measurable functional changes at the level of the eighth cranial nerve.
Assuntos
Vias Auditivas/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Monóxido de Carbono/toxicidade , Cognição/efeitos dos fármacos , Estimulação Acústica , Potenciais de Ação/efeitos dos fármacos , Animais , Vias Auditivas/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Privação Materna , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Nervo Vestibulococlear/efeitos dos fármacosRESUMO
The object of this study was to determine if chronic exposure to mild concentrations of CO in air caused changes in the integrity of the inferior colliculus during the most active period of synaptogenesis/auditory development. We examined all subregions of the inferior colliculus (IC) of rats by immunocytochemical approaches after pups were exposed chronically to CO concentrations of, 0, 12.5, 25, and 50 ppm in air starting at Day 8 through 20-22 days of age. Mother-reared pups were compared to the gastrostomy-reared pups with or without CO exposure for basal neural activity, using c-Fos immunoreactivity as a marker. Half the rats were examined at 27 days of age, 5 days after the end of CO exposure, and the other half were examined 50 days later at 75-77 days of age. In the central nucleus of the IC, the number of cells expressing a basal level of c-Fos was decreased significantly in the CO-exposed animals when compared to controls; however, there was little or no difference in the number of cells expressing c-Fos in the other subregions of the IC. We conclude that the central nucleus of the inferior colliculus is affected selectively by mild CO exposure (0.0012% in air) and that this reduction in neuronal activity persists into adulthood.
Assuntos
Vias Auditivas/efeitos dos fármacos , Monóxido de Carbono/toxicidade , Colículos Inferiores/efeitos dos fármacos , Animais , Vias Auditivas/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Imuno-Histoquímica , Colículos Inferiores/crescimento & desenvolvimento , Privação Materna , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/fisiologia , Ratos , Fatores de TempoRESUMO
Rat pups were chronically exposed to carbon monoxide (CO) concentrations (12 or 25 ppm) in air starting at day 8, through 22 days of age, to examine the changes in the peripheral auditory system. Gastrostomy-reared rat pups, with or without CO exposure, were used and compared with mother-reared pups. The organ of Corti and the neurons of the spiral ganglion were analyzed for their morphology by using immunochemical and histological techniques. The inner and outer hair cells in the organ of Corti of animals exposed to 12 and 25 ppm CO were not different from the controls. However, at 25 ppm CO exposure, the nerve terminals innervating the inner hair cells were swollen. The somata of neurons in the spiral ganglion showed mild changes in the cytoplasm, and signs of mild vacuolization were observed in myelin covering their central processes. Synaptophysin, a marker for synaptic vesicles, and choline acetyltransferase, a marker for cholinergic terminals, showed no difference in immunoreactivity in CO exposed animals at 12 and at 25 ppm when compared with their age-matched controls. Also, Na(+)K(+) ATPase immunoreactivity patterns were normal compared with controls. Three enzymes were significantly reduced at the 25 ppm CO exposure: Cytochrome oxidase, NADH-TR, and calcium ATPase were decreased in both the organ of Corti and the neurons of the spiral ganglion, and decreased immunostaining for the neurofilament and myelin basic proteins was found. We conclude that components of the cochlea are selectively affected by mild chronic CO exposure during development.
Assuntos
Monóxido de Carbono/toxicidade , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/patologia , Animais , Relação Dose-Resposta a Droga , Células Ciliadas Auditivas/crescimento & desenvolvimento , Imuno-Histoquímica , Privação Materna , Ratos , Ratos Sprague-Dawley , Gânglio Espiral da Cóclea/efeitos dos fármacos , Gânglio Espiral da Cóclea/crescimento & desenvolvimento , Gânglio Espiral da Cóclea/patologiaRESUMO
UNLABELLED: Previous studies found that juvenile offspring of rats fed high docosahexaenoic acid (DHA; 22:6n-3) diets through gestation and lactation had longer auditory brainstem-evoked response (ABR) accompanied by higher 22:6n-3 and lower arachidonic acid (ARA; 20:4n-6) in brain. In the present study, ABR was assessed in juvenile rats fed high-DHA diets only postnatally. METHODS: Rat pups were fed rat milk formulas with varying amounts of DHA and ARA to 19 days of age followed by diets with the corresponding fatty acids. The high-DHA group was fed 2.3% of fatty acids as DHA, the DHA + ARA group was fed DHA and ARA at 0.6 and 0.4% of fatty acids, levels similar to those in some infant formulas, and the unsupplemented group was fed no DHA or ARA. ABR and fatty acid and monoamine levels in brain were measured on postnatal days 26-28. Statistical analyses were measured by ANOVA. RESULTS: ARA and DHA levels in brain increased with supplementation. ABR was shorter in the high-DHA group than the DHA + ARA group and not different from the unsupplemented or dam-reared suckling group. Norepinephrine levels in the inferior colliculus were lower in the high-DHA group than the DHA + ARA group and higher in all formula groups compared to the dam-reared group. CONCLUSION: In contrast to the longer ABR in juvenile offspring of rats fed high-DHA through gestation and lactation, ABR was shorter in juvenile rats fed high-DHA diets only after birth than rats fed ARA + DHA. Further studies are needed to understand the relationship between dietary DHA, norepinephrine, and auditory system development over a range of DHA intakes and discrete periods of development.
Assuntos
Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/análise , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Alimentos Formulados/análise , Leite , Animais , Ácido Araquidônico/administração & dosagem , Ácido Araquidônico/análise , Monoaminas Biogênicas/análise , Encéfalo/crescimento & desenvolvimento , Química Encefálica , Ácidos Graxos/análise , Colículos Inferiores/química , Tamanho do Órgão , Fosfolipídeos/análise , Ratos , Ratos Sprague-Dawley , Aumento de PesoRESUMO
A case of emergency stent deployment to a critical vein graft lesion in a patient with an acute myocardial infarction and cardiogenic shock is described. An Angioguard vascular protection device was used, retrieving a large amount of atheromatous debris. Use of filter-type protection devices to prevent distal atheroembolism may be lifesaving in such patients.
Assuntos
Embolia de Colesterol/prevenção & controle , Oclusão de Enxerto Vascular/terapia , Infarto do Miocárdio/complicações , Próteses e Implantes , Veia Safena/transplante , Choque Cardiogênico/complicações , Stents , Idoso , Filtração/métodos , Humanos , MasculinoRESUMO
AIMS: To prospectively evaluate the efficacy and safety of a chest pain pathway at Green Lane Hospital. METHODS: Between August 1999 and March 2000, patients with non-traumatic chest discomfort considered to be possibly ischaemic were assessed by history, physical examination, baseline electrocardiographic findings and point of care troponin T tests. Those considered not to be high risk entered the pathway which included repeat cardiac markers and electrocardiograms at 6-8 hours, followed by optional stress testing. The patients were followed for at least one year. RESULTS: Of 423 patients with chest discomfort compatible with myocardial ischaemia, 173 were enrolled in the pathway, with 19 later transferred off the pathway for clinical reasons. Of the remaining 154 patients, the median duration of hospital stay was 17.3 hours [IQR 8.2, 25.1] (median of 13.1 hours for those who did not undergo stress testing); 111 (72%) stayed in hospital for less than 24 hours. There were no readmissions within 30 days with an acute coronary syndrome. In the year following discharge, three patients had a myocardial infarction (one of whom later died) and four died of non-cardiac causes. At one year, freedom from cardiac death or non-fatal myocardial infarction was 98% [95%CI 95,100]. CONCLUSIONS: The chest pain pathway facilitated patient triage and patients had high event-free survival.