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1.
Radiography (Lond) ; 28(1): 102-106, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34481711

RESUMO

INTRODUCTION: To offer citizens with frailty or dementia living in nursing homes or other institutions a less stressful and anxious X-ray examination, a Danish hospital offers to perform the examination in the citizen's residence. This has changed the working procedure for the radiographers performing the examination. The aim of this study was to explore if the radiographers self-perceived competencies have changed whilst working in the mobile X-ray unit and if so, how these competencies are utilised within the department-based medical imaging team. METHOD: This study had a qualitative design following a hermeneutic approach. Individual semi structured interviews included nine radiographers, four radiographers working in the mobile X-ray unit and five radiographers working exclusively in the medical imaging team. RESULTS: Radiographers who worked in the mobile X-ray unit did acquire new competencies such as better communication and creative positioning skills. All nine participants recognised the advantage of sharing experiences and competencies with colleagues, and recommended a formal forum to do so. They sought opportunities for the use of the mobile X-ray unit to be more widespread within their own region, and within the profession. CONCLUSION: This study indicates that radiographers working with mobile X-ray unit gained new competencies in communication and positioning, but without spread of new knowledge to colleagues in the medical imaging team. IMPLICATION FOR PRACTICE: The use of home-based mobile X-ray is a new way to provide health care services and gain new competencies for the radiographers to focus on patient centred care.


Assuntos
Pessoal Técnico de Saúde , Casas de Saúde , Humanos , Radiografia , Raios X
2.
Epidemiol Infect ; 145(13): 2787-2796, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28768556

RESUMO

The spread of African swine fever virus (ASFV) threatens to reach further parts of Europe. In countries with a large swine production, an outbreak of ASF may result in devastating economic consequences for the swine industry. Simulation models can assist decision makers setting up contingency plans. This creates a need for estimation of parameters. This study presents a new analysis of a previously published study. A full likelihood framework is presented including the impact of model assumptions on the estimated transmission parameters. As animals were only tested every other day, an interpretation was introduced to cover the weighted infectiousness on unobserved days for the individual animals (WIU). Based on our model and the set of assumptions, the within- and between-pen transmission parameters were estimated to ß w = 1·05 (95% CI 0·62-1·72), ß b = 0·46 (95% CI 0·17-1·00), respectively, and the WIU = 1·00 (95% CI 0-1). Furthermore, we simulated the spread of ASFV within a pig house using a modified SEIR-model to establish the time from infection of one animal until ASFV is detected in the herd. Based on a chosen detection limit of 2·55% equivalent to 10 dead pigs out of 360, the disease would be detected 13-19 days after introduction.


Assuntos
Vírus da Febre Suína Africana/fisiologia , Febre Suína Africana/transmissão , Febre Suína Africana/diagnóstico , Febre Suína Africana/virologia , Animais , Abrigo para Animais , Modelos Teóricos , Suínos , Reino Unido
3.
Am J Physiol Heart Circ Physiol ; 308(8): H823-9, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25637547

RESUMO

Although exercise training has been demonstrated to have beneficial cardiovascular effects in diabetes, the effect of exercise training on hearts from obese/diabetic models is unclear. In the present study, mice were fed a high-fat diet, which led to obesity, reduced aerobic capacity, development of mild diastolic dysfunction, and impaired glucose tolerance. Following 8 wk on high-fat diet, mice were assigned to 5 weekly high-intensity interval training (HIT) sessions (10 × 4 min at 85-90% of maximum oxygen uptake) or remained sedentary for the next 10 constitutive weeks. HIT increased maximum oxygen uptake by 13%, reduced body weight by 16%, and improved systemic glucose homeostasis. Exercise training was found to normalize diastolic function, attenuate diet-induced changes in myocardial substrate utilization, and dampen cardiac reactive oxygen species content and fibrosis. These changes were accompanied by normalization of obesity-related impairment of mechanical efficiency due to a decrease in work-independent myocardial oxygen consumption. Finally, we found HIT to reduce infarct size by 47% in ex vivo hearts subjected to ischemia-reperfusion. This study therefore demonstrated for the first time that exercise training mediates cardioprotection following ischemia in diet-induced obese mice and that this was associated with oxygen-sparing effects. These findings highlight the importance of optimal myocardial energetics during ischemic stress.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Consumo de Oxigênio , Esforço Físico , Disfunção Ventricular/prevenção & controle , Animais , Fibrose/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Obesidade/complicações , Obesidade/etiologia , Espécies Reativas de Oxigênio/metabolismo , Disfunção Ventricular/etiologia , Disfunção Ventricular/fisiopatologia
4.
Chem Commun (Camb) ; 50(58): 7800-2, 2014 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-24903342

RESUMO

A coupling reaction between secondary propargyl amines and isothiocyanates in aqueous media is described. The reaction is high-yielding and affords cyclized products within 2-24 h. A functionalized ether lipid was synthesized in 8 steps, formulated as liposomes with POPC and conjugated to FITC under mild conditions using this method.


Assuntos
Isotiocianatos/química , Pargilina/análogos & derivados , Propilaminas/química , Cromatografia Líquida de Alta Pressão , Ciclização , Pargilina/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Tiazolidinas/síntese química
5.
J Appl Physiol (1985) ; 111(5): 1235-41, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21836050

RESUMO

AIMS: although exercise training induces hypertrophy with improved contractile function, the effect of exercise on myocardial substrate metabolism and cardiac efficiency is less clear. High intensity training has been shown to produce more profound effects on cardiovascular function and aerobic capacity than isocaloric low and moderate intensity training. The aim of the present study was to explore metabolic and mechanoenergetic changes in the heart following endurance exercise training of both high and moderate intensity. METHODS AND RESULTS: C57BL/6J mice were subjected to 10 wk treadmill running, either high intensity interval training (HIT) or distance-matched moderate intensity training (MIT), where HIT led to a pronounced increase in maximal oxygen uptake. Although both modes of exercise were associated with a 10% increase in heart weight-to-body weight ratio, only HIT altered cardiac substrate utilization, as revealed by a 36% increase in glucose oxidation and a concomitant reduction in fatty acid oxidation. HIT also improved cardiac efficiency by decreasing work-independent myocardial oxygen consumption. In addition, it increased cardiac maximal mitochondrial respiratory capacity. CONCLUSION: This study shows that high intensity training is required for induction of changes in cardiac substrate utilization and energetics, which may contribute to the superior effects of high compared with moderate intensity training in terms of increasing aerobic capacity.


Assuntos
Tolerância ao Exercício/fisiologia , Coração/fisiologia , Miocárdio/metabolismo , Consumo de Oxigênio/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Peso Corporal/fisiologia , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatologia , Respiração Celular/fisiologia , Citrato (si)-Sintase/metabolismo , Ácidos Graxos/metabolismo , Glucose/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/fisiologia
6.
Ann Hematol ; 87(10): 847-50, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18481066

RESUMO

Quantitative assessment of the JAK2 V617F allele burden during disease evolution and ongoing myelosuppressive treatment is likely to be implemented in the future clinical setting. Interferon alpha has demonstrated efficacy in treatment of both chronic myeloid leukemia and the Philadelphia chromosome negative chronic myeloproliferative disorders. Reductions in the JAK2 V617F allele burden in patients treated with pegylated interferon alpha-2a (Peg-IFN-2a) have been demonstrated, although follow-up was relatively short. We report here the first profound and sustained molecular responses with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response.


Assuntos
Interferon-alfa/uso terapêutico , Janus Quinase 2/genética , Policitemia Vera/tratamento farmacológico , Policitemia Vera/genética , Adulto , Alelos , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Policitemia Vera/imunologia , Proteínas Recombinantes
7.
Colorectal Dis ; 10(9): 869-72, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18384423

RESUMO

OBJECTIVE: Laparoscopic colonic surgery was introduced about 15 years ago and has together with the evidence-based 'fast-track' methodology improved early postoperative outcome. The purpose of this study was to asses the organization and early outcome after laparoscopic colonic surgery in Denmark from 2004 to 2007. METHOD: Based upon the National Patient Register, all laparoscopic colonic operations performed in Denmark between January 2004 and December 2006 were analysed regarding number of hospital departments and procedures, hospital stay, readmissions and mortality. RESULTS: One thousand one hundred and forty-nine laparoscopic colonic resections without simultaneous stoma formation were performed in the study period. Twenty-five departments performed the procedures but only four departments performed more than 100 procedures. The median length of primary stay was 4 days (mean 7.7 days). One hundred and twenty-five (10.9%) patients were re-admitted within 30 days and total length of stay (primary plus readmissions) was a median of 5 days (mean 8.5 days). Thirty-day mortality was 2.6% and hospital mortality 3.5%. CONCLUSION: This nationwide study has shown an increased implementation of laparoscopic colonic surgery but probably performed in too many low volume departments. Laparoscopic colonic surgery should be monitored and further advances secured by adjustment of perioperative care to fast-track care.


Assuntos
Doenças do Colo/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Laparoscopia , Avaliação de Resultados em Cuidados de Saúde , Dinamarca , Mortalidade Hospitalar , Humanos , Tempo de Internação , Readmissão do Paciente/estatística & dados numéricos , Centro Cirúrgico Hospitalar/estatística & dados numéricos
9.
Arch Physiol Biochem ; 113(4-5): 211-20, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18158644

RESUMO

Isolated perfused hearts from type 2 diabetic (db/db) mice show impaired ventricular function, as well as altered cardiac metabolism. Assessment of the relationship between myocardial oxygen consumption (MVO(2)) and ventricular pressure-volume area (PVA) has also demonstrated reduced cardiac efficiency in db/db hearts. We hypothesized that lowering the plasma fatty acid supply and subsequent normalization of altered cardiac metabolism by chronic treatment with a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist will improve cardiac efficiency in db/db hearts. Rosiglitazone (23 mg/kg body weight/day) was administered as a food admixture to db/db mice for five weeks. Ventricular function and PVA were assessed using a miniaturized (1.4 Fr) pressure-volume catheter; MVO(2) was measured using a fibre-optic oxygen sensor. Chronic rosiglitazone treatment of db/db mice normalized plasma glucose and lipid concentrations, restored rates of cardiac glucose and fatty acid oxidation, and improved cardiac efficiency. The improved cardiac efficiency was due to a significant decrease in unloaded MVO(2), while contractile efficiency was unchanged. Rosiglitazone treatment also improved functional recovery after low-flow ischemia. In conclusion, the present study demonstrates that in vivo PPARgamma-treatment restores cardiac efficiency and improves ventricular function in perfused hearts from type 2 diabetic mice.


Assuntos
Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Diabetes Mellitus Tipo 2/fisiopatologia , Coração/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Coração/fisiologia , Coração/fisiopatologia , Canais Iônicos/metabolismo , Isquemia/fisiopatologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Traumatismo por Reperfusão , Rosiglitazona , Tiazolidinedionas/uso terapêutico , Proteína Desacopladora 3 , Função Ventricular/efeitos dos fármacos
11.
Acta Physiol (Oxf) ; 186(3): 171-7, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16497196

RESUMO

AIM: The aim of the present study was to compare the coronary flow (CF) reserve of ex vivo perfused hearts from type 2 diabetic (db/db) and non-diabetic (db/+) mice. METHODS: The hearts were perfused in the Langendorff mode with Krebs-Henseleit bicarbonate buffer (37 degrees C, pH 7.4) containing 11 mmol L(-1) glucose as energy substrate. The coronary reserve was measured in response to three different interventions: (1) administration of nitroprusside (a nitric oxide donor), (2) administration of adenosine and (3) production of reactive hyperaemia by short-term ischaemia. RESULTS: Basal CF was approximately 15% lower in diabetic when compared with non-diabetic hearts (2.1 +/- 0.1 vs. 2.6 +/- 0.2 mL min(-1)). The maximum increase in CF rate in response to sodium nitroprusside and adenosine was significantly lower in diabetic (0.6 +/- 0.1 and 0.9 +/- 0.1 mL min(-1) respectively) than in non-diabetic hearts (1.2 +/- 0.1 and 1.4 +/- 0.1 mL min(-1) respectively). Also, there was a clear difference in the rate of return to basal CF following short-term ischaemia between diabetic and non-diabetic hearts. Thus, basal tone was restored 1-2 min after the peak hyperaemic response in non-diabetic hearts, whereas it took approximately 5 min in diabetic hearts. CONCLUSION: These results show that basal CF, as well as the CF reserve, is impaired in hearts from type 2 diabetic mice. As diabetic and non-diabetic hearts were exposed to the same (maximum) concentrations of NO or adenosine, it is suggested that the lower coronary reserve in type 2 diabetic hearts is, in part, because of a defect in the intracellular pathways mediating smooth muscle relaxation.


Assuntos
Circulação Coronária , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Adenosina/farmacologia , Animais , Peso Corporal , Circulação Coronária/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Ácidos Láuricos/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Nitroprussiato/farmacologia , Técnicas de Cultura de Órgãos , Vasodilatadores/farmacologia
12.
Acta Physiol Scand ; 181(2): 167-72, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15180788

RESUMO

AIM: Langendorff-perfused murine hearts are increasingly used in cardiovascular research, but coronary cardiovascular haemodynamics vary considerably from one research group to another. The aim of this study was to establish an isolated, retrogradely perfused mouse heart preparation for the simultaneous measurement of left ventricular haemodynamics and of coronary flow (CF). METHODS: Heart rate was controlled by right atrial pacing (480 beats min(-1)) and heart temperature was kept constant. Accurate flow values of <0.5 mL min(-1) could be determined, and this methodology was then used to study the stability of this preparation, as well as coronary response to vasoactive drugs and to short-term ischaemia. RESULTS: The CF and maximum systolic pressure were well maintained over a 2-h perfusion period, both showing a 10% decline per hour. Sodium-nitroprusside (endothelium-independent) and adenosine (endothelium-dependent) increased CF relatively modest (30-50% above baseline values). Short-term no-flow ischaemia caused a transient 40-50% increase in CF on reperfusion. Peak reflow occurred approximately 15 s after start of reperfusion and flow returned to baseline during the following 1-2 min. Increased coronary blood flow following infusion of vasoactive drugs (nitroprusside or adenosine) or short-term ischaemia were associated with minor changes in ventricular pressure development. CONCLUSIONS: Blood flow and haemodynamics can readily be determined in this isolated perfused mouse heart model, but CF reserve is relatively small, compared with blood-perfused organs.


Assuntos
Circulação Coronária/fisiologia , Função Ventricular Esquerda/fisiologia , Adenosina/farmacologia , Animais , Pressão Sanguínea/fisiologia , Circulação Coronária/efeitos dos fármacos , Camundongos , Isquemia Miocárdica/fisiopatologia , Reperfusão Miocárdica/métodos , Nitroprussiato/farmacologia , Técnicas de Cultura de Órgãos , Vasodilatadores/farmacologia
13.
Nature ; 413(6858): 848-52, 2001 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-11677608

RESUMO

Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.


Assuntos
Genoma Bacteriano , Salmonella typhi/genética , Mapeamento Cromossômico , Cromossomos Bacterianos , DNA Bacteriano , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/genética , Deleção de Genes , Humanos , Dados de Sequência Molecular , Mutagênese Insercional , Plasmídeos/genética , Recombinação Genética , Salmonella typhimurium/genética , Análise de Sequência de DNA , Sorotipagem
14.
Environ Pollut ; 114(2): 275-83, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11504350

RESUMO

Lead and zinc levels in sediments and biota from the fjord system surrounding the lead/zinc mine at Maarmorilik, West Greenland, were investigated to evaluate the impact of waste rock and marine-deposited tailings on the marine biota. Concentrations of metal in the sediment were up to 8,922 +/- 622 microg g(-1) (dry wt.) for lead and 19,351+/- 476 microg g(-1) (dry wt.) for zinc. Levels of lead and zinc were also elevated in a suite of monitor organisms. The feeding modes of the organisms were used to explain the sources of metals to the organisms. After closure of the mine, the concentrations of metals in the upper centimetres of the sediments decreased, and a decreased impact of metals on the brown alga Fucus distichus was observed. However, the metals in the sediments still affect the marine biota in the area.


Assuntos
Sedimentos Geológicos/química , Chumbo/análise , Eliminação de Resíduos , Zinco/análise , Animais , Monitoramento Ambiental , Groenlândia , Invertebrados/química , Chumbo/farmacocinética , Mineração , Phaeophyceae/química , Zinco/farmacocinética
15.
Biochimie ; 83(2): 201-12, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11278070

RESUMO

We have analysed the complete sequence of the Escherichia coli K12 isolate MG1655 genome for chromatin-associated protein binding sites, and compared the predicted location of predicted sites with experimental expression data from 'DNA chip' experiments. Of the dozen proteins associated with chromatin in E. coli, only three have been shown to have significant binding preferences: integration host factor (IHF) has the strongest binding site preference, and FIS sites show a weak consensus, and there is no clear consensus site for binding of the H-NS protein. Using hidden Markov models (HMMs), we predict the location of 608 IHF sites, scattered throughout the genome. A subset of the IHF sites associated with repeats tends to be clustered around the origin of replication. We estimate there could be roughly 6000 FIS sites in E. coli, and the sites tend to be localised in two regions flanking the replication termini. We also show that the regions upstream of genes regulated by H-NS are more curved and have a higher AT content than regions upstream of other genes. These regions in general would also be localised near the replication terminus.


Assuntos
Proteínas de Bactérias/genética , Cromatina/genética , DNA Bacteriano/genética , Proteínas de Ligação a DNA/genética , Proteínas de Escherichia coli , Escherichia coli/genética , Genoma Bacteriano , Sítios de Ligação , Proteínas de Transporte/metabolismo , Replicação do DNA , Fator Proteico para Inversão de Estimulação , Fatores Hospedeiros de Integração , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Óperon , Plasmídeos , Sequências Repetitivas de Ácido Nucleico
16.
Am J Physiol Endocrinol Metab ; 280(3): E420-7, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11171596

RESUMO

Glucose and fatty acid metabolism was assessed in isolated working hearts from control C57BL/KsJ-m+/+db mice and transgenic mice overexpressing the human GLUT-4 glucose transporter (db/+-hGLUT-4). Heart rate, coronary flow, cardiac output, and cardiac power did not differ between control hearts and hearts overexpressing GLUT-4. Hearts overexpressing GLUT-4 had significantly higher rates of glucose uptake and glycolysis and higher levels of glycogen after perfusion than control hearts, but rates of glucose and palmitate oxidation were not different. Insulin (1 mU/ml) significantly increased glycogen levels in both groups. Insulin increased glycolysis in control hearts but not in GLUT-4 hearts, whereas glucose oxidation was increased by insulin in both groups. Therefore, GLUT-4 overexpression increases glycolysis, but not glucose oxidation, in the heart. Although control hearts responded to insulin with increased rates of glycolysis, the enhanced entry of glucose in the GLUT-4 hearts was already sufficient to maximally activate glycolysis under basal conditions such that insulin could not further stimulate the glycolytic rate.


Assuntos
Expressão Gênica , Glucose/metabolismo , Proteínas de Transporte de Monossacarídeos/genética , Proteínas Musculares , Miocárdio/metabolismo , Animais , Desoxiglucose/metabolismo , Transportador de Glucose Tipo 4 , Glicogênio/metabolismo , Glicólise , Coração/efeitos dos fármacos , Humanos , Insulina/farmacologia , Cinética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas de Transporte de Monossacarídeos/fisiologia , Oxirredução , Ácido Palmítico/metabolismo , Perfusão , Trítio
18.
Am J Physiol Endocrinol Metab ; 279(5): E1104-13, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11052966

RESUMO

Contractile function and substrate metabolism were characterized in perfused hearts from genetically diabetic C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice and their non-diabetic lean littermates. Contractility was assessed in working hearts by measuring left ventricular pressures and cardiac power. Rates of glycolysis, glucose oxidation, and fatty acid oxidation were measured using radiolabeled substrates ([5-(3)H]glucose, [U-(14)C]glucose, and [9,10-(3)H]palmitate) in the perfusate. Contractile dysfunction in db/db hearts was evident, with increased left ventricular end diastolic pressure and decreased left ventricular developed pressure, cardiac output, and cardiac power. The rate of glycolysis from exogenous glucose in diabetic hearts was 48% of control, whereas glucose oxidation was depressed to only 16% of control. In contrast, palmitate oxidation was increased twofold in db/db hearts. The hypothesis that altered metabolism plays a causative role in diabetes-induced contractile dysfunction was tested using perfused hearts from transgenic db/db mice that overexpress GLUT-4 glucose transporters. Both glucose metabolism and palmitate metabolism were normalized in hearts from db/db-human insulin-regulatable glucose transporter (hGLUT-4) hearts, as was contractile function. These findings strongly support a causative role of impaired metabolism in the cardiomyopathy observed in db/db diabetic hearts.


Assuntos
Diabetes Mellitus/fisiopatologia , Proteínas Musculares , Contração Miocárdica , Animais , Glicemia/metabolismo , Pressão Sanguínea , Radioisótopos de Carbono , Débito Cardíaco , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Ácidos Graxos/sangue , Expressão Gênica , Transportador de Glucose Tipo 4 , Glicólise , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas de Transporte de Monossacarídeos/genética , Miocárdio/metabolismo , Oxirredução , Ácido Palmítico/sangue , Trítio , Função Ventricular Esquerda
19.
Ann Thorac Surg ; 69(6): 1799-805, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10892926

RESUMO

BACKGROUND: Warm continuous blood cardioplegia (WCBCP) has been recommended during prolonged cardiac arrest to minimize functional deterioration. Myocardial metabolism and efficiency after this cardioplegic modality are not well described. METHODS: Substrate oxidation, blood flow, and myocardial function were measured before, during, and after 3 hours of WCBCP in 7 pigs. RESULTS: Free fatty acid and glucose oxidation decreased by 60% +/- 3.8% and 94% +/- 1.2%, respectively, during cardioplegia (both p < 0.05) and increased to 62% +/- 28% and 122% +/- 62% of baseline during the early recovery phase (p < 0.05 for glucose). One hour after WCBCP oxidation rates were similar to baseline. The transient postcardioplegic increase in substrate oxidation was associated with a 43% +/- 23% elevation of oxygen consumption (MVO2) compared with baseline and a 62% +/- 18% increase in myocardial blood flow. Cardiac output and mean arterial pressure did not change significantly after WCBCP, although myocardial function (stroke work, left ventricular end-systolic pressure, end-diastolic pressure, contractility, and efficiency) was depressed (p < 0.05). End-diastolic pressure and contractility improved from early to late phase of recovery, whereas the other indicators of ventricular function remained depressed. CONCLUSIONS: Myocardial substrate oxidation was preserved after 3 hours of WCBCP, although ventricular function was moderately impaired. Thus, WCBCP with a seemingly normal substrate and oxygen supply was associated with a reduced cardiac efficiency.


Assuntos
Metabolismo Energético/fisiologia , Parada Cardíaca Induzida , Miocárdio/metabolismo , Animais , Glicemia/metabolismo , Regulação da Temperatura Corporal/fisiologia , Ácidos Graxos não Esterificados/metabolismo , Feminino , Hemodinâmica/fisiologia , Masculino , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Consumo de Oxigênio/fisiologia , Perfusão , Suínos , Função Ventricular Esquerda/fisiologia
20.
Cardiovasc Drugs Ther ; 14(6): 615-23, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11300362

RESUMO

Coronary reperfusion improves ventricular function and survival after infarction, but the metabolic conditions at this time may not be optimal to protect the heart. The objective of this study was to evaluate if metabolic support with glucose-insulin-potassium (GIK) administered at the time of coronary reperfusion could elicit the same cardioprotection as GIK infusion during the entire ischemia/reperfusion period. Three groups of anesthetized, open-chest rats were subjected to 30 minutes of regional ischemia and 180 minutes of reperfusion. Groups 1 (controls) and 2 (GIK(IR)) received saline or GIK, respectively, throughout the whole experimental period, whereas a third group (GIK(R)) received GIK from the onset of reperfusion only. Infarct size was significantly reduced in the GIK-treated groups, compared with controls (GIK(IR) 44 +/- 5% and GIK(R) 45 +/- 5% vs. control 66 +/- 4%; P < 0.05). Postischemic recovery of cardiac function improved when GIK was only administered during the reperfusion phase. Furthermore, infusion of GIK resulted in reduced plasma concentrations of free fatty acids and increased plasma glucose (both P < 0.05) compared with controls. This study demonstrates that glucose-insulin-potassium administration at the onset of the postischemic reperfusion period is as cardioprotective as administration of GIK during the entire ischemia/reperfusion period.


Assuntos
Glucose/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/patologia , Potássio/uso terapêutico , Animais , Glicemia/metabolismo , Combinação de Medicamentos , Eletrólitos/sangue , Ácidos Graxos não Esterificados/sangue , Hipoglicemiantes/sangue , Insulina/sangue , Masculino , Concentração Osmolar , Potássio/sangue , Ratos , Ratos Sprague-Dawley , Função Ventricular Esquerda
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