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1.
J Cardiovasc Med (Hagerstown) ; 18(7): 459-466, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24979121

RESUMO

: Therapeutic hypothermia has been shown to reduce brain damage due to postcardiac arrest syndrome. Actually, there is no agreement on which is the best device to perform therapeutic hypothermia. The 'ideal' device should not only 'cool' patient until 33-34°C as fast as possible, but also maintain the target temperature and reverse the therapeutic hypothermia. For out-of-hospital cardiac arrest, there are devices that allow starting of therapeutic hypothermia on the field (prehospital hypothermia). On hospital arrival, these prehospital devices can be quickly and easily replaced with other devices more suitable for the management of therapeutic hypothermia in ICUs (in-hospital hypothermia). Some studies have compared surface and endovascular devices and found no substantial differences in neurologic outcome or survival at hospital discharge. On a clinical ground, the knowledge of the technical aspects of therapeutic hypothermia (such as characteristics of devices) is mandatory for clinicians who have to perform therapeutic hypothermia in cardiac arrest patients because the timing of therapeutic hypothermia, the choice of the device for the single patients, and avoidance of temperature fluctuation have shown to affect outcome in these patients (also in terms of reducing the incidence of complications).


Assuntos
Regulação da Temperatura Corporal , Parada Cardíaca/terapia , Hipotermia Induzida/métodos , Hipóxia Encefálica/prevenção & controle , Desenho de Equipamento , Parada Cardíaca/complicações , Parada Cardíaca/diagnóstico , Parada Cardíaca/fisiopatologia , Humanos , Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/instrumentação , Hipóxia Encefálica/diagnóstico , Hipóxia Encefálica/etiologia , Hipóxia Encefálica/fisiopatologia , Fatores de Risco , Tempo para o Tratamento , Resultado do Tratamento
2.
Minerva Anestesiol ; 82(10): 1043-1049, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26957118

RESUMO

BACKGROUND: The aim of this study was to assess the incidence and prognostic role of echocardiographic abnormalities in consecutive patients with refractory acute respiratory distress syndrome (ARDS) before veno-venous extracorporeal membrane oxygenation (VV-ECMO). METHODS: In this study 74 consecutive patients with refractory ARDS underwent echocardiography (transthoracic, transesophageal or both, according to the best acoustic window). Baseline characteristics were collected for all patients and the simplified acute physiology score was calculated. At echocardiography the following parameters were considered: left ventricle (LV) ejection fraction, right ventricle (RV) size and function (by means of tricuspid annular plane excursion [TAPSE]) and systolic pulmonary arterial pressure. RESULTS: At echocardiography, 25 patients showed normal findings (33.8%), 32 patients exhibited isolated pulmonary hypertension (43.2%) and the remaining 17 patients showed RV dilation and pulmonary hypertension (23%). A reduced LVEF (<50%) was observed in 14 patients (18.9%), while RV dysfunction (as indicated by TAPSE<16 mm) was documented in 21 patients (28.4%). The in-Intensive Care Unit [ICU] mortality rate was 41.8%. At stepwise regression analysis the following variables were independent predictor for in-ICU mortality (when adjusted for TAPSE<16 mm): RV end diastolic area/LV end diastolic area (OR 0.21, 95%CI 0.062-0.709, P=0.012), Body Mass Index (BMI) (OR 0.87, 95%CI 0.802-0.958, P=0.004) CONCLUSIONS: In consecutive patients with refractory ARDS, echocardiographic alterations were common, mainly represented by systolic pulmonary hypertension associated or not with RV dilatation. Moreover, RV dilatation and BMI were independent predictors of in-ICU mortality. On clinical grounds, our findings strongly suggest that echocardiography helps to risk stratifying patients with refractory ARDS requiring VV-ECMO.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Hipertrofia Ventricular Direita/diagnóstico por imagem , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Síndrome do Desconforto Respiratório/terapia , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/fisiopatologia , Ecocardiografia , Mortalidade Hospitalar , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertrofia Ventricular Direita/mortalidade , Hipertrofia Ventricular Direita/fisiopatologia , Pessoa de Meia-Idade , Prognóstico , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/fisiopatologia , Estudos Retrospectivos , Disfunção Ventricular Direita/diagnóstico por imagem , Função Ventricular Direita
4.
J Cardiovasc Med (Hagerstown) ; 16(9): 610-5, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25010507

RESUMO

In clinical practice, acidotic patients with acute cardiogenic pulmonary edema (ACPE) are commonly considered more severe in comparison with nonacidotic patients, and data on the outcome of these patients treated with noninvasive pressure support ventilation (NIV) are lacking.The present investigation was aimed at assessing whether acidosis on admission (pH < 7.35) was associated with adverse outcome in 65 consecutive patients with ACPE treated with NIV and admitted to our Intensive Cardiac Care Unit (ICCU).In our population, 28 patients were acidotic (28 of 65, 43.1%), whereas 41 patients were not (37 of 65, 56.9%). According to the Repeated Measures General Linear Model, pCO2 values significantly changed throughout the 2-h NIV treatment (P = 0.019) in both groups (P = 0001). In acidotic patients, pCO2 significantly decreased (51.9 ±â€Š15.3 → 47.0 ±â€Š12.8 → 44.8 ±â€Š12.7), whereas they increased in the nonacidotic subgroup (36.8 ±â€Š6.5 → 36.9 ±â€Š7.2 → 37.6 ±â€Š6.4). No difference was observed in intubation rate between acidotic (eight patients, 28.6%) and nonacidotic patients (12 patients, 32.4%) (P = 0.738). In-ICCU mortality rate did not differ between (13 patients, 35.1%) and nonacidotic patients (nine patients, 32.1%) (P = 0.801).Our data strongly suggest that in patients with severe ACPE treated with NIV, the presence of acidosis is not associated with adverse outcomes (early mortality and intubation rates) in these patients.


Assuntos
Acidose/etiologia , Respiração com Pressão Positiva/métodos , Edema Pulmonar/complicações , Acidose/sangue , Acidose/fisiopatologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Dióxido de Carbono/sangue , Comorbidade , Unidades de Cuidados Coronarianos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ventilação não Invasiva/métodos , Oxigênio/sangue , Pressão Parcial , Edema Pulmonar/fisiopatologia , Edema Pulmonar/terapia , Resultado do Tratamento
5.
Eur Heart J Acute Cardiovasc Care ; 2(2): 118-26, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24222820

RESUMO

Guidelines stated that extracorporeal membrane oxygenation (ECMO) may improve outcomes after refractory cardiac arrest (CA) in cases of cardiogenic shock and witnessed arrest, where there is an underlying circulatory disease amenable to immediate corrective intervention. Due to the lack of randomized trials, available data are supported by small series and observational studies, being therefore characterized by heterogeneity and controversial results. In clinical practice, using ECMO involves quite a challenging medical decision in a setting where the patient is extremely vulnerable and completely dependent on the medical team's judgment. The present review focuses on examining existing evidence concerning inclusion and exclusion criteria, and outcomes (in-hospital and long-term mortality rates and neurological recovery) in studies performed in patients with refractory CA treated with ECMO. Discrepancies can be related to heterogeneity in study population, to differences in local health system organization in respect of the management of patients with CA, as well as to the fact that most investigations are retrospective. In the real world, patient selection occurs individually within each center based on their previous experience and expertise with a specific patient population and disease spectrum. Available evidence strongly suggests that in CA patients, ECMO is a highly costly intervention and optimal utilization requires a dedicated local health-care organization and expertise in the field (both for the technical implementation of the device and for the intensive care management of these patients). A careful selection of patients guarantees optimal utilization of resources and a better outcome.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Parada Cardíaca/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Reanimação Cardiopulmonar/métodos , Criança , Hospitalização , Humanos , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/terapia , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
6.
Eur J Clin Invest ; 43(5): 429-38, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23480577

RESUMO

BACKGROUND: Growing evidence was collected that non-alcoholic liver fatty disease (NAFLD) is a risk factor for coronary atherosclerosis in terms of angiographic appearance, but its involvement in acute coronary syndromes is still debated. We investigated the prevalence and severity of NAFLD in non-diabetic patients admitted for ST-segment elevation myocardial infarction (STEMI) and its association with multi-vessel coronary artery disease (CAD). MATERIALS AND METHODS: Ninety-five consecutive non-diabetic patients admitted to cardiac ICU for STEMI were studied by ultrasound within 72 h from admission. NAFLD was graded according to a semi-quantitative severity score as mild (score < 3) or moderate-severe (> 3 score). Prevalence of cardiovascular (CV) risk factors, atherosclerotic burden markers and metabolic syndrome (MS) was investigated. RESULTS: The overall prevalence of NAFLD was 87%. Forty-eight patients showed moderate-severe NAFLD (SFLD). Thirty-five patients showed mild NAFLD (MLFD group) and 12 patients had no NAFLD. Patients with SFLD were younger and showed higher prevalence of multi-vessel CAD (i.e. > 2) than patients with mild MFLD (P < 0·01). Total cholesterol, triglycerides, body mass index and waist circumference were higher and HDL lower in SFLD than MFLD patients. About 50% of all NAFLD patients did not have MS. MS prevalence was higher in SFLD than MLFD patients (P < 0·05) and among MS components, waist circumference and triglyceride levels showed the strongest association with SFLD (P < 0·05). At logistic regression analysis, SFLD was independently associated with a three-fold risk of multi-vessel CAD. CONCLUSIONS: In non-diabetic patients admitted for STEMI NAFLD prevalence was very high. Severe NAFLD independently increased the risk for multi-vessel CAD associated to CV events.


Assuntos
Síndrome Coronariana Aguda/complicações , Fígado Gorduroso/complicações , Síndrome Metabólica/complicações , Síndrome Coronariana Aguda/diagnóstico por imagem , Idoso , Doença da Artéria Coronariana/etiologia , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico por imagem , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Fatores de Risco , Índice de Gravidade de Doença , Ultrassonografia
7.
Eur J Clin Invest ; 42(9): 927-32, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22463054

RESUMO

BACKGROUND: To assess the effect of a personalized physical activity programme on weight and circulating (CPC) and endothelial progenitor cells (EPC) in overweight and obese subjects. MATERIALS AND METHODS: Anthropometric measurements with body composition, cardiopulmonary test, maximal stress exercise test with maximal oxygen uptake (VO(2max) ) and a series of biochemical analyses were taken before (T0) and after 3 months of physical activity (T1) in a total of 80 overweight and obese subjects. CPC and EPC were determined using flow cytometry and were defined as CD34+, CD133+ and CD34+/CD133+ for CPC and CD34+KDR+, CD133+KDR+ and CD34+CD133+KDR+ for EPC. RESULTS: At the end of the programme, we divided the population into two groups, compliant individuals (group A, n = 47) and noncompliant individuals (group B, n = 33). Group A reported significant reductions of weight by 3·1% (P < 0·0001) and fat mass by 4·4% (P < 0·0001), while group B showed a percentage of increase in fat mass by 1·5% at T1. In group A, a trend of increase at T1 for circulating levels of CPC and EPC was observed, reaching the statistical significance for all the three types of EPC. On the contrary, group B showed no significant increase in CPC and EPC. Furthermore, a significant correlation between decrease in fat mass and increase in CD133+/KDR+ EPC was reported in group A (r = 0·50; P = 0·04). CONCLUSION: Three months of physical activity significantly improved anthropometric measurements. A beneficial effect of increased number of EPC in compliant individuals, in relation to weight loss, was observed.


Assuntos
Células Endoteliais/fisiologia , Exercício Físico/fisiologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Células-Tronco/fisiologia , Adulto , Idoso , Antígenos CD34/metabolismo , Composição Corporal , Teste de Esforço/métodos , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Tempo , Adulto Jovem
8.
Congest Heart Fail ; 18(1): 47-53, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22277178

RESUMO

A pivotal role in treating decompensated heart failure (HF) is played by inotropes and calcium sensitizers such as levosimendan. In this study, the authors evaluated whether levosimendan could determine further clinical and hemodynamic benefits in 31 HF patients (New York Heart Association [NYHA] class III or IV), after successful treatment with diuretics (n=15) or ultrafiltration (n=16). Systolic, diastolic, dicrotic, and mean arterial pressures; systemic vascular resistance (SVR); some classic hemodynamic variables (cardiac output [CO], stroke volume [SV], dP/dt(max) ); and indices of cardiovascular system performance (cardiac cycle efficiency [CCE], cardiac power output) have been assessed by the pressure recording analytical method (PRAM), a minimally invasive monitoring system, before levosimendan infusion, at the end of treatment (EoT), and 36 hours after EoT (post-36). A significant increase in CCE, CO, SV, and dP/dt(max) and a significant decrease in diastolic and dicrotic arterial pressures and in SVR have been observed at EoT and at post-36. After the addition of levosimendan, a further reduction in signs and symptoms of HF and NYHA class was observed. Five patients showed an opposite trend of several hemodynamic parameters without any significant clinical improvement (nonresponders). In conclusion, most HF patients treated with diuretics or ultrafiltration receive additional clinical and hemodynamic benefits from levosimendan. The characterization of nonresponders could help in optimizing its use.


Assuntos
Líquidos Corporais , Cardiotônicos/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Hidrazonas/administração & dosagem , Piridazinas/administração & dosagem , Idoso , Pressão Sanguínea , Débito Cardíaco , Feminino , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Humanos , Masculino , Monitorização Fisiológica , Estudos Prospectivos , Simendana , Resultado do Tratamento
9.
J Cardiovasc Med (Hagerstown) ; 11(10): 748-53, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20479654

RESUMO

OBJECTIVES: Previous investigations on microalbuminuria in acute myocardial infarction have been performed in heterogeneous populations of hypetensive/nonhypertensive, diabetic/nondiabetic patients, submitted to either thrombolysis or mechanical revascularization or not revascularized. Therefore, the aim of our investigation was to assess, in 242 consecutive hypertensive patients with ST elevation myocardial infarction without previously known diabetes, all submitted to mechanical revascularization, whether microalbuminuria, in the early phase, has a prognostic role for in-hospital mortality or complications (acute pulmonary edema and arrhythmias). METHODS: The study population was divided into two groups according to microalbuminuria excretion: group A (microalbuminuria within the normal range); group B (microalbuminuria above the normal range). RESULTS: The incidence of microalbuminuria was 52.1% (126/242). No significant difference was detectable in the incidence of in-hospital mortality and complications between the two groups. Patients with microalbuminuria exhibit a larger infarct size as indicated by higher values of troponin I. Microalbuminuria was associated with higher values of glucose and a higher prevalence of insulin resistance. CONCLUSION: In ST elevation myocardial infarction hypertensive patients without previously known diabetes, all submitted to mechanical revascularization, microalbuminuria is a common finding but it does not yield prognostic information about in-hospital mortality or complications. Interestingly it was associated with acute glucose dysmetabolism (as inferred by hyperglycemia and the prevalence of insulin resistance), thus suggesting that it can be considered part of the acute metabolic response to the acute coronary event.


Assuntos
Albuminúria/epidemiologia , Angioplastia Coronária com Balão , Hipertensão/epidemiologia , Infarto do Miocárdio/terapia , Idoso , Idoso de 80 Anos ou mais , Albuminúria/mortalidade , Albuminúria/urina , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/mortalidade , Arritmias Cardíacas/epidemiologia , Glicemia/metabolismo , Distribuição de Qui-Quadrado , Feminino , Mortalidade Hospitalar , Humanos , Hiperglicemia/epidemiologia , Hipertensão/mortalidade , Hipertensão/urina , Incidência , Resistência à Insulina , Itália/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/urina , Edema Pulmonar/epidemiologia , Medição de Risco , Fatores de Risco , Resultado do Tratamento
10.
J Hypertens ; 28(5): 910-7, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20139769

RESUMO

BACKGROUND: Guidelines recommend that blood pressure (BP) should be lowered in hypertensive patients to prevent cardiovascular accidents. Management of antihypertensive treatment by general practitioners is usually based on office measurements, which may not allow an assessment of BP control over 24 h, which requires ambulatory BP monitoring (ABPM) to be implemented. This is rarely done in general practice, and limited information is available on the consistency between the evaluations of the response to treatment provided by office measurement and by ABPM in this setting. AIM: To assess concordance between office BP measurements and ABPM-based estimates of hypertension control in a general practice setting. DESIGN OF STUDY: Prospective, comparative between techniques. SETTING: General practice. METHODS: Seventy-eight general practices, representative of all Italian regions, participated in this study by recruiting sequential hypertensive adults on stabilized treatment, who were subdivided into even groups with office BP, respectively, controlled or noncontrolled by treatment. In each individual, ABPM was applied by the general practitioner after appropriate training, and 24-h ABP values were defined as controlled or not according to current guidelines. Concordance between office and ABPM evaluation of BP control was assessed with kappa statistics. Positive and negative predictive values of office measurement versus ABPM were estimated. RESULTS: Between July 2005 and November 2006, 190 general practitioners recruited 2059 hypertensive patients based on office BP measurements; in 1728 patients, a 24-h ABPM was performed, yielding 1524 recordings considered as valid for further analysis. The agreement between the assessment of BP control by office measurement and by ABPM was poor (kappa = 0.120), with office measurements showing a satisfactory positive predictive value (0.842) and a poor negative predictive value (0.278); the situation was worse in patients with three or more among the following features: male sex, age of at least 65 years, alcohol consumption, diabetes, and obesity (negative predictive value = 0.149). CONCLUSION: In general practice, the agreement between assessment of BP control by treatment provided by office and ambulatory BP measurements is better in patients of 'uncontrolled' office BP than in 'controlled' office BP patients. This emphasizes the need for the larger use of out-of-office BP monitoring in a general practice setting, in particular, in patients considered as 'controlled' during consultation.


Assuntos
Determinação da Pressão Arterial , Monitorização Ambulatorial da Pressão Arterial , Hipertensão/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Medicina de Família e Comunidade , Feminino , Humanos , Hipertensão/tratamento farmacológico , Itália , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Adulto Jovem
11.
Am J Hypertens ; 21(7): 748-52, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18443565

RESUMO

BACKGROUND: Higher blood pressure (BP) values in cold than in hot months has been documented in hypertensives. These changes may potentially contribute to the observed excess winter cardiovascular mortality. However, the association with weather has always been investigated by considering the relationship with a single variable rather than considering the combination of ground weather variables characterizing a specific weather pattern (air mass (AM)). METHODS: We retrospectively investigate in Florence (Italy) the relationship between BP and specific AMs in hypertensive subjects (n = 540) referred to our Hypertension Unit for 24-h ambulatory BP monitoring during the period of the year characterized by the highest weather variability (winter). Five different winter daily AMs were classified according to the combination of ground weather data (air temperature, cloud cover, relative humidity, atmospheric pressure, wind speed, and direction). RESULTS: Multiple variable analysis selected the AM as a significant predictor of mean 24-h BP (P < 0.01 for diastolic BP (DBP) and P < 0.05 for systolic BP (SBP)), daytime DBP (P < 0.001) and nighttime BP (P < 0.01 for both SBP and DBP), with higher BP values observed in cyclonic (unstable, cloudy, and mild weather) than in anticyclonic (settled, cloudless, and cold weather) days. When the association with 2-day sequences of AMs was considered, an increase in ambulatory BP followed a sudden day-to-day change of weather pattern going from anticyclonic to cyclonic days. CONCLUSIONS: The weather considered as a combination of different weather variables may affect BP. The forecast of a sudden change of AM could provide important information helpful for hypertensives during winter.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Ritmo Circadiano , Hipertensão/fisiopatologia , Estações do Ano , Tempo (Meteorologia) , Adulto , Idoso , Feminino , Frequência Cardíaca , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Am J Phys Med Rehabil ; 87(1): 46-52; quiz 53-6, 83, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18158430

RESUMO

OBJECTIVE: The 6-min walk test (6mWT) is widely used to assess physical performance in cardiac rehabilitation settings. Factors affecting the walked distance before starting physical training have been described, whereas information on factors affecting the increase of the walked distance after physical training is still scant. The aim of this study was to verify, in a large sample of elderly patients soon after cardiac surgery, the role of left-ventricular function (LVF) in increases in distances walked after an intensive rehabilitation program. DESIGN: We enrolled 459 patients (300 males and 159 females, mean [+/-SD] age 70 +/- 11 yrs). According to the echographic ejection fraction, patients were classed into two categories, LVF > or = 40% and LVF < 40%. All patients performed the 6mWT at the beginning and end of the rehabilitation program. RESULTS: Longer walked distances before and after the rehabilitation program were significantly associated with preserved or moderately depressed LVF, whereas greater relative increases of the distance walked after the rehabilitation program were significantly associated with poor LVF (P < 0.001 for all). CONCLUSIONS: Among elderly patients admitted as inpatients to an intensive rehabilitation program soon after cardiac surgery, those with poor LVF are most likely to respond more favorably to physical training. Therefore, instead of considering poor LVF a risk for starting physical training in these patients, it should be considered a strong indication, to avoid further physical deconditioning and disability.


Assuntos
Procedimentos Cirúrgicos Cardíacos/reabilitação , Teste de Esforço/métodos , Tolerância ao Exercício/fisiologia , Disfunção Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Função Ventricular Esquerda , Caminhada
13.
Diabetes ; 54(2): 394-401, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15677497

RESUMO

Hyperglycemia was reported to enhance angiotensin (Ang) II generation in rat cardiomyocytes, and Ang II inhibition reduces cardiovascular morbidity and mortality in diabetic patients. In diabetic patients, the enhanced activation of intracellular pathways related with myocyte hypertrophy and gene expression might enhance the progression of cardiac damage. Therefore, we investigated the effects of glucose on Ang II-mediated activation of Janus-activated kinase (JAK)-2, a tyrosine kinase related with myocyte hypertrophy and cytokine and fibrogenetic growth factor overexpression, in ventricular myocytes isolated from nonfailing human hearts (n = 5) and failing human hearts (n = 8). In nonfailing myocytes, JAK2 phosphorylation was enhanced by Ang II only in the presence of high glucose (25 mmol/l) via Ang II type I (AT1) receptors (+79% vs. normal glucose, P < 0.05). JAK2 activation was prevented by inhibitors of reactive oxygen species (ROS) generation (diphenyleneiodonium [DPI], tiron, and apocynin). In myocytes isolated from failing hearts, JAK2 phosphorylation was enhanced by high glucose alone (+107%, P < 0.05). High glucose-induced JAK2 activation was blunted by both ACE inhibition (100 nmol/l ramipril) and AT1 antagonism (1 mumol/l valsartan), thus revealing that the effects are mediated by autocrine Ang II production. Inhibition of ROS generation also prevented high glucose-induced JAK2 phosphorylation. In conclusion, in human nonfailing myocytes, high glucose allows Ang II to activate JAK2 signaling, whereas in failing myocytes, hyperglycemia alone is able to induce Ang II generation, which in turn activates JAK2 via enhanced oxidative stress.


Assuntos
Angiotensina II/farmacologia , Coração/fisiologia , Células Musculares/fisiologia , Estresse Oxidativo/fisiologia , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais/fisiologia , Animais , Feminino , Coração/efeitos dos fármacos , Insuficiência Cardíaca/fisiopatologia , Humanos , Janus Quinase 2 , Cinética , Masculino , Pessoa de Meia-Idade , Células Musculares/efeitos dos fármacos , Fosforilação , Proteínas Tirosina Quinases/efeitos dos fármacos , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos , Doadores de Tecidos
14.
Crit Care Med ; 32(5): 1170-7, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15190969

RESUMO

OBJECTIVE: To investigate whether an inflammatory response occurs in patients undergoing infrarenal aortic abdominal aneurysm repair, the localization and timing (ischemia and/or reperfusion) of this activation, and finally whether it affects postoperative pulmonary function. DESIGN: Prospective, observational study. SETTING: Academic referral center in Italy. PATIENTS: We included 12 patients undergoing infrarenal aortic abdominal aneurysm repair and 12 patients undergoing major abdominal surgery. INTERVENTIONS: Timed measurement of gene activation (angiotensinogen, angiotensin type 1 receptor, angiotensin-converting enzyme, and interleukin-6 genes) in muscle biopsies by reverse transcriptase-polymerase chain reaction (RT-PCR), and prospective assessment of interleukin-6 plasma concentration and pulmonary function (Pao2/FIO2 and Pao2/PAO2 ratios). MEASUREMENTS AND MAIN RESULTS: After 30 mins of aortic clamping, angiotensinogen, angiotensin type 1 receptor, angiotensin-converting enzyme, and interleukin-6 genes were all overexpressed at RT-PCR studies in quadriceps muscle of patients undergoing aortic abdominal aneurysm repair, and the overexpression persisted after reperfusion. In situ hybridization and immunohistochemistry revealed that the inflammatory response was localized in endothelial cells. A significant increase in plasma interleukin-6 concentrations was then detectable at 6 and 12 hrs after reperfusion in aortic abdominal aneurysm surgery compared with patients undergoing abdominal surgery (p < .05). The increase in interleukin-6 plasma concentration was then followed (12 and 24 hrs after surgery) by a significant reduction of Pao2/ FIO2 and Pao2/PAO2 ratios (p < .05 vs. abdominal surgery). CONCLUSIONS: The present study shows that a) during aortic surgery, the genes for interleukin-6 and for the components of the local renin-angiotensin system (angiotensinogen, angiotensin-converting enzyme, and angiotensin type 1 receptor subtype) are activated early in the ischemic muscle, and activation persists during reperfusion; b) interleukin-6 plasma concentration increases only in patients with tissue ischemia (aortic abdominal aneurysm), whereas no changes are detectable in patients with abdominal surgery; and finally c) the occurrence of systemic inflammatory reaction with increased interleukin-6 plasma concentrations is followed by impaired pulmonary function.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Pneumopatias/etiologia , Complicações Pós-Operatórias/etiologia , Traumatismo por Reperfusão/etiologia , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Idoso , Angiotensinogênio/análise , Angiotensinogênio/fisiologia , Colectomia/efeitos adversos , Feminino , Gastrectomia/efeitos adversos , Regulação da Expressão Gênica/fisiologia , Humanos , Inflamação , Interleucina-6/análise , Interleucina-6/fisiologia , Pneumopatias/diagnóstico , Pneumopatias/metabolismo , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/química , Músculo Esquelético/patologia , Nefrectomia/efeitos adversos , Peptidil Dipeptidase A/análise , Peptidil Dipeptidase A/fisiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/metabolismo , Estudos Prospectivos , Receptor Tipo 1 de Angiotensina/análise , Receptor Tipo 1 de Angiotensina/fisiologia , Sistema Renina-Angiotensina/fisiologia , Traumatismo por Reperfusão/diagnóstico , Traumatismo por Reperfusão/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Coxa da Perna/irrigação sanguínea , Ativação Transcricional , Resultado do Tratamento
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