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1.
Clin Res Cardiol ; 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38117299

RESUMO

BACKGROUND: Anxiety and limited patient comprehension may pose significant barriers when informing elderly patients about complex procedures such as transcatheter aortic valve implantation (TAVI). OBJECTIVES: We aimed to evaluate the utility of medical graphics to improve the patient informed consent (IC) before TAVI. METHODS: In this prospective, randomized dual center study, 301 patients were assigned to a patient brochure containing medical graphics (Comic group, n = 153) or sham information (Control group, n = 148) on top of usual IC. Primary outcomes were patient understanding of central IC-related aspects and periprocedural anxiety assessed by the validated Spielberger State Trait Anxiety Inventory (STAI), both analyzed by cognitive status according to the Montreal Cognitive Assessment (MoCA). RESULTS: Patient understanding was significantly higher in the Comic group [mean number of correct answers 12.8 (SD 1.2) vs. 11.3 (1.8); mean difference 1.5 (95% CI 1.2-1.8); p < 0.001]. This effect was more pronounced in the presence of cognitive dysfunction (MoCA < 26) [12.6 (1.2) in the Comic vs. 10.9 (1.6) in the Control group; mean difference 1.8 (1.4-2.2), p < 0.001]. Mean STAI score declined by 5.7 (95% CI 5.1-6.3; p < 0.001) in the Comic and 0.8 points (0.2-1.4; p = 0.015) in the Control group. Finally, mean STAI score decreased in the Comic group by 4.7 (3.8-5.6) in cognitively impaired patients and by 6.6 (95% CI 5.8 to 7.5) in patients with normal cognitive function (p < 0.001 each). CONCLUSIONS: Our results prove beneficial effects for using medical graphics to inform elderly patients about TAVI by improving patient understanding and reducing periprocedural anxiety (DRKS00021661; 23/Oct/2020). Medical graphics entailed significant beneficial effects on the primary endpoints, patient understanding and periprocedural anxiety, compared to the usual patient informed consent (IC) procedure. Patient understanding of IC-related aspects was significantly higher in the Comic group, with a more pronounced benefit in patients with cognitive impairment (p for IC method and cognitive status < 0.001, respectively; p for IC method x MoCA category interaction = 0.017). There further was a significant decline of periprocedural anxiety in patients with and without cognitive impairment (p for IC method x measuring time point < 0.001; p for IC method x MoCA category x measuring time point interaction = 0.018).

2.
Int J Cardiol Heart Vasc ; 41: 101076, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35800041

RESUMO

Background: Patients scheduled for coronary angiography may feel insufficiently informed about the planned procedure. We aimed to evaluate the patient-rated quality of the Informed Consent (IC) process and to investigate the efficacy of medical graphics to assist and improve the IC procedure. Methods: A graphic-based information broschure illustrating central steps of the procedure was created in collaboration with scientific illustrators. In a randomized, controlled, prospective trial, 121 patients undergoing coronary angiography/PCI were randomized to a group obtaining the usual IC (Control group) or to a group that additionally obtained a graphic-based IC (Comic group). The perceived quality of the IC was compared between groups using single items of the Client Satisfaction Questionnaire-8 and self-designed single items. Results: Only 67.8% of patients stated to have completely read the standard written IC sheet. The quality of the IC was perceived to be very good in 45.0% of patients in the Comic group compared to 24.6% in the Control group (p =.023). 57.4% of the Control group compared to 76.7% of the Comic group stated that all of their questions were satisfactorily adressed (p =.015). 43.3% of the Comic group, in contrast to only 18.0% of the Control group, declared to feel "very satisfied" with the obtained IC procedure (p =.002). The acceptance of this new IC approach was very high: no patient expressed feelings of not being taken seriously when reading medical graphics. Conclusions: Our data confirm pronounced limitations of the usual IC practice. The use of medical graphics positively impacts on patient-evaluated endpoints and may significantly improve the IC procedure.

3.
Br J Cancer ; 111(8): 1526-31, 2014 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-25117808

RESUMO

BACKGROUND: Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC). METHODS: Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months. RESULTS: Median pretherapeutic serum GGT level was 25 U l(-1). Gamma-glutamyltransferase levels increased with advancing T (P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l(-1) was associated with an increase in the risk of death from RCC by 4% (HR 1.04, P<0.001). Based on recursive partitioning-based survival tree analysis, we defined four prognostic categories of GGT: normal low (<17.5 U l(-1)), normal high (17.5 to <34.5 U l(-1)), elevated (34.5 to <181.5 U l(-1)), and highly elevated (⩾181.5 U l(-1)). In multivariable analyses that adjusted for the effect of standard features, both continuously and categorically coded GGT were independent prognostic factors. Adding GGT to a model that included standard features increased the discrimination by 0.9% to 1.8% and improved the clinical net benefit. CONCLUSIONS: Pretherapeutic serum GGT is a novel and independent prognostic factor for patients with RCC. Stratifying patients into prognostic subgroups according to GGT may be used for patient counselling, tailoring surveillance, individualised treatment planning, and clinical trial design.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/enzimologia , Neoplasias Renais/enzimologia , gama-Glutamiltransferase/sangue , Idoso , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
4.
Exp Clin Endocrinol Diabetes ; 119(6): 353-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21472666

RESUMO

Proinflammatory cell activation via the receptor for advanced glycation end products (RAGE) pathway may play a central pathogenetic role in atherosclerosis. Since S100A8/A9 was recently identified as ligand of RAGE, we determined the effects of proinflammatory cytokines on RAGE-mediated induction of gene expression of S100A8 and S100A9. mRNA levels of S100A8 and S100A9 were upregulated following cytokine stimulation with IL-6 (1, 10, 100 ng/ml) or TNFα (10 ng/ml) in human THP-1 cells. Preincubation of cells with 2000 ng/ml AGE (advanced glycation end products) before cytokine stimulation resulted in upregulation of RAGE. Pretreatment of THP-1 with AGE followed by stimulation with IL-6 (10 ng/ml) or TNFα (10 ng/ml) further increased S100A8 and S100A9 mRNA expression and S100A8/A9 release into cell culture supernatant, as compared to pretreatment with non-glycated albumin as control. Binding of AGE to RAGE was blocked with a neutralizing anti-RAGE antibody. Normal mouse IgG served as control. Cytokine-stimulated induction of S100A8 and S100A9 mRNA levels as well as of S100A8/A9 release after preincubation of cells with AGE were significantly suppressed by RAGE blockade, indicating a RAGE-dependent pathway of AGE-mediated S100A8/A9 expression.The cytokine-induced potentiated S100A8 and S100A9 expression under conditions with a high AGE burden is able to aggravate proinflammatory conditions via activation of the RAGE pathway.


Assuntos
Calgranulina A/genética , Calgranulina B/genética , Leucemia/patologia , Receptores Imunológicos/fisiologia , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Calgranulina A/metabolismo , Calgranulina B/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/farmacologia , Leucemia/genética , Leucemia/metabolismo , Camundongos , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fator de Necrose Tumoral alfa/farmacologia
5.
Cardiology ; 113(3): 222-30, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19246898

RESUMO

OBJECTIVES: This report focuses on the design and methods of the 3-centre clinical study of the Transregional Collaborative Research Centre 'Inflammatory Cardiomyopathy--Molecular Pathogenesis and Therapy', which aims to establish a comprehensive research registry on the diagnostics, therapy and disease outcomes of patients with inflammatory cardiomyopathy (CMi). The study goals are to investigate specific disease sub-entities and to develop standardised strategies for diagnostics and treatment. METHODS: All consecutive patients with clinically suspected CMi, post-myocarditic cardiomyopathy and acute myocarditis are included in the research registry. Cardiopulmonary functional tests, clinical and patient data are obtained at baseline and subsequent readmission appointments and are linked to allow for prospective follow-up. Co-morbidities, quality of life, health- related behaviour and sociodemographic variables are ascertained using uniform self-administered questionnaires. PRESENT STATUS: By May 2008, 2,061 cases had been included in the research registry (1,300 data-sets completed). At registration, 335 patients were diagnosed with CMi. The mean age was 50 +/- 13 years and the mean ejection fraction was 39.9 +/- 15.8%. CONCLUSIONS: The broad range of the acquired molecular-biological, histological, immunohistological, clinical and patient data makes this the most comprehensive research registry on patients with CMi to date.


Assuntos
Cardiomiopatias , Miocardite , Doença Aguda , Adulto , Idoso , Cardiomegalia/epidemiologia , Cardiomiopatias/diagnóstico , Cardiomiopatias/epidemiologia , Cardiomiopatias/terapia , Comorbidade , Comportamento Cooperativo , Feminino , Seguimentos , Doenças Genéticas Inatas/epidemiologia , Alemanha , Comportamentos Relacionados com a Saúde , Humanos , Infecções/epidemiologia , Masculino , Pessoa de Meia-Idade , Miocardite/diagnóstico , Miocardite/epidemiologia , Miocardite/terapia , Prognóstico , Qualidade de Vida , Sistema de Registros , Fatores de Risco , Fatores Socioeconômicos
6.
Pneumologie ; 61(11): 700-8, 2007 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-17929214

RESUMO

Acute heart failure syndromes (AHFS) are a growing health problem in Western Countries. Standard treatment includes vasodilators and diuretics, however, the subgroup of patients with AHFS and low cardiac output state represents a special therapeutic challenge that is complicated by high in-hospital and post-discharge mortality and by requiring additional i. v. inotropic support. The current inotropes in use are adrenoreceptor agonists (dopamine, dobutamine, norepinephrine, epinephrine), phosphodiesterase III inhibitors (milrinone, enoximone), and Ca2+ sensitizers (levosimendane). While most inotropes yield short-term haemodynamic improvements, they are associated with increased myocardial oxygen consumption, (supra-) ventricular arrhythmias and possibly increased post-discharge mortality. This review highlights current inotropes used in the treatment of AHFS and introduces new drug developments including myosin activators and Na+/K+ ATPase inhibitors.


Assuntos
Baixo Débito Cardíaco/tratamento farmacológico , Cardiotônicos/uso terapêutico , Catecolaminas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Doença Aguda , Baixo Débito Cardíaco/epidemiologia , Cardiotônicos/efeitos adversos , Catecolaminas/efeitos adversos , Estudos Transversais , Insuficiência Cardíaca/epidemiologia , Hemodinâmica/efeitos dos fármacos , Humanos , Miocárdio/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
8.
Europace ; 8(1): 70-5, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16627413

RESUMO

AIMS: We prospectively evaluated results from cardiopulmonary exercise testing for chronotropic incompetence (CI) in a cohort of 292 pacemaker patients. In addition, we evaluated comorbidity and antiarrhythmic patient data as indicators of CI. METHODS AND RESULTS: On the basis of exercise stress testing and application of the definition of CI by Wilkoff, 51% of our cohort was categorized as having CI. Indications for pacemaker implant for this patient group were 42% atrioventricular block, 56% sinus node disease, and 59% atrial fibrillation. Maximum oxygen uptake (VO(2) max) and exercise duration were significantly reduced among CI pacemaker patients, whereas oxygen uptake at the anaerobic threshold remained unchanged. The following clinical characteristics were significant predictors of CI: existence of coronary artery disease (P = 0.038), presence of an acquired valvular heart disease (P = 0.037), and former cardiac surgery (P = 0.041). Age, gender, arterial hypertension, cardiomyopathy, congenital heart disease, left ventricular ejection fraction, and time period between stress-exercise examination and pacemaker implantation were not significant predictors of CI. Chronic antiarrhythmic therapy with digitalis (P = 0.013), beta blockers (P = 0.036), and amiodarone (P = 0.045) were significant predictors of CI. In contrast, medication with class I and IV antiarrhythmics had no significant correlation with CI. CONCLUSION: We found the following characteristics predictive of CI in this pacemaker patient population: VO(2) max, existence of coronary artery disease or acquired valvular heart disease, previous cardiac surgery, as well as medication with digitalis, beta blockers, and amiodarone.


Assuntos
Marca-Passo Artificial , Nó Sinoatrial/fisiopatologia , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/terapia , Comorbidade , Teste de Esforço , Feminino , Bloqueio Cardíaco/fisiopatologia , Bloqueio Cardíaco/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Resistência Física , Valor Preditivo dos Testes , Estudos Prospectivos , Análise de Regressão , Síndrome do Nó Sinusal/fisiopatologia , Síndrome do Nó Sinusal/terapia
9.
Oncogene ; 25(20): 2890-900, 2006 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-16407844

RESUMO

The balance between hematopoietic progenitor commitment and self-renewal versus differentiation is controlled by various transcriptional regulators cooperating with cytokine receptors. Disruption of this balance is increasingly recognized as important in the development of leukemia, by causing enhanced renewal and differentiation arrest. We studied regulation of renewal versus differentiation in primary murine erythroid progenitors that require cooperation of erythropoietin receptor (EpoR), the receptor tyrosine kinase c-Kit and a transcriptional regulator (glucocorticoid receptor; GR) for sustained renewal. However, mice defective for GR- (GR(dim/dim)), EpoR- (EpoR(H)) or STAT5ab function (Stat5ab(-/-)) show no severe erythropoiesis defects in vivo. Using primary erythroblast cultures from these mutants, we present genetic evidence that functional GR, EpoR, and Stat5 are essential for erythroblast renewal in vitro. Cells from GR(dim/dim), EpoR(H), and Stat5ab(-/-) mice showed enhanced differentiation instead of renewal, causing accumulation of mature cells and gradual proliferation arrest. Stat5ab was additionally required for Epo-induced terminal differentiation: differentiating Stat5ab(-/-) erythroblasts underwent apoptosis instead of erythrocyte maturation, due to absent induction of the antiapoptotic protein Bcl-X(L). This defect could be fully rescued by exogenous Bcl-X(L). These data suggest that signaling molecules driving leukemic proliferation may also be essential for prolonged self-renewal of normal erythroid progenitors.


Assuntos
Diferenciação Celular , Proliferação de Células , Células Precursoras Eritroides/metabolismo , Receptores da Eritropoetina/fisiologia , Receptores de Glucocorticoides/fisiologia , Fator de Transcrição STAT5/fisiologia , Animais , Apoptose , Western Blotting , Células Cultivadas , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Eritroblastos/citologia , Eritroblastos/metabolismo , Citometria de Fluxo , Humanos , Fígado/citologia , Fígado/metabolismo , Camundongos , Proteína bcl-X/genética , Proteína bcl-X/metabolismo
11.
Cell Mol Life Sci ; 60(4): 688-700, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12785716

RESUMO

The peptide relaxin has long been regarded as an important hormone of pregnancy, contributing to changes in connective tissue composition as well as to regulation of implantation, myometrial activity and labor. On the other hand, the astonishing pleiotropy of this hormone escaped scientific awareness. This review focuses on new facets of relaxin, including its antifibrotic effects, its role in the control of pituitary hormone release, its vasodilator and pro-angiogenic properties and its versatile myocardial actions. Recent progress in understanding relaxin's receptor and signaling mechanisms is also highlighted. The peptide will be characterized as potential regulator of body fluid and circulation homeostasis.


Assuntos
Líquidos Corporais/fisiologia , Homeostase/fisiologia , Relaxina/fisiologia , Circulação Sanguínea/fisiologia , Encéfalo/fisiologia , Tecido Conjuntivo/fisiologia , Feminino , Expressão Gênica/fisiologia , Genitália Feminina/fisiologia , Coração/fisiologia , Humanos , Rim/fisiologia , Especificidade de Órgãos , Receptores Acoplados a Proteínas G , Receptores de Peptídeos , Relaxina/genética , Transdução de Sinais
12.
Acta Anaesthesiol Scand ; 47(6): 667-74, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12803583

RESUMO

BACKGROUND: During conventional cardiac surgery ischemia and reperfusion may cause excessive production of reactive oxygen species leading to tissue damage including early arrhythmias. We therefore assessed the kinetics of markers of radical stress including oxidized and reduced glutathione (GSSG/GSH), oxidized proteins (PCG) and malondialdehyde (MDA), and tested the hypothesis that different steroid treatments inhibit these markers and early reperfusion-associated supraventricular and ventricular extrasystolic beats. METHODS: In a randomized, controlled, blinded, prospective trial 36 patients received a preoperative infusion of methylprednisolone (MP, 15 mg kg-1, n = 12), tirilazad mesylate (TM, 10 mg kg-1, n = 12) or placebo (PL, NaCl, n = 12). Coronary sinus and arterial blood was drawn at baseline and 2, 5, 15, 30, 60 and 240 min after aortic declamping. Holter-ECG analysis was used to identify arrhythmias. RESULTS: Cardiac GSSG release occurred very early (< 15 min) and was not significantly attenuated by either drug treatment. Cardiac PCG production showed biphasic increases, lasted > 4 h and was significantly reduced only by TM. Cardiac MDA release was short (< 30 min) and significantly reduced by MP and TM. Neither treatment had a significant influence on the early occurrence of ventricular or supraventricular arrhythmias. The number of patients needing cardioversions or defibrillations also were not different. CONCLUSIONS: The results indicate that cardiac production of reactive oxygen species occurs after reperfusion in humans and is not inhibited by steroid treatment. Steroid treatment effectively reduces lipid peroxidation during cardiac surgery but has no influence on arrhythmias.


Assuntos
Anti-Inflamatórios/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/metabolismo , Procedimentos Cirúrgicos Cardíacos , Vasos Coronários/cirurgia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Esteroides/uso terapêutico , Idoso , Anestesia , Arritmias Cardíacas/etiologia , Biomarcadores , Eletrocardiografia Ambulatorial , Feminino , Glutationa/metabolismo , Hemodinâmica/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/sangue , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Pregnatrienos/uso terapêutico , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
14.
Horm Metab Res ; 34(2): 81-6, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11972292

RESUMO

In human heart failure (CHF), adrenomedullin (AM) counteracts vasoconstriction and sodium retention. We investigated circulating levels of proadrenomedullin N-20 peptide (PAMP) and AM, and left ventricular expression of preproAM and calcitonin receptor-like receptor (CRLR) mRNA. Peptide levels were determined from the left ventricle, pulmonary artery, coronary sinus, and antecubital vein in patients demonstrating severe CHF (n = 12; mean +/- SEM cardiac index, 1.9 +/- 0.2 l/min/m(2); pulmonary wedge pressure, 32 +/- 1 mmHg), moderate CHF (n = 11; cardiac index, 2.9 +/- 0.2; pulmonary wedge pressure, 14 +/- 2), and in controls (n = 11). Left ventricular mRNA was quantified using RT-PCR and Southern blot hybridization. Depending on sites of measurement, PAMP and AM in severe CHF were 1.3 - 2.0 and 1.2 - 1.9 times as high as in moderate CHF, and 3.8 - 4.6 and 2.3 - 2.8 times as high as in controls. Only patients with moderate CHF demonstrated pulmonary and coronary net release of both peptides, that is, significant step-ups in concentrations between the pulmonary artery, left ventricle, and coronary sinus. In failing ventricles, preproAM mRNA increased 2.9 times above control, but CRLR mRNA was unchanged. Altogether, the heart and the lungs release AM peptides in moderate CHF. This secretion breaks down in severe CHF: a process that may contribute to and indicate decompensation. Unlike AM, the CRLR is not transcriptionally upregulated in severe CHF.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Pulmão/metabolismo , Miocárdio/metabolismo , Peptídeos/metabolismo , Adrenomedulina , Proteína Semelhante a Receptor de Calcitonina , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Ventrículos do Coração/química , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Nitroprussiato/uso terapêutico , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Precursores de Proteínas/genética , Proteínas , RNA Mensageiro/análise , Receptores da Calcitonina/genética , Vasodilatadores/uso terapêutico
15.
Biochem Biophys Res Commun ; 289(1): 245-51, 2001 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-11708807

RESUMO

We hypothesized that increased pulmonary vascular pressure--one of the characteristics of congestive heart failure--directly regulates pulmonary endothelial vasoconstrictors (endothelin-1, urotensin II) and vasodilators (adrenomedullin, relaxin). To this end, we subjected pulmonary artery endothelial cells in a novel flow-chamber model to different shear stresses (17, 29, and 46 dyn/cm(2)) at low and elevated levels of downstream pressure (10 and 30 mm Hg). Application of elevated pressure over 16 h increased gene expression and peptide secretion of endothelin-1 at all shear levels, whereas secretion of adrenomedullin rose via decreased expression of its clearance receptor. In contrast, preprourotensin II mRNA and urotensin II peptide decreased in response to elevated pressure, and relaxin remained unaffected. This is the first study to identify pressure as key regulator of mediator synthesis by pulmonary vascular endothelium. Pressure-induced mediator regulation may represent an early event in the development of secondary pulmonary hypertension.


Assuntos
Endotelina-1/fisiologia , Peptídeos/fisiologia , Artéria Pulmonar/fisiologia , Relaxina/fisiologia , Urotensinas/fisiologia , Adrenomedulina , Animais , Bovinos , Células Cultivadas , Endotelina-1/genética , Endotélio Vascular/fisiologia , Expressão Gênica , Hemodinâmica , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Modelos Cardiovasculares , Peptídeos/genética , Pressão , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Adrenomedulina , Receptores de Peptídeos/antagonistas & inibidores , Receptores de Peptídeos/fisiologia , Relaxina/genética , Urotensinas/genética , Vasoconstrição/fisiologia
16.
Biotechnol Prog ; 17(5): 929-34, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11587586

RESUMO

The contractile cycle of the cardiac myocyte is essentially controlled by the concentration of intracellular calcium ([Ca2+]i). Measurement of [Ca2+]i using Ca2+-dependent fluorescence and simultaneous monitoring of cell dynamics enable characterization of a variety of substances interacting with ion channels and contractile proteins. In this report we describe a novel method featuring up to 480 frames/s for monitoring rapid changes in cellular calcium and cell length, in which every individual cycle allows effective evaluation of major cell parameters. Computers aid in determination of time to peak (in ms), time to 50% decrease (ms), diastolic Ca2+ (relative fluorescence units, rfu), systolic Ca2+ (rfu), Ca2+ transients (rfu), DeltaCa2+/Delta(t) rise (rfu/s), and DeltaCa2+/Delta(t) fall (rfu/s). Contractile parameters are as follows: maximum cell length (microm), minimum cell length (microm), absolute cell shortening (microm), peak DeltaL/Delta(t) shortening (microm/s), and peak DeltaL/Delta(t) relaxation (microm/s). In summary, we succeeded in demonstrating that this system is a unique and valuable tool that allows simultaneous and accurate assessment of contractile parameters and of calcium movements of isolated adult cardiac myocytes.


Assuntos
Sinalização do Cálcio/fisiologia , Processamento de Imagem Assistida por Computador , Miocárdio/citologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Cardiotônicos/farmacologia , Tamanho Celular/efeitos dos fármacos , Tamanho Celular/fisiologia , Proteínas Contráteis/fisiologia , Isoproterenol/farmacologia , Microscopia de Fluorescência , Microscopia de Vídeo , Nitrendipino/farmacologia , Ratos
17.
FASEB J ; 15(12): 2187-95, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11641245

RESUMO

Human congestive heart failure is characterized by complex neurohumoral activation associated with the up-regulation of vasoconstricting and salt-retaining mediators and the compensatory rise of counter-regulatory hormones. In the present study, we provide the first evidence that relaxin (RLX), known as a pregnancy hormone, represents a potential compensatory mediator in human heart failure: plasma concentrations of RLX and myocardial expression of the two RLX genes (H1 and H2) correlate with the severity of disease and RLX responds to therapy. The failing human heart is a relevant source of circulating RLX peptides, and myocytes as well as interstitial cells produce RLX. Elevation of ventricular filling pressure up-regulates RLX expression and the hormone acts as a potent inhibitor of endothelin 1, the most powerful vasoconstrictor in heart failure. Furthermore, RLX modulates effects of angiotensin II, another crucial mediator. Our data identify RLX as a new player in human heart failure with potential diagnostic and therapeutic relevance.


Assuntos
Insuficiência Cardíaca/etiologia , Relaxina/fisiologia , Animais , Ácido Aspártico Endopeptidases/biossíntese , Ácido Aspártico Endopeptidases/genética , Bovinos , Células Cultivadas , Endotelina-1/biossíntese , Feminino , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Técnicas de Cultura de Órgãos , Pró-Proteína Convertases , Precursores de Proteínas/metabolismo , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Relaxina/genética , Relaxina/farmacologia , Regulação para Cima , Pressão Ventricular
18.
J Cardiovasc Pharmacol ; 38(5): 666-71, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11602813

RESUMO

The present study was designed to investigate, in patients with severe heart failure, the dose-dependent acute hemodynamic effects of celiprolol versus those of esmolol. Celiprolol is a beta 1 -receptor blocker with vasodilating properties, whereas esmolol is an ultra-short-acting beta 1 -blocker. Included were 14 patients with decompensated chronic heart failure (NYHA class IV) due to coronary heart disease (n = 8) or to dilated cardiomyopathy (n = 6). Each patient received both celiprolol and esmolol in random fashion. The beta-blockers were administered in four dose tiers, with an increase in dosage every 15 min. Hemodynamic measurements were obtained with a Swan-Ganz thermodilution catheter. Administration of celiprolol (5, 10, 20, and 50 microg/kg) took place intravenously. After intravenous administration of a loading dose of 500 microg/kg, we continuously infused esmolol at increasing doses, which were individually titrated for each patient. Mean infusion rates of esmolol were as follows: 40, 75, 140, and 230 micromol/kg per minute. Celiprolol and esmolol induced a comparable dose-dependent decrease in heart rate to a minimum of -10% below baseline. Esmolol caused a significant dose-dependent decrease (-25% below baseline at the highest dose level) in cardiac index (CI). After administration of celiprolol, CI decreased only transiently (-10% below baseline at the second and third dose level) and did not differ from the baseline at the highest dose level. For treatment of severe heart failure, initiation of intravenous beta-blocker therapy with low doses of a beta 1 -blocker with vasodilating effects may have hemodynamic advantages over conventional beta-blockade.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Celiprolol/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Propanolaminas/uso terapêutico , Adulto , Idoso , Relação Dose-Resposta a Droga , Meia-Vida , Hemodinâmica/efeitos dos fármacos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Propanolaminas/farmacocinética
19.
J Am Coll Cardiol ; 38(4): 1023-7, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11583876

RESUMO

OBJECTIVES: We sought to determine the role of the -5T/C polymorphism of the platelet glycoprotein (GP) Ibalpha as a potential risk factor for coronary artery disease (CAD) and adverse events complicating a coronary catheter intervention. BACKGROUND: The platelet GP Ib-IX-V receptor complex plays a crucial role in arterial thrombus formation. The -5T/C polymorphism of GP Ibalpha is associated with increased receptor density. METHODS: We genotyped 1,000 patients with angiographically confirmed CAD, as well as 1,000 age- and gender-matched control subjects, for this polymorphism by polymerase chain reaction/restriction fragment length polymorphism. Among the patients with CAD, 269 underwent percutaneous transluminal coronary angioplasty (PTCA), 103 underwent directional coronary atherectomy and 278 underwent stenting. This intervention group was followed for a 30-day composite end point of target vessel revascularization, myocardial infarction or death. RESULTS: Carriers of the -5C allele were significantly over-represented in the group of patients developing acute coronary syndromes (relative risk [RR] 1.43, 95% confidence interval [CI] 1.05 to 1.95, p = 0.02). The -5C allele furthermore predicted an increased risk for developing complications after PTCA (RR 3.75, 95% CI 1.15 to 12.27, p = 0.029). CONCLUSIONS: The -5C allele of the GP Ibalpha Kozak polymorphism may represent a risk factor in clinical conditions in which thrombosis plays an important role, such as in acute coronary syndromes and in complications after PTCA.


Assuntos
Trombose Coronária/genética , Trombose Coronária/terapia , Revascularização Miocárdica , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Polimorfismo Genético , Idoso , Alelos , Angioplastia Coronária com Balão , Aterectomia Coronária , Angiografia Coronária , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Stents
20.
Eur J Pharmacol ; 423(2-3): 115-9, 2001 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-11448474

RESUMO

beta(1)-Adrenoceptor autoantibodies are present in approximately 30% of patients suffering from dilated cardiomyopathy. The inotropic effects mediated by these antibodies remain to be studied. Monoclonal antibodies were raised against a peptide corresponding to the second extracellular loop of the human beta(1)-adrenoceptor in balb/C mouse (n=6), and were characterized by enzyme immunoassay after purification by protein A. Purified immunoglobulin G from non-immunized animals (controls) did not influence Ca(2+) transient and cell shortening of rat cardiomyocytes measured by confocal-laser-scanning-microscopy. beta(1)-adrenoceptor antibodies caused a dose-related increase in Ca(2+) transient (dilution 1:2: +35.3+/-5.1%), and in cell shortening (dilution 1:2: +40.5+/-6.3%) (P<0.01 vs. controls). The effect of the beta(1)-adrenoceptor antibodies was blocked by the antigenic peptide and by the antagonist metoprolol. In addition, beta(1)-adrenoceptor antibodies induced a dose-dependent increase of the cyclic adenosine monophosphate. The inotropic response induced by isoproterenol was attenuated by the beta(1)-adrenoceptor antibody. beta(1)-adrenoceptor antibodies as partial agonists induce a specific positive inotropic effect via the protein-kinase-A-cascade.


Assuntos
Anticorpos Monoclonais/farmacologia , Coração/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Miocárdio/citologia , Receptores Adrenérgicos beta 1/imunologia , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Anticorpos Monoclonais/imunologia , Tamanho Celular/efeitos dos fármacos , Células Cultivadas , AMP Cíclico/análogos & derivados , AMP Cíclico/farmacologia , Relação Dose-Resposta a Droga , Coração/fisiologia , Humanos , Isoproterenol/farmacologia , Metoprolol/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Miocárdio/metabolismo , Propanolaminas/farmacologia , Ratos , Receptores Adrenérgicos beta 1/química , Tionucleotídeos/farmacologia
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