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1.
N Engl J Med ; 343(4): 246-53, 2000 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-10911006

RESUMO

BACKGROUND: Intravenous infusion of nesiritide, a brain (B-type) natriuretic peptide, has beneficial hemodynamic effects in patients with decompensated congestive heart failure. We investigated the clinical use of nesiritide in such patients. METHODS: Patients hospitalized because of symptomatic congestive heart failure were enrolled in either an efficacy trial or a comparative trial. In the efficacy trial, which required the placement of a Swan-Ganz catheter, 127 patients with a pulmonary-capillary wedge pressure of 18 mm Hg or higher and a cardiac index of 2.7 liters per minute per square meter of body-surface area or less were randomly assigned to double-blind treatment with placebo or nesiritide (infused at a rate of 0.015 or 0.030 microg per kilogram of body weight per minute) for six hours. In the comparative trial, which did not require hemodynamic monitoring, 305 patients were randomly assigned to open-label therapy with standard agents or nesiritide for up to seven days. RESULTS: In the efficacy trial, at six hours, nesiritide infusion at rates of 0.015 and 0.030 microg per kilogram per minute decreased pulmonary-capillary wedge pressure by 6.0 and 9.6 mm Hg, respectively (as compared with an increase of 2.0 mm Hg with placebo, P<0.001), resulted in improvements in global clinical status in 60 percent and 67 percent of the patients (as compared with 14 percent of those receiving placebo, P<0.001), reduced dyspnea in 57 percent and 53 percent of the patients (as compared with 12 percent of those receiving placebo, P<0.001), and reduced fatigue in 32 percent and 38 percent of the patients (as compared with 5 percent of those receiving placebo, P<0.001). In the comparative trial, the improvements in global clinical status, dyspnea, and fatigue were sustained with nesiritide therapy for up to seven days and were similar to those observed with standard intravenous therapy for heart failure. The most common side effect was dose-related hypotension, which was usually asymptomatic. CONCLUSIONS: In patients hospitalized with decompensated congestive heart failure, nesiritide improves hemodynamic function and clinical status. Nesiritide is useful for the treatment of decompensated congestive heart failure.


Assuntos
Fator Natriurético Atrial/uso terapêutico , Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Fator Natriurético Atrial/efeitos adversos , Fator Natriurético Atrial/farmacologia , Cardiotônicos/efeitos adversos , Cardiotônicos/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Dispneia/tratamento farmacológico , Fadiga/tratamento farmacológico , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico , Pressão Propulsora Pulmonar/efeitos dos fármacos , Vasodilatadores/uso terapêutico
2.
J Am Coll Cardiol ; 30(2): 569-75, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9247534

RESUMO

OBJECTIVES: We sought to document the common mechanisms of the antiatherogenic effects of the cholesterol-lowering hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin, the dihydropyridine Ca2+ blocker amlodipine and the antioxidant vitamin E. BACKGROUND: Vitamin E, HMG-CoA reductase inhibitors and Ca2+ blockers each inhibit atherosclerosis in hypercholesterolemic animals. METHODS: New Zealand White rabbits were fed regular chow (Group A), chow with 1% cholesterol (Group B), 1% cholesterol diet plus lovastatin (Group C), 1% cholesterol diet plus vitamin E (Group D) or 1% cholesterol diet plus amlodipine (Group E) for 12 weeks. The extent of aortic atherosclerosis was measured by planimetry of the sudanophilic area. Malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured as indexes of lipid peroxidation and antioxidant activity, respectively. RESULTS: Group A rabbits showed no atherosclerosis, whereas Group B rabbits had 17.4 +/- 9.3% (mean +/- SD) of the aorta covered with atherosclerosis, and Groups C, D and E rabbits had significantly less atherosclerosis. Plasma SOD activity was lower in Group B than in Group A (6.9 +/- 1.1 vs. 12.8 +/- 1.5 U/ml, p < 0.01) and was preserved in the groups given lovastatin, vitamin E or amlodipine with a high cholesterol diet. The serum MDA level was higher in Group B rabbits than Group A rabbits (12.1 +/- 2.6 vs. 1.2 +/- 0.1 nmol/ml, p < 0.01) and increased minimally in rabbits given lovastatin, vitamin E or amlodipine with a high cholesterol diet. In in vitro experiments, both lovastatin and amlodipine preserved SOD activity and reduced the oxidizability of low density lipoproteins by rabbit leukocytes. CONCLUSIONS: This study suggests that a reduction in lipid peroxidation and preservation of SOD may be common mechanisms of antiatherosclerotic effects of lovastatin, vitamin E and amlodipine.


Assuntos
Anlodipino/farmacologia , Anticolesterolemiantes/farmacologia , Antioxidantes/farmacologia , Arteriosclerose/prevenção & controle , Bloqueadores dos Canais de Cálcio/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases , Peroxidação de Lipídeos/efeitos dos fármacos , Lovastatina/farmacologia , Vitamina E/farmacologia , Animais , Dieta Aterogênica , Coelhos , Superóxido Dismutase/metabolismo
3.
J Cardiovasc Pharmacol ; 28(3): 418-24, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8877589

RESUMO

Development of vascular tolerance to nitroglycerin (NTG) has been attributed to sulfhydryl (SH) depletion, guanylate cyclase desensitization, or both. Controversy regarding the precise contribution of these mechanisms may be due to variations in experimental design. To examine further the biochemical basis of NTG tolerance, norepinephrine (NE)-precontracted rat aortic rings were exposed to NTG (10(-5)M), which resulted in 84 +/- 6% relaxation. Other rings were first superfused with NTG (10(-6)M) and then contracted with NE. These rings showed a marked tolerance to the vasorelaxant effects of NTG (maximal relaxation 20 +/- 5%, n = 15, p < 0.001 vs. control rings). Similar tolerance to NTG was observed when the vascular rings were first superfused with acetylcholine (ACh 10(-6)M), indicating cross-tolerance between ACh and NTG. Treatment of NTG-tolerant rings with N-acetylcysteine (NAC) (10(-5)M) did not restore vascular smooth muscle (VSM) relaxation in response to NTG (maximal relaxation 23 +/- 5%, n = 8), suggesting that SH depletion may not be the basis of NTG tolerance in these experiments. Parallel sets of NTG-tolerant aortic rings were contracted with endothelin-1 (ET-1, n = 5) or the endothelium-derived relaxing factor (EDRF) synthase inhibitor NG-monomethyl L-arginine (L-NMMA, 10(-4)M, n = 8). In both ET-1- and L-NMMA-contracted rings, vascular relaxation in response to NTG was preserved (80 +/- 6 and 88 +/- 8% relaxation, respectively). Measurement of cyclic GMP in aortic rings showed marked accumulation on initial exposure of tissues to NTG (310 +/- 10 fmol/mg), whereas the NTG-tolerant rings showed much less cyclic GMP accumulation (48 +/- 29 fmol/mg). Rings contracted with L-NMMA or ET-1, but not NE, accumulated cyclic GMP when exposed to NTG (280 +/- 20 fmol/mg). These data indicate that NTG tolerance develops on exposure of vascular rings superfused with NTG or ACh and is probably not related to tissue SH depletion. Contraction of NTG-tolerant rings with ET-1 or L-NMMA restores NTG-mediated relaxation.


Assuntos
Acetilcisteína/farmacologia , Endotelina-1/farmacologia , Inibidores Enzimáticos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Óxido Nítrico Sintase/antagonistas & inibidores , Nitroglicerina/farmacologia , Vasodilatadores/farmacologia , ômega-N-Metilarginina/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , GMP Cíclico/metabolismo , Tolerância a Medicamentos , Técnicas In Vitro , Relaxamento Muscular/efeitos dos fármacos , Ratos
4.
Am Heart J ; 132(1 Pt 1): 1-8, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8701848

RESUMO

Atherosclerosis is increasingly thought to be a chronic inflammatory disease. Inflammation requires transmigration of leukocytes from the circulation to the tissues. Adhesion of leukocytes to endothelial calls is the initial event in an inflammatory response and is mediated by expression of several adhesion molecules. In this study we characterize the contribution of intercellular adhesion molecules (ICAM-1) and L-selectin in patients with different coronary artery disease syndromes. Serum concentrations of cICAM-1 and sL-selectin were measured by enzyme-linked immunosorbent assay in 31 patients with stable angina, 30 patients with unstable angina, 18 patients with acute myocardial infarction and 20 healthy subjects in a control group. All patients underwent coronary angiography. Mean (+/-SE) cICAM-1 levels were higher (p < 0.05) in patients with stable angina (249 +/- 6 ng/ml), unstable angina (260 +/- 16 ng/ml), or acute myocardial infarction (261 +/- 24 ng/ml) compared with those in subjects in the control group (171 +/- 11 ng/ml). In contrast, levels of sL-selectin were lower (p < 0.01) in patients with stable angina (1.2 +/- 0.1 microg/ml), unstable angina (1.1 +/- 0.6 microg/ml), or acute myocardial infarction (1.1 +/- 0.1 microg/ml) compared with those in subjects in the control group (1.8 +/- 0.1 microg/ml). No difference was found in cICAM-1 or sL-selectin levels among patients with stable angina, unstable angina, or acute myocardial infarction. No correlation was seen between cICAM-1 or sL-selectin levels and extent (or severity) of coronary artery disease or leukocyte count. L-selectin expression was observed to be depressed in patients with severe angina compared with that in members of the control group. To examine the mechanism of reduction in sL-selectin levels and L-selectin expression on leukocytes, leukocytes from the control group were stimulated in vitro. Stimulation of leukocytes resulted in a rapid downregulation of surface L-selectin expression, measured by flowcytometry, similar to the suppressed expression of L-selectin found on leukocytes from patients with coronary artery disease. In conclusion, altered cICAM-1 and sL-selectin levels in patients with coronary artery disease reflect the presence of a chronic inflammatory process. This inflammatory process results in downregulation of leukocyte expression of L-selectin and thus lower circulating sL-selectin levels.


Assuntos
Molécula 1 de Adesão Intercelular/sangue , Selectina L/sangue , Isquemia Miocárdica/sangue , Angina Pectoris/sangue , Angina Instável/sangue , Adesão Celular , Movimento Celular , Doença Crônica , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença das Coronárias/sangue , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Regulação da Expressão Gênica , Humanos , Inflamação , Selectina L/genética , Contagem de Leucócitos , Leucócitos/metabolismo , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue
5.
Clin Cardiol ; 19(6): 455-60, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8790948

RESUMO

Measures of disease severity used in the evaluation of patients with heart failure include survival data, the New York Heart Association classification, ejection fraction, functional assessments, exercise protocols, rest and exercise hemodynamic data, and biochemical parameters including catecholamine levels and serum sodium. Clinicians must integrate these multiple variables into an overall assessment. An overview of the clinical application of these techniques in the evaluation and treatment of patients with heart failure is presented.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Coração/fisiologia , Débito Cardíaco/fisiologia , Catecolaminas/sangue , Teste de Esforço , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/terapia , Transplante de Coração , Hemodinâmica , Humanos , Consumo de Oxigênio/fisiologia , Respiração/fisiologia , Sódio/sangue , Vasodilatadores/uso terapêutico
6.
Am J Cardiol ; 76(4): 314-5, 1995 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-7542431

RESUMO

In summary, dextran 40, when given after coronary stent placement, results in a marked decrease in hematocrit within 24 hours. Hematocrit often returns to near baseline levels within 48 hours of stopping dextran. This phenomenon most likely reflects dextran-related hemodilution. This hemodilutional decrease in hematocrit is often misinterpreted as acute blood loss and may result in blood transfusion in patients with low baseline hematocrit. However, far less aggressive anticoagulation regimens, which do not include dextran, are under investigation in patients undergoing coronary stent placement.


Assuntos
Doença das Coronárias/sangue , Dextranos/uso terapêutico , Hematócrito , Stents , Angioplastia Coronária com Balão , Doença das Coronárias/terapia , Dextranos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Clin Cardiol ; 18(2): 109-11, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7720285

RESUMO

Hemodynamically unstable ventricular arrhythmias induced during electrophysiologic testing almost always respond to prompt application of direct current transthoracic shocks. In rare cases, however, ventricular fibrillation may be refractory to conventional treatment. Recently, a technique of intracardiac defibrillation has been successfully used to resuscitate patients with ventricular fibrillation refractory to transthoracic defibrillation. We describe two patients with a history of myocardial infarction and left ventricular dysfunction who were admitted with symptomatic episodes of ventricular tachycardia. Both had inducible sustained monomorphic ventricular tachycardia. During a repeat electrophysiologic study in Patient No. 1 on procainamide and at the initial study in Patient No. 2, right ventricular burst pacing to terminate ventricular tachycardia resulted in ventricular fibrillation refractory to resuscitation efforts, including transthoracic defibrillation with 360 J. Emergency intracardiac defibrillation with 200 and 360 J, respectively, successfully converted both patients to sinus rhythm. Both patients were subsequently discharged from the hospital on amiodarone. These cases illustrate the life-saving capabilities of intracardiac defibrillation.


Assuntos
Cardioversão Elétrica , Fibrilação Ventricular/terapia , Idoso , Cardioversão Elétrica/métodos , Eletrocardiografia , Emergências , Humanos , Masculino , Pessoa de Meia-Idade , Fibrilação Ventricular/diagnóstico
9.
Am J Med Sci ; 306(4): 236-40, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8213892

RESUMO

Bacillary angiomatosis is a newly characterized infectious disease occurring mainly in patients with AIDS. Most patients have cutaneous angiomatosis lesions resembling Kaposi's sarcoma or pyogenic granuloma. Although the disease may be life-threatening if not treated, it is curable with appropriate antibiotic therapy. A patient had a fever, nightsweats, abdominal pain, pleural effusions, and asymmetric peripheral lymphadenopathy. Computed tomography of the chest and abdomen revealed a unique pattern of enhancement of lymph nodes that, to this research team's knowledge, has not been reported previously with this condition. Appropriate antibiotic therapy resulted in a complete resolution of the disease. Included is a discussion of the clinical presentation, etiology, histology, and treatment of bacillary angiomatosis.


Assuntos
Angiomatose Bacilar/complicações , Doenças Linfáticas/complicações , Adulto , Angiomatose Bacilar/diagnóstico por imagem , Humanos , Doenças Linfáticas/diagnóstico por imagem , Masculino , Radiografia Abdominal , Radiografia Torácica , Tomografia Computadorizada por Raios X
10.
J Cardiovasc Pharmacol ; 19(5): 701-8, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1381767

RESUMO

Anoxia and reoxygenation modulate vasomotor tone. To determine the effect of the slow channel calcium blockers verapamil and diltiazem in vascular smooth muscle contraction during states of altered oxygenation, rat aortic rings with intact endothelium were contracted with norepinephrine (NE) or the thromboxane A2 mimic U46,619 and then exposed abruptly to anoxia (switch from 95% O2 to 95% N2) for 30 min and then reoxygenated (switch from 95% N2 to 95% O2). Anoxia caused a transient 40 +/- 9% (mean +/- SE, n = 15) increase in contraction, whereas reoxygenation resulted in an initial decrease followed by a large (83 +/- 21%) increase in contraction. Treatment of vascular rings with verapamil or diltiazem (1 microgram/ml or 2 microM) decreased contractile response to the agonists (p less than 0.01). Both these agents consistently augmented the magnitude and duration of anoxia-induced contraction (p less than 0.01). In other experiments, pretreatment of vascular rings with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endothelium-derived relaxing factor (EDRF) synthesis, or with oxyhemoglobin, an inhibitor of EDRF activity, or de-endothelialization resulted in marked (p less than 0.01) decrease in anoxic contraction, indicating that anoxia-induced contraction is caused by modulation of EDRF. Treatment of aortic rings with verapamil also reduced acetylcholine-mediated relaxation (from 86 +/- 6% to 45 +/- 5%, p less than 0.02) and cyclic GMP accumulation (from 192 +/- 53 to 111 +/- 35 fmol/mg, p less than 0.02), indicating reduction in EDRF synthesis or activity by verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Diltiazem/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Oxigênio/farmacologia , Vasoconstrição/efeitos dos fármacos , Verapamil/farmacologia , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico , Acetilcolina/farmacologia , Animais , Aorta , Técnicas In Vitro , Indometacina/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Norepinefrina/farmacologia , Oxiemoglobinas/farmacologia , Endoperóxidos Sintéticos de Prostaglandinas/farmacologia , Ratos , Ratos Endogâmicos , Tromboxano A2/farmacologia
11.
Clin Cardiol ; 14(8): 692-5, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1914275

RESUMO

A 34-year-old woman presented with her fourth occurrence of an atrial myxoma and a right lower lung field mass. Her surgical history was extensive. In addition to resection of three previous atrial myxomas, she had undergone resection of her adrenal glands as a teenager because of Cushing's syndrome, and a hysterectomy at age 26 revealed a myxoid leiomyoma. Family history was remarkable as a maternal uncle and daughter died from embolic complications of left atrial myxomas and her sister previously had a left atrial myxoma resected. The patient underwent uncomplicated removal of the myxoma, and resection of the lung mass revealed a granuloma. A review of typical and atypical aspects of cardiac myxomas is provided including a rare and recently described syndrome of familial cardiac myxoma associated with Cushing's syndrome, spotty skin pigmentation and other myxoid tumors.


Assuntos
Síndrome de Cushing/complicações , Doenças Genéticas Inatas/genética , Neoplasias Cardíacas/complicações , Mixoma/complicações , Adulto , Biópsia , Ecocardiografia , Esôfago/diagnóstico por imagem , Feminino , Genes Dominantes , Átrios do Coração , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/genética , Humanos , Mixoma/diagnóstico , Mixoma/genética , Linhagem , Fotomicrografia , Recidiva
12.
Life Sci ; 49(23): 1739-46, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1658520

RESUMO

To determine the mechanism of anoxic vasoconstriction, precontracted rat aortic rings were exposed to 95% N2, which caused additional contraction. Reoxygenation (95% O2) resulted in initial relaxation followed by contraction. Indomethacin did not affect anoxic contraction or reoxygenation-mediated events, but NG-monomethyl-1-arginine, which inhibits EDRF synthesis, and oxyhemoglobin, which reduces EDRF activity, markedly decreased anoxic contraction and reoxygenation relaxation, and potentiated subsequent contraction. Superoxide dismutase did not affect anoxic contraction, but potentiated reoxygenation relaxation and attenuated subsequent contraction. Endothelin concentrations remained unchanged throughout anoxia and reoxygenation. Thus, anoxic contraction and reoxygenation-mediated early relaxation appear to be due to changes in EDRF. On the other hand, reoxygenation-induced contraction appears related to release of superoxide radicals.


Assuntos
Oxigênio/metabolismo , Superóxidos/metabolismo , Vasoconstrição , Animais , Aorta Torácica , Arginina/análogos & derivados , Arginina/farmacologia , Endotelinas/metabolismo , Endotélio Vascular/fisiologia , Hipóxia , Indometacina/farmacologia , Oxiemoglobinas/farmacologia , Ratos , Ratos Endogâmicos , Superóxido Dismutase/metabolismo , Vasoconstrição/efeitos dos fármacos , ômega-N-Metilarginina
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