RESUMO
BACKGROUND: Nitric oxide (NO) is a modulator of left ventricular hypertrophy (LVH) and myocardial relaxation. The impact of NO availability on development of LVH has never been demonstrated in humans. We tested the hypotheses that elevation of asymmetric dimethylarginine (ADMA) concentrations (biochemical marker of decreased NO generation), and impairment of vascular responsiveness to NO donor GTN, would each predict the presence of LVH and associated LV diastolic dysfunction in a normal aging population. METHODS AND RESULTS: In 74 subjects aged 68±6 years, LV volumes and mass indexed to height(2.7) (LVMI) were calculated from cardiac MRI. Despite the absence of clinically-defined LVH, there was a relationship (r=0.29; p=0.01) between systolic BP and LVMI. Both elevation of ADMA levels to the highest quartile or impairment of GTN responsiveness (determined by applanation tonometry) to the lowest quartile were determinants of LVMI independent of systolic BP (p=0.01 and p=0.03, respectively). Filling pressure (E/E' ratio from echocardiography) was increased in patients with impaired vascular NO responsiveness (p<0.05) irrespective of LVMI. ADMA remained a significant determinant of LVMI on multivariate analysis. CONCLUSIONS: These data imply that NO bioavailability within the myocardium modulates earliest stages of LVH development and facilitates development of diastolic dysfunction at a given LV mass.
Assuntos
Arginina/análogos & derivados , Hipertrofia Ventricular Esquerda/sangue , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico/metabolismo , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Arginina/metabolismo , Pressão Sanguínea , Ecocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Miocárdio/metabolismo , Óxido Nítrico/análise , Óxido Nítrico Sintase/sangue , Valor Preditivo dos Testes , SoftwareRESUMO
Hypertrophic cardiomyopathy (HCM) is diagnosed on the basis of left ventricular (LV) hypertrophy for which there is insufficient explanation (e.g. mild hypertension or mild aortic stenosis with marked hypertrophy). Echocardiography is an invaluable tool in the diagnosis and follow-up of patients with HCM. Echocardiographic assessment requires a comprehensive assessment in several imaging planes with careful attention to correct beam alignment in order to minimize errors in the measurement of LV wall thickness and appropriate identification of hypertrophy with an unusual distribution.
Assuntos
Cardiomiopatia Hipertrófica/diagnóstico por imagem , Ecocardiografia/métodos , Cardiomiopatia Hipertrófica/fisiopatologia , Cardiomiopatia Hipertrófica/terapia , Diagnóstico Diferencial , Diástole/fisiologia , Humanos , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/terapia , Prognóstico , Sístole/fisiologia , Ultrassonografia de Intervenção , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagem , Obstrução do Fluxo Ventricular Externo/fisiopatologia , Obstrução do Fluxo Ventricular Externo/cirurgiaRESUMO
Heart failure (HF) is a syndrome and not a diagnosis. Aetiology and precipitants for decompensation are often not sought. Care is also often based upon protocols, with widespread prescription of drugs validated in systolic HF, for patients with other forms of HF for example HF with preserved ejection fraction which can account for almost half of patients with HF in the UK. Therefore, service design and configuration by healthcare providers should based upon quality and not only feasibility, as protocol-based treatment will inevitably diminish the quality of care for patients with HF and result in both inappropriate care in many cases as well as reduced access to advanced evidence based and NICE approved therapies. Expertise is therefore of paramount importance in managing patients with HF.
Assuntos
Insuficiência Cardíaca/diagnóstico , Ecocardiografia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , HumanosRESUMO
Several diseases are associated with perturbations in redox signaling and aberrant hydrogen sulfide metabolism, and numerous analytical methods exist for the measurement of the sulfur-containing species affected. However, uncertainty remains about their concentrations and speciation in cells/biofluids, perhaps in part due to differences in sample processing and detection principles. Using ultrahigh-performance liquid chromatography in combination with electrospray-ionization tandem mass spectrometry we here outline a specific and sensitive platform for the simultaneous measurement of 12 analytes, including total and free thiols, their disulfides and sulfide in complex biological matrices such as blood, saliva and urine. Total assay run time is <â¯10â¯min, enabling high-throughput analysis. Enhanced sensitivity and avoidance of artifactual thiol oxidation is achieved by taking advantage of the rapid reaction of sulfhydryl groups with N-ethylmaleimide. We optimized the analytical procedure for detection and separation conditions, linearity and precision including three stable isotope labelled standards. Its versatility for future more comprehensive coverage of the thiol redox metabolome was demonstrated by implementing additional analytes such as methanethiol, N-acetylcysteine, and coenzyme A. Apparent plasma sulfide concentrations were found to vary substantially with sample pretreatment and nature of the alkylating agent. In addition to protein binding in the form of mixed disulfides (S-thiolation) a significant fraction of aminothiols and sulfide appears to be also non-covalently associated with proteins. Methodological accuracy was tested by comparing the plasma redox status of 10 healthy human volunteers to a well-established protocol optimized for reduced/oxidized glutathione. In a proof-of-principle study a deeper analysis of the thiol redox metabolome including free reduced/oxidized as well as bound thiols and sulfide was performed. Additional determination of acid-labile sulfide/thiols was demonstrated in human blood cells, urine and saliva. Using this simplified mass spectrometry-based workflow the thiol redox metabolome can be determined in samples from clinical and translational studies, providing a novel prognostic/diagnostic platform for patient stratification, drug monitoring, and identification of new therapeutic approaches in redox diseases.
Assuntos
Dissulfetos/isolamento & purificação , Metaboloma , Estresse Oxidativo , Compostos de Sulfidrila/isolamento & purificação , Cromatografia Líquida , Dissulfetos/sangue , Dissulfetos/urina , Glutationa/sangue , Glutationa/isolamento & purificação , Glutationa/urina , Humanos , Espectrometria de Massas , Oxirredução , Compostos de Sulfidrila/sangue , Compostos de Sulfidrila/urinaRESUMO
OBJECTIVE: Eisenmenger syndrome is characterized by severe and lifelong hypoxemia and pulmonary hypertension. Despite this, patients do surprisingly well and report a reasonable quality of life. The aim of this study was to investigate whether these patients undergo adaptation of their skeletal and cardiac muscle energy metabolism which would help explain this paradox. DESIGN AND SETTING: Ten patients with Eisenmenger syndrome and eight age- and sex-matched healthy volunteers underwent symptom-limited treadmill cardiopulmonary exercise testing, transthoracic echocardiography and (31) P magnetic resonance spectroscopy of cardiac and skeletal muscle. Five subjects from each group also underwent near infrared spectroscopy to assess muscle oxygenation. RESULTS: Despite having a significantly lower peak VO2 , patients with Eisenmenger syndrome have a similar skeletal muscle phosphocreatine (PCr) recovery, a measure of oxidative capacity, when compared to healthy controls (34.9 s ± 2.9 s vs. 35.2 s ± 1.7 s, P = .9). Furthermore their intracellular pH falls to similar levels during exercise suggesting they are not reliant on early anaerobic metabolism (0.3 ± 0.06 vs. 0.28 ± 0.04, P = .7). While their right ventricular systolic function remained good, the Eisenmenger group had a lower cardiac PCr/ATP ratio compared to the control group (1.55 ± 0.10 vs. 2.17 ± 0.15, P < .05). CONCLUSIONS: These results show that adult patients with Eisenmenger syndrome have undergone beneficial physiological adaptations of both skeletal and cardiac muscle. This may, in part, explain their surprisingly good survival despite a lifetime of severe hypoxemia and adverse cardiopulmonary hemodynamics.
Assuntos
Complexo de Eisenmenger/complicações , Metabolismo Energético , Hipóxia/etiologia , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Adaptação Fisiológica , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Ecocardiografia , Complexo de Eisenmenger/diagnóstico , Complexo de Eisenmenger/metabolismo , Complexo de Eisenmenger/fisiopatologia , Teste de Esforço , Tolerância ao Exercício , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hipóxia/diagnóstico , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Espectroscopia de Ressonância Magnética/métodos , Masculino , Músculo Esquelético/fisiopatologia , Consumo de Oxigênio , Fosfocreatina/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho , Função Ventricular DireitaRESUMO
BACKGROUND: Although nitric oxide (NO) is known to play an important part in the regulation of arterial tone, little is known about its role in veins. The aim of this study was to investigate the role of basal and stimulated NO activity in the regulation of tone of the human venous capacitance bed. METHODS AND RESULTS: We measured venous tone using radionuclide forearm venous plethysmography in 24 healthy subjects with no cardiovascular risk factors. In 13 subjects, basal NO activity was assessed by measuring the effects on venous tone of an intra-arterial infusion of the NO synthase inhibitor N-monomethyl-L-arginine (L-NMMA). In the remaining 11 subjects, stimulated NO activity was evaluated by measuring the effects of an intra-arterial infusion of incremental doses of carbachol, followed in a subgroup by coinfusion with L-NMMA. Infusion of carbachol caused dose-dependent venodilation, with a maximal reduction in forearm venous tone of 40.1+/-12.5% (P<0.0001). Carbachol-induced venodilation was inhibited by L-NMMA (48.9+/-6.2% reversal of maximal venodilation, P<0.01). Infusion of L-NMMA alone caused venoconstriction (9.1+/-6.4% increase in venous tone, P=0.002). CONCLUSIONS: Human forearm capacitance veins exhibit both stimulated and basal NO activity, which indicates that NO contributes not only to the regulation of venous tone but also to resting venous tone in healthy human subjects.
Assuntos
Endotélio Vascular/metabolismo , Óxido Nítrico/fisiologia , Sistema Vasomotor/fisiologia , Veias/fisiologia , Adulto , Carbacol/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Antebraço/irrigação sanguínea , Humanos , Hidralazina/farmacologia , Injeções Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Resistência Vascular , Vasodilatadores/farmacologia , Veias/efeitos dos fármacos , ômega-N-Metilarginina/farmacologiaRESUMO
BACKGROUND: Exaggerated postprandial lipemia (PPL) is a factor in atherogenesis, involving endothelial dysfunction and enhanced oxidative stress. We examined the effect of ciprofibrate therapy on these parameters in type 2 diabetes mellitus. METHODS AND RESULTS: Twenty patients entered a 3-month, double-blind, placebo-controlled study. Each subject was studied fasting and after a fatty meal, at baseline, and after 3 months of treatment. Glucose and lipid profiles were measured over an 8-hour postprandial period. Endothelial function (flow-mediated endothelium-dependent vasodilatation [FMD]) and oxidative stress (electron paramagnetic resonance spectroscopy) were measured after fasting and 4 hours postprandially. At baseline, both groups exhibited similar PPL and deterioration in endothelial function. After ciprofibrate, fasting and postprandial FMD values were significantly higher (from 3.8+/-1. 8% and 1.8+/-1.3% to 4.8+/-1.1% and 3.4+/-1.1%; P<0.05). This was mirrored by a fall in fasting and postprandial triglycerides (3. 1+/-2.1 and 6.6+/-4.1 mmol/L to 1.5+/-0.8 and 2.8+/-1.3 mmol/L, P<0. 05). Fasting and postprandial HDL cholesterol was also elevated (0. 9+/-0.1 and 0.8+/-0.1 mmol/L and 1.2+/-0.2 and 1.2+/-0.1 mmol/L, P<0. 05). There were no changes in total or LDL cholesterol. Fasting and postprandial triglyceride enrichment of all lipoproteins was attenuated, with cholesterol depletion of VLDL and enrichment of HDL. There were similar postprandial increases in oxidative stress in both groups at baseline, which was significantly attenuated by ciprofibrate (0.3+/-0.6 versus 1.5+/-1.1 U, P<0.05). CONCLUSIONS: This study demonstrates that fibrate therapy improves fasting and postprandial endothelial function in type 2 diabetes. Attenuation of PPL and the associated oxidative stress, with increased HDL cholesterol levels, may be important.
Assuntos
Ácido Clofíbrico/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Adulto , Análise de Variância , Área Sob a Curva , HDL-Colesterol/sangue , Ácido Clofíbrico/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Endotélio Vascular/fisiopatologia , Feminino , Ácidos Fíbricos , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Período Pós-Prandial , Triglicerídeos/sangueRESUMO
BACKGROUND: Left ventricular (LV) pacing improves hemodynamics in patients with heart failure. We hypothesized that at least part of this benefit occurs by minimization of external constraint to LV filling from ventricular interaction. METHODS AND RESULTS: We present median values (interquartile ranges) for 13 heart failure patients with LV pacing systems implanted for New York Heart Association class III/IV limitation. We used the conductance catheter method to measure LV pressure and volume simultaneously. External constraint was measured from the end-diastolic pressure-volume relation recorded during inferior vena caval occlusion, during LV pacing, and while pacing was suspended. External constraint to LV filling was reduced by 3.0 (4.6 to 0.6) mm Hg from 4.8 (0.6 to 7.5) mm Hg (P<0.01) in response to LV pacing; effective filling pressure (LV end-diastolic pressure minus external constraint) increased by 4.0 (2.2 to 5.8) mm Hg from 17.7 (13.3 to 22.6; P<0.01). LV end-diastolic volume increased by 10 (3 to 11) mL from 238 (169 to 295) mL (P=0.01), whereas LV end-systolic volume did not change significantly (-1 [-2 to 3] mL from 180 [124 to 236] mL, P=0.97), which resulted in an increase in stroke volume of 11 (5 to 13) mL from 49 (38 to 59) mL (P<0.01). LV stroke work increased by 720 (550 to 1180) mL . mm Hg from 3400 (2110 to 4480) mL . mm Hg (P=0.01), and maximum dP/dt increased by 120 (2 to 161) mm Hg/s from 635 (521 to 767) mm Hg/s (P=0.03). CONCLUSIONS: This study suggests a potentially important mechanism by which LV pacing may produce hemodynamic benefit. LV pacing minimizes external constraint to LV filling, resulting in an increase in effective filling pressure; the consequent increase in LV end-diastolic volume increases stroke volume via the Starling mechanism.
Assuntos
Estimulação Cardíaca Artificial , Insuficiência Cardíaca/terapia , Ventrículos do Coração/fisiopatologia , Hemodinâmica , Idoso , Cateterismo Cardíaco , Estudos de Coortes , Diástole , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Pressão , SístoleRESUMO
OBJECTIVES: The purpose of this study was to determine whether restrictive left ventricular (LV) filling patterns are associated with diastolic ventricular interaction in patients with chronic heart failure. BACKGROUND: We recently demonstrated a diastolic ventricular interaction in approximately 50% of a series of patients with chronic heart failure, as evidenced by paradoxic increases in LV end-diastolic volume despite reductions in right ventricular end-diastolic volume during volume unloading achieved by lower body negative pressure (LBNP). We reasoned that such an interaction would impede LV filling in mid and late diastole, but would be minimal in early diastole, resulting in a restrictive LV filling pattern. METHODS: Transmitral flow was assessed using pulsed wave Doppler echocardiography in 30 patients with chronic heart failure and an LV ejection fraction < or = 35%. Peak early (E) and atrial (A) filling velocities and E wave deceleration time were measured. Left ventricular end-diastolic volume was measured using radionuclide ventriculography before and during -30-mm Hg LBNP. RESULTS: Nine of the 11 patients with and 2 of the 16 patients without restrictive LV filling patterns (E/A > 2 or E/A 1 to 2 and E wave deceleration time < or = 140 ms) increased LV end-diastolic volume during LBNP (p = 0.001). The change in LV end-diastolic volume during LBNP was correlated with the baseline A wave velocity (r = -0.52, p = 0.005) and E/A ratio (r = 0.50, p = 0.01). CONCLUSIONS: Restrictive LV filling patterns are associated with diastolic ventricular interaction in patients with chronic heart failure. Volume unloading in the setting of diastolic ventricular interaction allows for increased LV filling. Identifying patients with chronic heart failure and restrictive filling patterns may therefore indicate a group likely to benefit from additional vasodilator therapy.
Assuntos
Débito Cardíaco/fisiologia , Insuficiência Cardíaca/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função do Átrio Esquerdo/fisiologia , Função do Átrio Direito/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Volume Cardíaco/fisiologia , Diástole , Ecocardiografia Doppler de Pulso , Feminino , Previsões , Imagem do Acúmulo Cardíaco de Comporta , Humanos , Pressão Negativa da Região Corporal Inferior , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiopatologia , Compostos Radiofarmacêuticos , Pertecnetato Tc 99m de Sódio , Volume Sistólico/fisiologia , Vasodilatadores/uso terapêutico , Função Ventricular Direita/fisiologia , Pressão Ventricular/fisiologiaRESUMO
Exercise capacity in hypertrophic cardiomyopathy is thought to relate to elevated left atrial pressure as a consequence of impaired diastolic function, but this assumption has not previously been evaluated. Twenty-three patients with hypertrophic cardiomyopathy underwent hemodynamic assessment during symptom-limited maximal exercise with objective measurement of exercise capacity by respiratory gas analysis. Maximal oxygen consumption and anaerobic threshold were 28.1 +/- 7.5 and 21.5 +/- 6.1 ml/kg per min, respectively (the lower limit of reference range in our laboratory is 39 and 27 ml/kg per min, respectively). Maximal oxygen consumption was reduced in 11 of 13 patients who were in New York Heart Association functional class I and who denied limitation of exercise capacity and in all 10 patients who were in functional class II or III. Maximal oxygen consumption and anaerobic threshold were related to peak cardiac index (r = 0.650, p less than 0.001 and r = 0.459, p = 0.03, respectively) and to the increase in cardiac index on exercise (r = 0.677, p less than 0.001 and r = 0.509, p = 0.016, respectively), but not to cardiac index at rest, peak and rest pulmonary capillary wedge pressure, pulmonary capillary wedge pressure at an oxygen consumption of 15 ml/kg per min or the rise in pulmonary capillary wedge pressure on exercise. These findings are not consistent with the hypothesis that elevated left atrial pressure is the major determinant of exercise capacity in patients with hypertrophic cardiomyopathy and they suggest that, as in patients with chronic cardiac failure, other mechanisms should be considered.
Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Exercício Físico , Adulto , Limiar Anaeróbio , Débito Cardíaco , Cardiomiopatia Hipertrófica/fisiopatologia , Teste de Esforço , Feminino , Humanos , Masculino , Consumo de Oxigênio , Pressão Propulsora PulmonarRESUMO
The clinical outcome of 52 consecutive patients with hypertrophic cardiomyopathy who developed paroxysmal (less than 1 week) or established (greater than or equal to 1 week) atrial fibrillation between 1960 and 1985 was examined retrospectively and compared with that of a matched group of patients with hypertrophic cardiomyopathy and sinus rhythm. Follow-up study until death or the present ranged from 6 months to 24 years (median 11 years) from diagnosis and from 6 months to 22 years (median 7 years) from the onset of atrial fibrillation. Atrial fibrillation was present in 6 patients at the time of diagnosis, whereas it developed subsequently in 46. The acute onset of arrhythmia was associated with a change in symptoms in 41 (89%) of the 46. After initial treatment of acute atrial fibrillation, sinus rhythm was restored in 29 (63%) of the 46 patients; 43 (93%) of the 46 returned to their original symptom class. Stepwise logistic regression revealed that shorter duration of arrhythmia and amiodarone therapy were the most powerful predictors of return to sinus rhythm. Sinus rhythm was maintained during a median follow-up period of 5.5 years in 22 of the 29 patients in whom it was restored after initial therapy. During follow-up study, 25 of the 52 patients were treated with conventional therapy alone and 7 with amiodarone alone. Amiodarone therapy was associated with maintenance of sinus rhythm, fewer alterations in drug therapy, fewer embolic episodes and fewer attempted direct current cardioversions (during a shorter follow-up period).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Fibrilação Atrial/etiologia , Cardiomiopatia Hipertrófica/complicações , Adolescente , Adulto , Idoso , Amiodarona/efeitos adversos , Amiodarona/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Criança , Cineangiografia , Quimioterapia Combinada , Ecocardiografia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Angiografia Cintilográfica , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Tecnécio , Tromboembolia/epidemiologiaRESUMO
OBJECTIVES: The goal of this study was to assess whether endothelial dysfunction occurs in the forearm venous capacitance bed of patients with chronic heart failure (CHF) and to determine the role of nitric oxide (NO) in modulating venous tone. BACKGROUND: Control of venous tone is crucially important in CHF. More than 70% of blood volume lies in the venous capacitance beds. Therefore, small changes in venous tone may markedly affect cardiac filling pressures and cardiac output. METHODS: Venous tone was measured using radionuclide forearm venous plethysmography in 24 patients with CHF and 16 age-matched controls. The effect of basal NO activity on venous tone was assessed by infusing N-monomethyl-L-arginine 12 mg/min and stimulated NO using carbachol 15 microg/min. Brachial artery flow-mediated dilation was assessed by ultrasonic wall-tracking. RESULTS: Blockade of basal NO release caused a significant and similar venoconstriction in patients (9.6 +/- 1.8%, p < 0.01) and controls (6.6 +/- 1.7%, p < 0.01). Carbachol-induced venodilation was significant and similar in patients (36.8 +/- 3.9%, p < 0.001) and controls (40.7 +/- 3.9%, p < 0.001). Brachial artery flow-mediated dilation was impaired in patients compared with controls (2.0 +/- 0.6% vs. 7.5 +/- 2.5%, p < 0.01). CONCLUSIONS: Our data indicate that, despite marked impairment of the function of the arterial endothelium, there is preservation of both basal and stimulated NO release in the forearm venous capacitance bed. This may provide important insights into mechanisms of endothelial dysfunction in CHF and the potential for novel therapy.
Assuntos
Endotélio Vascular/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Capacitância Vascular , Veias/fisiopatologia , Idoso , Artérias/fisiopatologia , Carbacol/farmacologia , Doença Crônica , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/farmacologia , Feminino , Antebraço/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Vasodilatação , ômega-N-Metilarginina/farmacologiaRESUMO
A major goal in the management of patients with hypertrophic cardiomyopathy is the prediction of sudden death. To evaluate the high gain signal-averaged electrocardiogram (ECG) in this setting, 64 patients with hypertrophic cardiomyopathy and 50 age- and gender-matched control subjects were studied. An abnormal signal-averaged ECG was more common in patients than in control subjects: 13 (20%) of 64 patients with hypertrophic cardiomyopathy had abnormalities compared with 2 (4%) of the 50 control subjects (p less than 0.001). There was a significant association between the presence of nonsustained ventricular tachycardia on 48 h ECG Holter monitoring and the presence of an abnormal signal-averaged ECG: 8 (47%) of the 17 patients with nonsustained ventricular tachycardia and 6 (86%) of 7 patients with more than three episodes of nonsustained ventricular tachycardia per 24 h had signal-averaged ECG abnormalities. There was no association between an abnormal signal-averaged ECG and a family history of premature sudden cardiac death, a history of syncope, symptomatic status, maximal left ventricular wall thickness, the presence of systolic anterior motion of the mitral valve or maximal rate of oxygen uptake on exercise. However, of four patients with a history of cardiac arrest, three had an abnormal signal-averaged ECG. Sensitivity was 50%; specificity was 93% and positive predictive accuracy was 77% for the signal-averaged ECG in detecting patients with electrical instability (defined as a history of cardiac arrest or the presence of nonsustained ventricular tachycardia, or both).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cardiomiopatia Hipertrófica/fisiopatologia , Eletrocardiografia/métodos , Processamento de Sinais Assistido por Computador , Adolescente , Adulto , Idoso , Morte Súbita/etiologia , Ecocardiografia , Eletrocardiografia Ambulatorial , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
To assess the relation of exercise capacity to indexes of systolic and diastolic function in hypertrophic cardiomyopathy, 81 patients underwent two-dimensional echocardiography, technetium-99m equilibrium radionuclide angiography acquired in list mode and maximal, symptom-limited, treadmill exercise testing with measurement of maximal oxygen consumption (VO2 max). VO2 max for the group was 13.9 to 49.3 (mean 25.4) ml/min per kg. Thirty-six patients (44%) achieved less than or equal to 70% of age-predicted VO2 max. Patients with such a degree of limitation were more likely to be in New York Heart Association functional class II or III (23 of 36 vs. 14 of 45; p = 0.005); there was no such relation between VO2 and the incidence and magnitude of rest left ventricular outflow tract pressure gradient greater than 30 mm Hg (11 of 36 vs. 11 of 45; p = NS and 58 +/- 24 vs. 65 +/- 19 mm Hg; p = NS). In the 22 patients with a left ventricular outflow tract gradient, the ratios of peak ejection to peak filling rate and of atrial contribution to left atrial dimension were related to percent of the age-predicted VO2 max (r = 0.49, p = 0.02 and r = 0.54, p less than 0.02). These ratios reflect impaired left ventricular systolic performance and atrial systolic failure, respectively. Stepwise discriminant analysis revealed these two ratios to be the two strongest predictors (p = 0.0001) of patients with a left ventricular outflow tract gradient whose VO2 max was less than or equal to 70% of the age-predicted value (sensitivity 90%, specificity 100%).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cardiomiopatia Hipertrófica/fisiopatologia , Exercício Físico/fisiologia , Consumo de Oxigênio , Adulto , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico , Análise Discriminante , Ecocardiografia , Teste de Esforço , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Angiografia Cintilográfica , Sensibilidade e Especificidade , Função Ventricular Esquerda/fisiologia , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagem , Obstrução do Fluxo Ventricular Externo/etiologia , Obstrução do Fluxo Ventricular Externo/fisiopatologiaRESUMO
OBJECTIVES: First, we sought to study the effects of short- and long-term vitamin C therapy on oxidative stress and endothelial dysfunction in chronic heart failure (CHF), and second, we sought to investigate the role of neutrophils as a cause of oxidative stress in CHF. BACKGROUND: Oxidative stress may contribute to endothelial dysfunction in CHF. Vitamin C ameliorates endothelial dysfunction in CHF, presumably by reducing oxidative stress, but this is unproven. METHODS: We studied 55 patients with CHF (ischemic and nonischemic etiologies) and 15 control subjects. Flow-mediated dilation (FMD) in the brachial artery was measured by ultrasound wall-tracking, neutrophil superoxide anion (O2-) generation by lucigenin-enhanced chemiluminescence and oxidative stress by measurement of free radicals (FRs) in venous blood using electron paramagnetic resonance (EPR) spectroscopy and plasma thiobarbituric acid reactive substances (TBARS). Measurements were performed at baseline in all subjects. The effects of short-term (intravenous) and long-term (oral) vitamin C therapy versus placebo were tested in patients with nonischemic CHF. RESULTS: At baseline, FRs were higher in patients with CHF than in control subjects (p < 0.01), TBARS were greater (p < 0.005), neutrophil O2- -generating capacity was enhanced (p < 0.005) and FMD was lower (p < 0.0001). Compared with placebo, short-term vitamin C therapy reduced FR levels (p < 0.05), tended to reduce TBARS and increased FMD (p < 0.05), but did not affect neutrophil O2- -generating capacity. Long-term vitamin C therapy reduced FR levels (p < 0.05), reduced TBARS (p < 0.05) and improved FMD (p < 0.05), but also reduced neutrophil O2- -generating capacity (p < 0.05). Endothelial dysfunction was not related to oxidative stress, and improvements in FMD with vitamin C therapy did not relate to reductions in oxidative stress. CONCLUSIONS: Oxidative stress is increased in ischemic and nonischemic CHF, and neutrophils may be an important cause. Vitamin C reduces oxidative stress, increases FMD and, when given long term, decreases neutrophil O2- generation, but the lack of a correlation between changes in endothelial function and oxidative stress with vitamin C implies possible additional non-antioxidant benefits of vitamin C.
Assuntos
Ácido Ascórbico/uso terapêutico , Endotélio/fisiologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Neutrófilos/metabolismo , Estresse Oxidativo , Superóxidos/metabolismo , Ânions , Doença Crônica , Endotélio/efeitos dos fármacos , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fatores de TempoRESUMO
Post-prandial lipaemia (PPL) is a factor in atherogenesis and results in reversible endothelial dysfunction in healthy individuals. Oxidative stress and triglyceride (TG)-rich lipoproteins have been implicated. Type 2 diabetes (NIDDM) results in exaggerated PPL. We attempted to delineate the mechanisms of PPL induced, endothelial dysfunction (EF) and oxidative stress in 12 NIDDM and 12 matched healthy subjects. Subjects underwent a fat tolerance test, with endothelial function assessed by flow-mediated vasodilatation and oxidative stress measured by venous lipid-derived free radicals ex vivo and lipid peroxidation products over the postprandial phase. Fasting TG, post-prandial hypertriglyceridaemia and the TG enrichment of all lipoproteins was significantly greater in NIDDM. Post-prandial endothelial function inversely correlated with fasting HDL-C (r=-0.84, P=0.001) in both the control and NIDDM groups. The deterioration in EF in the NIDDM group also correlated with TG enrichment of VLDL and LDL. PPL in both groups also resulted in increased oxidative stress. The increment in free radicals correlated with TG enrichment of VLDL in both groups and was, therefore, greater in NIDDM. Thus, PPL -- with the production of TG-enrichment of VLDL -- results in endothelial dysfunction by an oxidative stress mechanism in both groups. The magnitude is greater in NIDDM. Fasting HDL-C appears to contribute to the protection of the endothelium against this phenomenon. Hence, exaggerated PPL associated with reduced HDL-C may be important in the pathogenesis of vascular disease, particularly in NIDDM.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Endotélio Vascular/fisiologia , Hiperlipidemias/sangue , Período Pós-Prandial , Adulto , Biomarcadores , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Hiperlipidemias/etiologia , Hiperlipidemias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Período Pós-Prandial/fisiologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Triglicerídeos/sangue , Ultrassonografia , VasodilataçãoRESUMO
OBJECTIVES: Controversy persists with regard to the atherogenic risk associated with adult growth hormone deficiency (GHD). Endothelial dysfunction and enhanced oxidative stress are early features of atherogenesis. Therefore, we have studied the effect of three months of low dose GH replacement therapy (0.03IU/kg/day) on these parameters in GHD adults. SUBJECTS AND METHODS: Eight hypopituitary GHD adults (4 male, 4 female), who were receiving conventional hormone replacement therapy, were studied before and after 3 months of GH replacement (0.03IU/kg/day). All observations obtained were compared with similar measurements made in 8 matched control subjects. All study subjects were non-smokers, normotensive and gave no personal or family history of premature vascular disease. Endothelial function was assessed using a specialised vessel wall tracking system to measure endothelium-dependent, flow-mediated, brachial artery dilatation (FMD). Measurements were repeated following glyceryl-trinitrate (GTN) (endothelium-independent dilatation). Oxidative stress was assessed by directly measuring lipid-derived free radicals in venous blood by electron paramagnetic resonance spectroscopy. Fasting lipids, insulin, plasma glucose and IGF-I were also measured at baseline and following GH replacement. RESULTS: FMD, expressed as a percentage change from resting base-line diameter, was significantly impaired in the pre-treatment GHD patients compared with controls (3.1+/-2.1% vs 6.1+/-0.9%, P<0. 001; means+/-s.d.) indicating endothelial dysfunction. Significant increase in FMD was noted following GH therapy (3.1+/-2.1% vs 6. 5+/-1.9%, P<0.001). Free radicals (arbitrary units) were elevated in the pre-treatment GHD patients compared with controls (0.36+/-0.09 vs 0.11+/-0.12, P<0.05) and fell significantly following GH therapy (0.23+/-0.03 vs 0.36+/-0.09, P<0.05), although they remained elevated compared with controls. Fasting insulin was significantly higher (25.9+/-18.8 vs 13.9+/-6.7mu/l, P<0.05) and IGF-I concentrations lower (10.8+/-4.7 vs 20.2+/-6.3nmol/l, P<0.05) in the pre-treatment GHD subjects. After treatment there were no changes in insulin concentration, although IGF-I levels were normalised (10. 8+/-2.3 vs 23.6+/-11.4nmol/l, P<0.05). CONCLUSIONS: Endothelial dysfunction and enhanced oxidative stress are features of adult GHD. This study suggests plausible mechanisms underlying any proatherogenic tendency in adult GHD and demonstrates improvement of these factors following GH replacement.
Assuntos
Endotélio Vascular/metabolismo , Hormônio do Crescimento/sangue , Hormônio do Crescimento/deficiência , Hipopituitarismo/sangue , Hipopituitarismo/tratamento farmacológico , Estresse Oxidativo , Adulto , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Estudos de Casos e Controles , Endotélio Vascular/fisiopatologia , Feminino , Radicais Livres/sangue , Hormônio do Crescimento/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
Augmentation of antioxidant defenses may help protect tissues against ischemia-reperfusion injury associated with operations involving cardiopulmonary bypass. In this study we examined the effect of pretreating patients with alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) or placebo on injury to the myocardium. Seventy-six subjects undergoing elective coronary artery bypass grafting participated in a prospective, double-blind, placebo-controlled randomized trial, receiving either placebo or both 750 IU dl-alpha-tocopherol per day for 7 to 10 days and 1 gm ascorbic acid 12 hours before the operation. Plasma alpha-tocopherol concentrations, raised fourfold by supplementation, fell by 70% after the operation in the supplemented group and to negligible levels in the placebo group. There were no significant differences between the groups with respect to release of creatine kinase MB isoenzyme over 72 hours, nor in the reduction of the myocardial perfusion defect determined by thallium 201 uptake. Electrocardiography provided no evidence of a benefit from antioxidant supplementation. Thus the supplementation regimen prevented the depletion of the primary lipid soluble antioxidant in plasma, but provided no measurable reduction in myocardial injury after the operation.
Assuntos
Ácido Ascórbico/farmacologia , Ponte de Artéria Coronária , Coração/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Pré-Medicação , Vitamina E/farmacologia , Adolescente , Adulto , Idoso , Ponte Cardiopulmonar , Creatina Quinase/sangue , Método Duplo-Cego , Feminino , Humanos , Isoenzimas , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Estudos Prospectivos , Radioisótopos de Tálio , Vitamina E/sangueRESUMO
Congestive heart failure (CHF) is associated with oxidative stress. Platelet responsiveness to nitric oxide (NO) donors, are impaired in patients with angina pectoris, possibly by increasing oxidative stress. We investigated the occurrence of platelet resistance to NO in patients, with ischaemic or non-ischaemic cardiomyopathy compared with normal subjects. Anti-aggregatory effects of sodium nitroprusside (SNP), oxidative stress and whole blood superoxide anion content were determined, with correlates of responsiveness to SNP. Inhibition of platelet aggregation by SNP was 65.4+/-3.55% in controls and 59.3+/-4.1% in CHF (P=ns) despite increased oxidative stress and post-aggregation O2- in CHF patients. However, subsets of CHF patients have NO-resistant platelets: this is associated with increasing age and/or increased oxidative stress (both p<0.05).
Assuntos
Insuficiência Cardíaca/fisiopatologia , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Estresse Oxidativo/fisiologia , Agregação Plaquetária/efeitos dos fármacos , Adulto , Fatores Etários , Idoso , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos de Casos e Controles , Técnicas de Cultura de Células , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
We evaluated the role of rest and exercise left ventricular diastolic filling parameters as a marker of cardiotoxicity in 25 consecutive patients 1 year following BMT. Ten age- and sex-matched subjects served as controls. Patients were evaluated in toto and in three sub-groups according to chemotherapy. Left ventricular ejection fraction (EF), peak filling rate (PFR) and time to peak filling (TTPF) were assessed at rest and at peak exercise. EF and PFR were similar at rest and at peak exercise in patients and controls. TTPF was significantly prolonged at rest in patients compared to controls (200 +/- 65 vs 131 +/- 26 ms, P = 0.003) and at peak exercise was markedly longer in patients (142 +/- 40 vs 54 +/- 19 ms, P < 0.001). Sub-group analysis demonstrated abnormal resting TTPF in those patients who had received either combination anthracycline and CY or anthracycline and melphalan, while those patients who received CY alone had normal resting TTPF. However, exercise TTPF was abnormally prolonged in all patient groups. While all controls demonstrated a normal decrease in TTPF during exercise, four of the 25 patients had a paradoxical increase in TTPF during exercise. Exercise diastolic function may provide evidence of cardiotoxicity in long-term survivors of BMT.