RESUMO
BACKGROUND: Increased sympathetic drive to the heart might contribute to the development and progression of myocardial damage in hypertensive patients (HTs). This study assessed the possible presence of abnormalities in myocardial uptake of (123)I-metaiodobenzylguanidine (MIBG), a marker of sympathetic activity, in HTs with left ventricular hypertrophy (LVH). METHODS: Eleven HTs with LVH and 10 matched normotensive controls underwent clinical and laboratory examination, as well as LVH determination by echocardiography. The presence of myocardial ischemia was ruled out by exercise stress testing. Global and regional myocardial uptake of (123)I-MIBG was determined in both groups using planar and single proton emission tomography scintigraphy. In addition, thallium-201 (Tl-201) myocardial scintigraphy was performed in HTs. The heart/mediastinum (H/M) ratio on planar (123)I-MIBG images at different time points was compared between HTs and controls. Moreover, regional cardiac uptake of (123)I-MIBG was compared between groups and, within the HTs group, with regional Tl-201 uptake. RESULTS: At all study times, the H/M ratio was lower in HTs than in controls (all p <0.05). A significant reduction in (123)I-MIBG uptake in the mid-inferolateral and mid-inferior segments was observed in HTs compared to controls. Also, a significant reduction in (123)I-MIBG uptake compared to Tl-210 uptake was observed in non-septal segments of HTs. CONCLUSIONS: Cardiac abnormalities in global and regional uptake of (123)I-MIBG, as well as impaired (123)I-MIBG compared to Tl-201 uptake, are present in HTs with LVH. Given the effect of sympathetic nervous system on the heart, these abnormalities might play a role in hypertension-related cardiac damage.
Assuntos
Hipertensão/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Sistema Nervoso Simpático/diagnóstico por imagem , 3-Iodobenzilguanidina , Ecocardiografia , Feminino , Coração , Humanos , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/fisiopatologia , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico por imagem , Cintilografia , Radioisótopos de TálioRESUMO
BACKGROUND: Metabolic syndrome importantly accelerates the atherosclerotic process, the earliest event of which is endothelial dysfunction. Ghrelin, a gastric peptide with cardiovascular actions, has been shown to inhibit proatherogenic changes in experimental models. This study therefore investigated whether ghrelin administration might beneficially affect endothelial function in metabolic syndrome. METHODS AND RESULTS: Endothelium-dependent and -independent vasodilator responses to intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside (SNP), respectively, were assessed by strain-gauge plethysmography before and after local administration of human ghrelin (200 microg/min). During saline, the vasodilator response to acetylcholine was significantly blunted (P=0.008) in patients with metabolic syndrome (n=12, 5 female) compared with controls (n=12, 7 female), whereas the vasodilator response to SNP was not different between groups (P=0.68). In patients with metabolic syndrome, basal plasma ghrelin was significantly lower than in controls (P=0.02). In these patients, ghrelin infusion markedly increased intravascular concentrations of the peptide (P<0.001) and resulted in a potentiation of the vasodilator response to acetylcholine (P=0.001 versus saline) but not to SNP (P=0.22). This effect was likely related to enhanced nitric oxide bioavailability because, in a group of patients with metabolic syndrome (n=6, 2 female), ghrelin had no effect on the vasodilator response to acetylcholine (P=0.78 versus saline) after nitric oxide inhibition by NG-monomethyl-L-arginine. CONCLUSIONS: These findings indicate that ghrelin reverses endothelial dysfunction in patients with metabolic syndrome by increasing nitric oxide bioactivity, thereby suggesting that decreased circulating levels of the peptide, such as those found in these patients, might play a role in the pathobiology of atherosclerosis.
Assuntos
Endotélio Vascular/fisiopatologia , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/fisiopatologia , Hormônios Peptídicos/uso terapêutico , Acetilcolina/farmacologia , Adulto , Endotélio Vascular/efeitos dos fármacos , Feminino , Grelina , Intolerância à Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Nitroprussiato/farmacologia , Obesidade/complicações , Valores de Referência , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia , Vasodilatadores/farmacologiaRESUMO
BACKGROUND: Patients with rheumatoid arthritis (RA) have endothelial dysfunction, which may predispose them to the risk of premature atherosclerosis. This study investigated the involvement of tumor necrosis factor (TNF) alpha in the pathophysiologic characteristics of this abnormality by use of the TNF-alpha-neutralizing antibody infliximab. METHODS: Endothelium-dependent and -independent vasodilator responses to intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside, respectively, were assessed by strain-gauge plethysmography in patients (n = 10) with early RA during saline solution infusion and after intra-arterial infusion of infliximab (200 microg/min). RESULTS: Circulating markers of systemic inflammation (C-reactive protein and interleukin 6) were higher in patients than in control subjects (n = 10, both P < .05), whereas plasma levels of TNF-alpha and soluble TNF receptor types 1 and 2 were similar in both groups (all P > .05). During saline solution infusion, the vasodilator response to acetylcholine was blunted in patients with RA compared with control subjects (14.2 +/- 9.2 mL . min-(1). dL-(1) versus 23.7 +/- 9.2 mL . min-(1). dL-(1) at the highest dose, P = .004) whereas vasodilation to sodium nitroprusside was not different between groups (P = .10). In patients with RA infliximab did not modify circulating C-reactive protein levels (P = .29, versus saline solution) but did potentiate the vasodilator response to acetylcholine (21.0 +/- 11.1 mL . min-(1). dL-(1); P = .004, versus saline solution). The response to sodium nitroprusside, in contrast, was not modified by infliximab (P = .28 versus saline solution). CONCLUSIONS: Intravascular administration of anti-TNF-alpha antibody ameliorates endothelial function in patients with RA but does not concurrently affect systemic inflammatory changes. Our findings suggest that enhanced TNF-alpha generation within the vessel wall, rather than systemic mechanisms, plays a role in the pathobiologic features of endothelial dysfunction in RA.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Acetilcolina/farmacologia , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacocinética , Antirreumáticos/administração & dosagem , Antirreumáticos/farmacocinética , Antirreumáticos/uso terapêutico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/fisiopatologia , Proteína C-Reativa/metabolismo , Relação Dose-Resposta a Droga , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Infliximab , Infusões Intra-Arteriais , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Nitroprussiato/farmacologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Vasodilatação/efeitos dos fármacosRESUMO
OBJECTIVE: Impaired endothelium-dependent vasodilator function may contribute to vascular damage in patients with systemic sclerosis (SSc). This study was undertaken to investigate whether increased activity of the endothelin 1 (ET-1) system plays a role in the occurrence of endothelial dysfunction in patients with SSc. METHODS: In 12 patients with SSc (6 with diffuse cutaneous SSc [dcSSc] and 6 with limited cutaneous SSc [lcSSc]), forearm blood flow responses to graded doses of acetylcholine (ACh) and sodium nitroprusside (SNP) given intraarterially were assessed by plethysmography, during infusion of saline and following selective blockade of ETA receptors with BQ-123 (10 nmoles/minute). RESULTS: During saline infusion, the vasodilator response to ACh was blunted in patients with SSc as compared with that in healthy controls (P<0.001), whereas the response to SNP was not different between groups (P=0.27). The vasodilator effect of ETA receptor antagonism was higher in patients than in controls (P<0.001), indicating enhanced ET-1-mediated vasoconstriction in SSc. In patients, ETA receptor blockade resulted in a potentiation of the vasodilator response to ACh (P<0.001 versus saline), but did not affect the response to SNP (P=0.31). Notably, both the vasodilator effect of ETA receptor antagonism and the improvement in the responsiveness to ACh following BQ-123 infusion were higher in patients with dcSSc than in those with lcSSc (P<0.01). CONCLUSION: ET-1-dependent vasoconstrictor tone is increased predominantly in the subgroup of SSc patients with dcSSc, in whom acute blockade of ETA receptors was able to improve impaired endothelium-dependent vasodilator function. Our results suggest novel vasculoprotective effects of ETA receptor antagonism and support further exploration of strategies that target the ET-1 pathway in SSc.
Assuntos
Anti-Hipertensivos/farmacologia , Antagonistas do Receptor de Endotelina A , Endotélio Vascular/fisiopatologia , Peptídeos Cíclicos/farmacologia , Escleroderma Sistêmico/fisiopatologia , Acetilcolina/administração & dosagem , Acetilcolina/farmacologia , Adulto , Anti-Hipertensivos/administração & dosagem , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Endotelina-1/fisiologia , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Nitroprussiato/administração & dosagem , Nitroprussiato/farmacologia , Peptídeos Cíclicos/administração & dosagem , Pletismografia , Receptor de Endotelina A/efeitos dos fármacos , Receptor de Endotelina A/fisiologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia , Vasodilatadores/administração & dosagem , Vasodilatadores/farmacologiaRESUMO
OBJECTIVE: Obesity is associated with chronic inflammation due to overproduction of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha. We assessed the effects of TNF-alpha neutralization by infliximab on vascular reactivity during hyperinsulinemia in obesity-related metabolic syndrome. RESEARCH DESIGN AND METHODS: Vascular responses to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in patients with metabolic syndrome, before and after administration of infliximab. RESULTS: Patients had blunted vasodilator responses to ACh and SNP during hyperinsulinemia compared with control subjects; a potentiation of the responsiveness to both ACh and SNP, however, was observed in patients following infliximab. The antioxidant vitamin C improved the vasodilator response to ACh in patients with metabolic syndrome, but its effect was not further enhanced by concurrent administration of infliximab. CONCLUSIONS: TNF-alpha neutralization ameliorates vascular reactivity in metabolic syndrome during hyperinsulinemia, likely in relation to decreased oxidative stress, thereby suggesting an involvement of inflammatory cytokines in vascular dysfunction of these patients.
Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Hiperinsulinismo/fisiopatologia , Síndrome Metabólica/fisiopatologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Análise de Variância , Glicemia/metabolismo , Colesterol/sangue , Humanos , Hiperinsulinismo/tratamento farmacológico , Infliximab , Síndrome Metabólica/tratamento farmacológico , Nitroprussiato/farmacologia , Valores de Referência , Triglicerídeos/sangueRESUMO
OBJECTIVES: This investigation was undertaken to compare diabetic and non-diabetic hypertensive patients with a first acute non-ST segment elevation myocardial infarction (NSTEMI) and to assess the impact of clinical and laboratory parameters on the occurrence of in-hospital complications. METHODS: The study population comprised 112 consecutive male hypertensive patients with their first NSTEMI, who were divided into two groups according to the presence of type 2 diabetes mellitus. All patients underwent echocardiography and 24-h electrocardiographic (ECG) and blood pressure monitoring within 48 h from admission. RESULTS: Diabetic hypertensive patients had significantly higher mean daytime, night-time, 24-h systolic blood pressure and heart rate and hypertensive peaks (P < 0.01), more episodes of asymptomatic ST segment depression (P < 0.05), which were also more severe and prolonged (P < 0.01), and more episodes of non-sustained ventricular tachycardia (P = 0.01). Diabetic patients showed a greater left ventricular mass index (LVMI) and a lower left ventricular ejection fraction (LVEF) (P < 0.01). In-hospital adverse clinical events were more frequent in diabetic hypertensives compared to non-diabetics (40.3% versus 18.1%, P = 0.01). In particular, heart failure occurred during hospitalization in 33.3% versus 14.5% (P = 0.02). The difference in transient cerebral ischaemic attacks did not reach statistical significance (7.0% versus 1.8%, P = 0.18). Multivariate Cox proportional hazards analysis showed that the only independent predictors for the occurrence of in-hospital adverse clinical events in diabetic patients were: 24-h systolic blood pressure variability [relative risk (RR) = 1.013, 95% confidence interval (CI) = 1.001-1.025, P = 0.03]; mean 24-h heart rate (RR = 7.05, 95% CI = 1.35-35.9, P = 0.02) and the LVMI (RR = 1.9, 95% CI = 1.121-3.785, P = 0.02). CONCLUSIONS: This study indicates that in-hospital complications, including heart failure and transient cerebral ischaemia, occur frequently during the acute phase of a first NSTEMI in patients with both diabetes and hypertension. The coexistence of diabetes and hypertension doubles the risk of complications with respect to hypertension alone. In addition, adverse events may appear despite an initial uncomplicated clinical presentation, which can be predicted by the early assessment of heart rate and blood pressure behaviour and by the echocardiographic assessment of left ventricular mass.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Eletrocardiografia Ambulatorial , Insuficiência Cardíaca/etiologia , Hipertensão/complicações , Pacientes Internados , Ataque Isquêmico Transitório/etiologia , Infarto do Miocárdio/complicações , Pressão Sanguínea/fisiologia , Intervalos de Confiança , Diabetes Mellitus Tipo 2/epidemiologia , Ecocardiografia , Seguimentos , Insuficiência Cardíaca/epidemiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Incidência , Ataque Isquêmico Transitório/epidemiologia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Patients with renovascular hypertension (RVH) have a higher degree of cardiovascular end-organ damage compared to patients with essential hypertension (EH). The precise mechanisms underlying this phenomenon, however, have not been fully elucidated. This study investigated the relationship between circadian blood pressure (BP) profile and cardiac involvement in patients with RVH and EH. METHODS: Twenty patients with RVH and 20 with EH, matched for demographic characteristics, underwent simultaneous 24-hour ambulatory BP recording and Holter ECG monitoring. Also, each participant underwent echocardiographic assessment of left ventricular mass. Cardiac damage was defined as the presence of left ventricular hypertrophy, myocardial ischemia or arrhythmias. RESULTS: Casual BP was similar in both groups, whereas 24-hour ambulatory BP values were higher in RVH than in EH patients; moreover, RVH patients had higher blood pressure variability and blunted nocturnal BP fall compared to those with EH. Left ventricular mass, as well as the prevalence of myocardial ischemia and the presence and severity of cardiac arrhythmias, were higher in RVH than in EH patients. CONCLUSIONS: Patients with RVH have altered circadian BP profile compared to those with EH. This abnormality might contribute to their increased prevalence of cardiac damage and might adversely affect the prognosis of these patients.
Assuntos
Hipertensão Renovascular/diagnóstico , Hipertrofia Ventricular Esquerda/etiologia , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano , Ecocardiografia Doppler , Eletrocardiografia Ambulatorial , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão Renovascular/epidemiologia , Hipertrofia Ventricular Esquerda/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Probabilidade , Estudos Prospectivos , Medição de Risco , Estudos de Amostragem , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
AIMS: Aim of the present study was the development and the subsequent validation of a simple risk classification system for patients presenting with syncope to the emergency departments. METHODS AND RESULTS: A group of 270 consecutive patients (145 females, mean age 59.5 years) presenting with syncope to the emergency departments of six community hospitals of the Lazio region of Italy was used as a derivation cohort for the development of the risk classification system. Data from the baseline clinical history, physical examination and electrocardiogram were used to identify independent predictors of total mortality within the first 12 months after the initial evaluation. Multivariate analysis allowed the recognition of the following predictors of mortality: (1) age >65 years; (2) cardiovascular disease in clinical history; (3) syncope without prodromes; and (4) abnormal electrocardiogram. The OESIL (Osservatorio Epidemiologico sulla Sincope nel Lazio) score was calculated by the simple arithmetic sum of the number of predictors present in every single patient. Mortality increased significantly as the score increased in the derivation cohort (0% for a score of 0, 0.8% for 1 point; 19.6% for 2 points; 34.7% for 3 points; 57.1% for 4 points; p<0,0001 for trend). A similar pattern of increasing mortality with increasing score was prospectively confirmed in a second validation cohort of 328 consecutive patients (178 females; mean age, 57.5 years). CONCLUSIONS: Clinical and electrocardiographic data available at presentation to the emergency department can be used for the risk stratification of patients with syncope. The OESIL risk score may represent a simple prognostication tool that could be usefully employed for the triage and management of patients with syncope in emergency departments.