RESUMEN
BACKGROUND: Blood-activating drugs (BADs) are widely used to treat microvascular angina in China. This study aims to summarize relevant evidence from randomized controlled trials (RCTs) to assess the efficacy and safety of BADs in the treatment of microvascular angina. METHODS: We searched for relevant studies before June 2019 from seven databases. Twenty-four studies were included of 1903 patients with microvascular angina. All studies compared the use of traditional Chinese medicine for activating blood circulation (BADs) and Western medicine (WM) with the use of Western medicine alone. RESULTS: In all, 15 trials reported a significant effect of BADs on improving clinical symptoms compared with the control treatment (Pâ¯<â¯.00001), and 8 trials reported significant effects of BADs on reducing the frequency of angina pectoris attacks compared with Western medicine treatment (Pâ¯<â¯.00001). The pooled results also demonstrated that BADs provided a significant benefit in reducing the dosage of nitroglycerin required (Pâ¯=â¯.02), the maximum range of ST-segment depression (Pâ¯=â¯.003) and the descending degree of the ST-T segment of ECG (Pâ¯=â¯.0002); prolonging the total time of treadmill exercise (Pâ¯<â¯.00001) and the time of ST-segment depression of 1â¯mm (Pâ¯=â¯.002); enhancing the total effective rate of Traditional Chinese Medicine (TCM) syndromes (Pâ¯<â¯.00001); improving endothelial function (Pâ¯<â¯.00001); and reducing the levels of high-sensitivity C-reactive protein (hs-CRP) (Pâ¯<â¯.00001). BAD treatment showed no statistically significant effect on the levels of TNF-a (P = .8) or IL-6 (Pâ¯=â¯.13). No severe adverse events were reported. CONCLUSION: This meta-analysis shows that BADs are effective for the treatment of microvascular angina. Although concerns regarding selective bias and low methodological quality were raised, our findings suggest that BADs are beneficial for patients with microvascular angina and should be given priority for future clinical studies.
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Medicamentos Herbarios Chinos/uso terapéutico , Angina Microvascular/tratamiento farmacológico , Proteína C-Reactiva/metabolismo , Endotelina-1/metabolismo , Prueba de Esfuerzo , Humanos , Interleucina-6/metabolismo , Medicina Tradicional China , Angina Microvascular/metabolismo , Angina Microvascular/fisiopatología , Óxido Nítrico/metabolismo , Nitroglicerina/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismo , Vasodilatadores/administración & dosificaciónRESUMEN
Background Soluble urokinase plasminogen activator receptor (su PAR ) is a proinflammatory biomarker associated with immune activation and fibrinolysis inhibition. Plasminogen activator inhibitor ( PAI -1) is associated with excessive fibrin accumulation, thrombus formation, and atherosclerosis. The relationship between cross-coronary su PAR and PAI -1 production and endothelial dysfunction remains unknown. Methods and Results Seventy-nine patients (age 53±10 years, 75% women) with angina and normal coronary arteries or mild coronary artery disease (<40% stenosis) on angiogram underwent acetylcholine assessment of epicardial endothelial dysfunction (mid-left anterior descending coronary artery diameter decrease >20% after acetylcholine) and mircovascular endothelial dysfunction (coronary blood flow change <50% after acetylcholine). Simultaneous left main and coronary sinus su PAR and PAI -1 levels were measured in each patient before acetylcholine administration, and cross-coronary su PAR and PAI -1 production rates were calculated. Patients' characteristics, except for age (51±10 versus 57±9, P=0.02), and resting coronary hemodynamics were not significantly different between patients with (26%) versus without (74%) epicardial endothelial dysfunction. Patients' characteristics and resting coronary hemodynamics were not significantly different between those with (62%) and those without (38%) mircovascular endothelial dysfunction. Patients with mircovascular endothelial dysfunction demonstrated local coronary su PAR production versus su PAR extraction in patients with normal microvascular function (median 25.8 [interquartile range 121.6, -23.7] versus -12.7 [52.0, -74.8] ng/min, P=0.03). Patients with epicardial endothelial dysfunction had higher median coronary PAI -1 production rates compared with those with normal epicardial endothelial function (1224.7 [12 940.7, -1915.4] versus -187.4 [4444.7, -4535.8] ng/min, P=0.03). Conclusions su PAR is released in coronary circulation of patients with mircovascular endothelial dysfunction and extracted in those with normal microvascular function. Cross-coronary PAI -1 release is higher in humans with epicardial endothelial dysfunction.
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Vasos Coronarios/fisiopatología , Endotelio Vascular/fisiopatología , Microvasos/fisiopatología , Inhibidor 1 de Activador Plasminogénico/metabolismo , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Adulto , Angiografía Coronaria , Circulación Coronaria , Vasos Coronarios/metabolismo , Endotelio Vascular/metabolismo , Femenino , Humanos , Masculino , Angina Microvascular/metabolismo , Angina Microvascular/fisiopatología , Microvasos/metabolismo , Persona de Mediana EdadRESUMEN
Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the association of CYP2C19 polymorphisms and EETs on microvascular angina (MVA) caused by coronary microvascular dysfunction. We examined CYP2C19 genotypes in patients with MVA (n = 71) and healthy subjects as control (n = 71). MVA was defined as the absence of coronary artery stenosis and epicardial spasms and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphosphate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of-functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite. MVA group showed significantly higher CYP2C19 PM incidence (35% vs. 16%; P = 0.007) and high sense C-reactive protein (hs-CRP) levels (0.127 ± 0.142 vs. 0.086 ± 0.097 mg/dl; P = 0.043) than those of controls. Moreover, in MVA group, hs-CRP levels in CYP2C19 PM were significantly higher than that of non-PM (0.180 ± 0.107 vs. 0.106 ± 0.149 mg/dl, P = 0.045). Multivariate analysis indicated that smoking, hypertension, high hs-CRP, and CYP2C19 PM are predictive factors for MVA. In MVA group, DHET levels for CYP2C19 PM were significantly lower than that of non-PM [10.9 ± 1.64 vs. 14.2 ± 5.39 ng/ml, P = 0.019 (11,12-DHET); 15.2 ± 4.39 vs. 17.9 ± 4.73 ng/ml, P = 0.025 (14,15-DHET)]. CYP2C19 variants are associated with MVA. The decline of EET-based defensive mechanisms owing to CYP2C19 variants may affect coronary microvascular dysfunction.
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Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Proteína C-Reactiva/metabolismo , Citocromo P-450 CYP2C19/genética , Ácidos Hidroxieicosatetraenoicos/metabolismo , Angina Microvascular/genética , Ácido 8,11,14-Eicosatrienoico/metabolismo , Anciano , Ácido Araquidónico/metabolismo , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hipertensión/epidemiología , Modelos Logísticos , Masculino , Angina Microvascular/epidemiología , Angina Microvascular/metabolismo , Persona de Mediana Edad , Análisis Multivariante , Polimorfismo Genético , Factores de Riesgo , Fumar/epidemiologíaRESUMEN
OBJECTIVE: Cardiac X syndrome is defined in patients with normal coronary angiogram who has typical chest pain and objective myocardial ischemia evidence. Recent studies have evaluated the association between vitamin D deficiency (vit D def) and cardiovascular diseases. Our aim of this study was to compare serum vit D levels in patients with syndrome X and controls. PATIENTS AND METHODS: We included 66 patients (49 women, 17 men) with syndrome X and 47 (30 women, 17 men) healthy controls. All of the patients' demographic features, laboratory analysis and medications are recorded. Vit D is measured quantitatively by paramagnetic particle chemiluminescence method. RESULTS: Mean age of the syndrome X group was higher than controls (56 ± 9.2 vs. 49 ± 9.6 years p < 0.001). Body mass index was higher in the patient group than controls (31.2 ± 5.6 vs. 29.1 ± 4.7 kg/m2 p: 0.011). Vit D levels were significantly lower in the syndrome X group than controls (6 ± 5.2 vs. 11.9 ± 7 ng/ml, p < 0.001). Parathormone levels were significantly higher in the syndrome X group than the control group (38.3 ± 23.4 vs. 28 ± 17.2 pg/ml, p: 0.014). hsCRP levels were higher in the syndrome X group than controls (3.1 ± 5.4 vs. 1.8 ± 2.4 mg/L, p: 0.042). CONCLUSIONS: Our study demonstrated significantly lower vit D levels in patients with CSX. This finding is correlated with previous studies showing an inverse correlation with lower serum vit D levels and different types of cardiovascular diseases. Vit D def may be a risk factor for syndrome X. Vit D def related increased inflammation may lead to the development of endothelial dysfunction and microvascular angina.
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Angina Microvascular/metabolismo , Deficiencia de Vitamina D/sangre , Vitamina D/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVES: Cardiac syndrome X (CSX) is a condition characterized by exercise-induced chest pain that occurs considering a normal coronary angiogram. We aimed to investigate the total serum antioxidant capacity (TAC) and biventricular global functions using echocardiography in patients with CSX. PATIENTS AND METHODS: The study population included 55 patients with typical anginal symptoms and a positive exercise stress test, or ischemia in myocardial perfusion scintigraphy and normal coronary arteries detected angiographically, and 49 healthy volunteers with atypical chest pain and a negative stress test. TAC was assessed from blood samples. Transthoracic echocardiography was performed for the entire study population. The Tei index was calculated using the formula IVCT+IVRT/ET. RESULTS: TAC was found to be significantly lower in the CSX group compared with the control group (0.70±0.37 vs. 1.5±0.30, respectively, P<0.001). The Tei index was significantly higher in patients with CSX than the control group (0.60±0.18 vs. 0.42±0.12, respectively, P<0.001).There was a significant and inverse relationship between TAC and the Tei index (r=-0.41, P<0.001). When we divided the study population according to the normal range of TAC into the decreased TAC group (<1.30 mmol/l), the normal TAC group (1.30-1.77 mmol/l), and the increased TAC group (>1.77 mmol/l), it was found that the Tei index was higher in the decreased TAC group compared with the other groups (0.66±0.18 vs. 0.49±0.10 and 0.46±0.13 mmol/l, P<0.001, respectively). CONCLUSION: Our study suggested that TAC was significantly decreased in CSX patients and decreased antioxidant levels were related to impaired Tei index in echocardiography in patients with microvascular angina.
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Antioxidantes/metabolismo , Angina Microvascular/metabolismo , Contracción Miocárdica/fisiología , Estrés Oxidativo , Adulto , Estudios de Casos y Controles , Angiografía Coronaria , Ecocardiografía Doppler , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Angina Microvascular/diagnóstico , Angina Microvascular/fisiopatología , Persona de Mediana Edad , Imagen de Perfusión Miocárdica , Factores de TiempoRESUMEN
A decreased nitric oxide (NO) bioavailability and an increased oxidative stress play a pivotal role in different cardiovascular pathologies. As red blood cells (RBCs) participate in NO formation in the bloodstream, the aim of this study was to outline the metabolic profile of L-arginine (Arg)/NO pathway and of oxidative stress status in RBCs and in plasma of patients with microvascular angina (MVA), investigating similarities and differences with respect to coronary artery disease (CAD) patients or healthy controls (Ctrl). Analytes involved in Arg/NO pathway and the ratio of oxidized and reduced forms of glutathione were measured by LC-MS/MS. The arginase and the NO synthase (NOS) expression were evaluated by immunofluorescence staining. RBCs from MVA patients show increased levels of NO synthesis inhibitors, parallel to that found in plasma, and a reduction of NO synthase expression. When summary scores were computed, both patient groups were associated with a positive oxidative score and a negative NO score, with the CAD group located in a more extreme position with respect to Ctrl. This finding points out to an impairment of the capacity of RBCs to produce NO in a pathological condition characterized mostly by alterations at the microvascular bed with no significant coronary stenosis.
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Glutatión/análisis , Angina Microvascular/diagnóstico , Óxido Nítrico/metabolismo , Estrés Oxidativo , Adulto , Anciano , Arginina/metabolismo , Cromatografía Líquida de Alta Presión , Enfermedad de la Arteria Coronaria/metabolismo , Enfermedad de la Arteria Coronaria/patología , Eritrocitos/enzimología , Eritrocitos/metabolismo , Femenino , Humanos , Masculino , Angina Microvascular/metabolismo , Angina Microvascular/patología , Persona de Mediana Edad , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Espectrometría de Masas en TándemAsunto(s)
Fármacos Cardiovasculares/uso terapéutico , Angiografía Coronaria/métodos , Vasos Coronarios/fisiopatología , Endotelio Vascular/metabolismo , Angina Microvascular , Dolor en el Pecho/metabolismo , Dolor en el Pecho/fisiopatología , Costo de Enfermedad , Manejo de la Enfermedad , Endotelio Vascular/efectos de los fármacos , Humanos , Angina Microvascular/diagnóstico , Angina Microvascular/epidemiología , Angina Microvascular/etiología , Angina Microvascular/metabolismo , Angina Microvascular/fisiopatología , Angina Microvascular/terapia , Prevalencia , Pronóstico , Factores SexualesRESUMEN
BACKGROUND: The pathophysiology of chest pain in patients with cardiac syndrome X remains controversial. Advances in perfusion imaging with cardiovascular magnetic resonance (CMR) now enable absolute quantification of regional myocardial blood flow (MBF). Furthermore, blood oxygen level-dependent (BOLD) or oxygenation-sensitive CMR provides the unprecedented capability to assess regional myocardial oxygenation. We hypothesized that the combined assessment of regional perfusion and oxygenation with CMR could clarify whether patients with syndrome X show evidence of myocardial ischemia (reduced perfusion and oxygenation) during vasodilator stress compared with normal volunteers. METHODS AND RESULTS: Eighteen patients with syndrome X (chest pain, abnormal exercise treadmill test, normal coronary angiogram without other causes of microvascular dysfunction) and 14 controls underwent CMR scanning at 3 T. Myocardial function, scar, perfusion (2-3 short-axis slices), and oxygenation were assessed. Absolute MBF was measured during adenosine stress (140 µg/kg per minute) and at rest by model-independent deconvolution. For oxygenation, using a T2-prepared BOLD sequence, signal intensity was measured at adenosine stress and rest in the slice matched to the midventricular slice of the perfusion scan. There were no significant differences in MBF at stress (2.35 versus 2.37 mL/min per gram; P=0.91), BOLD signal change (17.3% versus 17.09%; P=0.91), and coronary flow reserve measurements (2.63 versus 2.53; P=0.60) in patients with syndrome X and controls, respectively. Oxygenation and perfusion measurements per coronary territory were also similar between the 2 groups. More patients with syndrome X (17/18 [94%]) developed chest pain during adenosine stress than controls (6/14 [43%]; P=0.004). CONCLUSIONS: Patients with syndrome X show greater sensitivity to chest pain compared with controls but no evidence of deoxygenation or hypoperfusion during vasodilatory stress.
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Circulación Coronaria , Imagen por Resonancia Magnética , Angina Microvascular/diagnóstico , Imagen de Perfusión Miocárdica/métodos , Miocardio/metabolismo , Consumo de Oxígeno , Adenosina , Anciano , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Medios de Contraste , Inglaterra , Femenino , Gadolinio DTPA , Hemodinámica , Humanos , Modelos Lineales , Masculino , Angina Microvascular/metabolismo , Angina Microvascular/patología , Angina Microvascular/fisiopatología , Persona de Mediana Edad , Miocardio/patología , Dimensión del Dolor , Valor Predictivo de las Pruebas , VasodilatadoresRESUMEN
Since initial reports over 4 decades ago, cases of patients with angina-like chest pain whose coronary angiograms show no evidence of obstructive coronary artery disease and who have no structural heart disease continue to be a common occurrence for cardiologists. Many features of this patient population have remained constant with successive reports over time: a female predominance, onset of symptoms commonly between 40 and 50 years of age, pain that is severe and disabling, and inconsistent responses to conventional anti-ischemic therapy. Because patients may have had abnormal noninvasive testing that led to performance of coronary angiography, investigators have sought to show an association of this syndrome with myocardial ischemia. Abnormalities in coronary flow and metabolic responses to stress have been reported by several groups, findings consistent with a microvascular etiology for ischemia and symptoms, but others have questioned the presence of ischemia, even in patients selected for abnormal noninvasive testing. Despite considerable efforts by many groups over 4 decades, the syndrome remains controversial with regard to pathophysiology, diagnosis, and management.
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Dolor en el Pecho/diagnóstico por imagen , Angiografía Coronaria , Angina Microvascular/fisiopatología , Adulto , Animales , Enfermedad de la Arteria Coronaria/metabolismo , Circulación Coronaria , Vasos Coronarios/metabolismo , Endotelio Vascular/fisiopatología , Femenino , Humanos , Microcirculación , Angina Microvascular/diagnóstico por imagen , Angina Microvascular/metabolismo , Angina Microvascular/terapia , Persona de Mediana Edad , Isquemia Miocárdica , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Factores de Riesgo , Función Ventricular Izquierda , omega-N-Metilarginina/farmacologíaRESUMEN
INTRODUCTION: We previously showed that platelet reactivity at rest is increased in patients with cardiac syndrome X (CSX), but that exercise reduces platelet reactivity in these patients. Adenosine was suggested to be involved in this phenomenon. In this study we investigated the effect of adenosine on adenosine diphosphate (ADP) and thrombin-induced platelet reactivity in CSX patients. MATERIALS AND METHODS: We studied 15 CSX patients and a control group of 15 healthy subjects. Formation of monocyte-platelet (MONO-PLT) aggregates in vitro was assessed by flow cytometry: 1) at baseline; 2) after ADP (10(-7) M) stimulation alone; 3) after ADP stimulation in presence of adenosine (10(-5) M); 4) after thrombin (10(-11) M) stimulation alone; 5) after thrombin stimulation in presence of adenosine. RESULTS: In non stimulated samples there were no relevant differences between the two groups in cytometry variables. Compared to controls, ADP induced a higher increase in MONO-PLT aggregates in CSX patients (P < 0.01), which was significantly inhibited by adenosine (P < 0.01). Thrombin also induced a greater increase in MONO-PLT aggregates in CSX patients (P < 0.001), which was also significantly blunted by adenosine. Similar trends were observed for platelet CD41 (glycoprotein IIb-IIIa) receptor and for monocyte receptors CD142 ad CD162 in MONO-PLT aggregates. CONCLUSIONS: In CSX patients platelet reactivity is increased at rest, compared to healthy controls. Pre-incubation with adenosine reduces the agonist-induced platelet hyper-reactivity in these patients, suggesting that adenosine may be involved in the reduction of platelet reactivity observed in CSX patients after exercise in our previous study.
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Adenosina Difosfato/antagonistas & inhibidores , Adenosina/farmacología , Monocitos/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Trombina/farmacología , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Plaquetas/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Angina Microvascular/diagnóstico , Angina Microvascular/metabolismo , Persona de Mediana Edad , Selectina-P/metabolismo , Tromboplastina/metabolismo , Factores de TiempoRESUMEN
Morbidity of patients with cardiac syndrome X (typical anginal-like chest pain and normal coronary arteriogram) is high with continuing episodes of chest pain and frequent hospital readmissions. Management of this syndrome represents a major challenge for the treating physician. Conventional therapies with antianginal agents such as nitrates, calcium channel antagonists, classic beta-adrenoceptor blockers and nicorandil have been tried, with variable success. However, this might be related to a failure to target the underlying pathophysiology and, clearly, more effective therapies are needed. Supporting evidence for the important role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X has come from the recent observation that basal superoxide production predicts future cardiovascular events in this patient group. This review will discuss the pathophysiology, current medical management and potential new pharmacological treatment for patients with cardiac syndrome X which target endothelial dysfunction and oxidative stress. What's already known about this topic? Morbidity of patients with cardiac syndrome X is high. The important role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X. What does this article add? This review will discuss the pathophysiology, current medical management and potential new pharmacological treatment for patients with cardiac syndrome X which target endothelial dysfunction and oxidative stress.
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Antioxidantes/uso terapéutico , Fármacos Cardiovasculares/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Angina Microvascular/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Animales , Terapia Cognitivo-Conductual , Endotelio Vascular/fisiopatología , Terapia de Reemplazo de Estrógeno , Estrógenos/deficiencia , Ejercicio Físico , Humanos , Inflamación/metabolismo , Inflamación/fisiopatología , Inflamación/terapia , Resistencia a la Insulina , Microcirculación/efectos de los fármacos , Angina Microvascular/metabolismo , Angina Microvascular/fisiopatología , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/terapia , Resultado del TratamientoRESUMEN
OBJECTIVE: To assess whether abnormalities in cardiac uptake of (123)I-metaiodobenzylguanidine (MIBG) correlate with coronary microvascular dysfunction in patients with cardiac syndrome X (CSX). SETTING: University hospital. PATIENTS: 29 patients (aged 59 (SD 7) years, 11 men) with typical CSX and a matched group of 20 healthy subjects (aged 56 (7) years, 8 men) were studied. INTERVENTIONS: Planar and single photon emission computed tomography (SPECT) MIBG myocardial scintigraphy was performed in all subjects. Coronary flow response (CFR) to adenosine and to cold pressor test (CPT) in the left anterior descending (LAD) coronary artery was assessed in all CSX patients and in 12 controls by transthoracic Doppler echocardiography. MAIN OUTCOME MEASURES: Abnormalities in cardiac MIBG scintigraphy were observed in 25 CSX patients (86.2%), but in no healthy control (p<0.001). Compared to controls, CSX patients showed a lower heart/mediastinum (H/M) ratio of MIBG uptake (1.69 (0.24) vs 2.2 (0.3), p<0.001) and a higher cardiac MIBG defect score (25 (22) vs 4 (2), p = 0.002). Both CFR to adenosine (3.31 (1.1) vs 1.94 (0.6), p<0.001) and CFR to CPT (2.35 (0.5) vs 1.63 (0.4), p<0.001) were lower in CSX patients than in controls. In CSX patients, however, no correlation was found between MIBG H/M ratio and CFR to adenosine (r = 0.17; p = 0.38) and to CPT (r = -0.28; p = 0.13), as well as between MIBG uptake score in the LAD territory and CFR to adenosine (r = 0.14; p = 0.47) and to CPT (r = 0.06; p = 0.73). CONCLUSION: Our data show striking abnormalities in cardiac adrenergic nerve function and in coronary microvascular function in CSX patients. However, no significant relation between the two abnormalities was found. Further studies are needed to clarify the mechanisms and the role of MIBG defects in CSX patients.
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3-Yodobencilguanidina/farmacocinética , Fibras Adrenérgicas/metabolismo , Angina Microvascular/metabolismo , Miocardio/metabolismo , Radiofármacos/farmacocinética , Adenosina , Fibras Adrenérgicas/diagnóstico por imagen , Fibras Adrenérgicas/fisiología , Anciano , Estudios de Casos y Controles , Frío/efectos adversos , Circulación Coronaria/efectos de los fármacos , Electrocardiografía/efectos de los fármacos , Femenino , Corazón/diagnóstico por imagen , Humanos , Masculino , Microcirculación/efectos de los fármacos , Angina Microvascular/diagnóstico por imagen , Angina Microvascular/fisiopatología , Persona de Mediana Edad , Tomografía de Emisión de Positrones , VasodilatadoresAsunto(s)
Angina Microvascular , Trastornos de la Coagulación Sanguínea/complicaciones , Angiografía Coronaria , Ecocardiografía de Estrés , Electrocardiografía , Prueba de Esfuerzo , Reflujo Gastroesofágico/complicaciones , Humanos , Hiperinsulinismo/complicaciones , Metabolismo de los Lípidos , Imagen por Resonancia Magnética , Angina Microvascular/complicaciones , Angina Microvascular/diagnóstico , Angina Microvascular/diagnóstico por imagen , Angina Microvascular/etiología , Angina Microvascular/metabolismo , Pronóstico , Calidad de VidaRESUMEN
Adiponectin, an adipocyte-derived protein, has been shown to have vasculoprotective effects. This study examined the possible relationship between coronary vasomotor function and the transcardiac gradient of adiponectin, reflecting adiponectin utilization and/or accumulation in the coronary vascular bed. The epicardial diameter and blood flow response of the left anterior descending coronary artery to intracoronary infusions of ACh was analyzed in 108 consecutive subjects who had a normal coronary angiogram and left ventriculogram. Adiponectin levels were measured by ELISA in plasma obtained from the aortic root (Ao) and the anterior interventricular vein (AIV). Adiponectin levels in the AIV were lower than levels in the Ao. In multivariate linear regression analysis, the transcardiac gradient of adiponectin (Ao - AIV levels) showed a positive correlation with increases in epicardial coronary diameter and coronary blood flow in response to ACh that was independent of traditional coronary risk factors. The transcardiac gradient of adiponectin was not significantly associated with the coronary dilator response to isosorbide dinitrate and the coronary flow response to sodium nitroprusside. In other groups of patients with coronary spastic angina (n = 41) or microvascular angina (n = 32) who had impaired coronary vasomotor responses, there was no significant gradient of adiponectin between the Ao and AIV. The transcardiac gradient of adiponectin may modulate endothelial vasomotor function in large and resistance coronary arteries and may play a role in the pathogenesis of diseases presenting with coronary vasomotor dysfunction.
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Adiponectina/metabolismo , Vasos Coronarios/fisiología , Endotelio Vascular/fisiología , Resistencia Vascular/fisiología , Sistema Vasomotor/fisiología , Anciano , Angina de Pecho/etiología , Angina de Pecho/metabolismo , Angina de Pecho/fisiopatología , Estudios de Casos y Controles , Circulación Coronaria/fisiología , Vasos Coronarios/inervación , Vasos Coronarios/patología , Endotelio Vascular/inervación , Femenino , Humanos , Masculino , Angina Microvascular/etiología , Angina Microvascular/metabolismo , Angina Microvascular/fisiopatología , Persona de Mediana Edad , Miocardio/metabolismo , Flujo Sanguíneo Regional/fisiologíaRESUMEN
OBJECTIVES: This study sought to clarify the differences of intracellular and extracellular magnesium levels in patients with cardiac syndrome X. METHODS: We evaluated the intracellular and extracellular magnesium status of 22 patients with cardiac syndrome X (group A) and 22 age--and gender--matched disorder-free control subjects (group B). Levels of magnesium were determined in serum, urine, erythrocytes, and the 24-h magnesium retention rate was calculated by a magnesium loading test. RESULTS: Group A showed a higher 24-h magnesium retention rate (49.8 +/- 1.3% vs. 32.6 +/- 7.5%, p < 0.05) and a lower intracellular concentration of magnesium in erythrocytes than group B (3.7 +/- 1.4 vs. 5.6 +/- 1.3 fg/cell, p < 0.05), demonstrating the presence of magnesium deficiency in group A. There were no significant differences in the serum concentration of magnesium between groups A and B (0.87 +/- 0.23 vs. 0.83 +/- 0.15 mmol/l). CONCLUSIONS: This study demonstrated that the intracellular magnesium level decreased in patients with cardiac syndrome X.
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Eritrocitos/química , Magnesio/metabolismo , Angina Microvascular/metabolismo , Adulto , Femenino , Humanos , Magnesio/sangre , Magnesio/fisiología , Magnesio/orina , Masculino , Angina Microvascular/sangre , Angina Microvascular/orina , Persona de Mediana EdadRESUMEN
BACKGROUND: Syndrome X has been recognized as a disease that is primarily reflected in the cardiac microvasculature. Myocardial metabolism in this condition has been studied, but not in relation to small vessel pathology. METHODS AND RESULTS: In order to examine the relationship between myocardial metabolism and small vessel pathology, 24 consecutive patients with syndrome X (7 men, 17 women; mean age 58 years) were evaluated by the thallium exercise stress test, positron emission tomography using F-18 fluoro-deoxyglucose (FDG), and an endomyocardial biopsy. All patients showed either diffuse or focal increase in the myocardial uptake of FDG, but only 17 patients (71%) showed hypoperfused areas with partial or complete redistribution in the thallium study. Quantification of myocardial FDG uptake revealed that the value in syndrome X patients was 10-fold higher than in controls (p<0.0001). Histopathological examination revealed that in syndrome X there is an extensive increase in smooth muscle cells and thickening of the vascular wall, even in capillary vessels, and the small vessel lumen was markedly narrowed. There was a significant inverse correlation between FDG myocardial uptake and the microvessel luminal area. CONCLUSIONS: In syndrome X patients, myocardial FDG uptake is increased extensively, which is strongly associated with narrowed myocardial microvasculature.
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Glucosa/metabolismo , Angina Microvascular/metabolismo , Angina Microvascular/patología , Miocardio/metabolismo , Miocardio/patología , Adulto , Anciano , Angiografía Coronaria , Vasos Coronarios/metabolismo , Vasos Coronarios/patología , Prueba de Esfuerzo , Femenino , Fluorodesoxiglucosa F18/metabolismo , Humanos , Masculino , Angina Microvascular/terapia , Persona de Mediana Edad , Contracción Miocárdica/fisiología , Radiofármacos/metabolismo , Radioisótopos de Talio/metabolismo , Tomografía Computarizada de EmisiónRESUMEN
BACKGROUND: Obesity, hypertension, and non-insulin-dependent diabetes mellitus (NIDDM) are associated with microvascular rarefaction in the myocardium and this contributes to increase cardiovascular morbidity and mortality. At present, controversial data exist in medical literature regarding the specific role of angiotensin-converting enzyme (ACE) inhibitors concerning angiogenesis in different tissues. The present study was designed to determine the possible beneficial effects of an ACE inhibitor perindopril on myocardial angiogenesis in an animal model of obesity, hypertension, and NIDDM, such as the obese Zucker rat (OZR) and control lean Zucker rats (LZR). METHODS AND RESULTS: Ten-week-old male OZR (fa/fa) and LZR (Fa/fa) were used in this study: OZR group (G1, n = 10), OZR with perindopril group (G2, n = 10); LZR group (G3, n = 10). For 6 months, G2 received a daily dose of 3 mg/kg of perindopril, by gavage, and G1 and G3 received an equal volume of vehicle throughout the experiment. After 6 months of treatment, all rats were killed, hearts were harvested for pathology studies, including immunohistochemistry, using monoclonal antibodies against rat endothelial cell (RECA-1) and endothelial nitric oxide synthase. At the end of the study, OZR treated with perindopril presented: 1) lower blood pressure (BP) (127 +/- 3.2 v 152.4 +/- 3 mm Hg, P <.01) and 2) lower heart weight/100 g body weight (0.22 +/- 0.02 v 0.36 +/- 0.04 g, P <.01) than OZR untreated. Moreover, OZR that received perindopril showed higher: 1) myocyte density (2044 +/- 67 v 847 +/- 91 myocytes/mm(2), P <.01) and 2) capillary density (1348 +/- 118 v 436 +/- 78 capillaries/mm(2), P <.01); higher amount of: 1) vascular endothelial growth factor (VEGF) in the myocardium (P <.01) and higher percentage of capillaries with positive immunostaining for eNOS (P <.01), compared with untreated OZR. There was a correlation between both the amount of VEGF in myocardium and the number of capillaries (r = 0.88; P <.01) and VEGF and eNOS expression in myocardial capillaries (r = 0.93; P <.01) in OZR treated with perindopril. Finally, OZR that received P showed an improvement in insulin/glucose ratio (P <.01) when compared with untreated OZR. CONCLUSIONS: These results suggest that ACE inhibition by perindopril improves myocardial angiogenesis in this animal model of human metabolic syndrome. The pathway that involves bradykinin, eNOS, and VEGF could be involved in this effect; however, because no additional antihypertensive treatment group was included in our study, the BP-lowering effect cannot be excluded.
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Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Angina Microvascular/tratamiento farmacológico , Miocardio/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Perindopril/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Glucemia , Presión Sanguínea , Circulación Coronaria/efectos de los fármacos , Modelos Animales de Enfermedad , Inmunohistoquímica , Masculino , Angina Microvascular/metabolismo , Miocardio/patología , Neovascularización Patológica/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Tamaño de los Órganos , Perindopril/farmacología , Ratas , Ratas ZuckerRESUMEN
Cardiological syndrome X (CSX) is defined as effort anginal pain, positive exercise tolerance test and absence of angiographically documented stenosis in coronary arteries. Some genetic predispositions and metabolic disturbances can participate in development of this syndrome. The aim of our study was to investigate the associations between some biochemical parameters and polymorphism of ACE and eNOS (VNTR and Glu298Asp) genes in patients with CSX. 36 patients with CSX and a control group of 30 healthy volunteers were included in the study. The genotypes were determined by the polymerase chain reaction. Our study revealed that patients with CSX exerted lower fasting NOx levels, tended to have higher insulin values measured at 1 h of oral glucose tolerance test and higher levels of triglycerides and free fatty acids during oral lipid tolerance test. Patients with genotype T/T Glu298Asp of eNOS and 4/4 VNTR of eNOS revealed lower levels of NOx compared to patients with genotypes G/G and 5/5, respectively (30.5 +/- 7.2 vs 13.2 +/- 4.5; 28.6 +/- 8.4 vs 14.2 +/- 7.4; p<0.05). Thus, we conclude that disturbances in free fatty acid utilization, estimated by postprandial lipaemic test play important roles in the development of endothelial injury in CSX.
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Angina Microvascular/metabolismo , Óxido Nítrico Sintasa/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Adulto , Estudios de Casos y Controles , Ácidos Grasos no Esterificados/sangre , Femenino , Genotipo , Humanos , Insulina/sangre , Masculino , Angina Microvascular/sangre , Angina Microvascular/genética , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo III , Reacción en Cadena de la Polimerasa , Triglicéridos/sangreRESUMEN
This study assessed the changes in digoxin and some other metabolites of the isoprenoid pathway in metabolic syndrome X presenting with multiple lacunar state. The isoprenoid pathway and digoxin status was also studied for comparison in individuals of differing hemispheric dominance to find out the role of cerebral dominance in the genesis of syndrome X. There was an increase in plasma HMG CoA reductase activity with a consequent increase in serum digoxin, which caused a reduction in RBC membrane Na(+)-K+ ATPase activity. There was an increase in serum tryptophan and its metabolites and a decrease in tyrosine and its metabolites. Serum magnesium was decreased with consequent alteration in the metabolism of glycosaminoglycans and glycolipids. Increase in dolichol, another product of the isoprenoid pathway, resulted in alteration in glycoprotein metabolism. Changes in the composition of membrane glycosaminoglycans, glycoproteins and cholesterol: phospholipid ratio were also observed in this disorder leading to decreased lysosomal stability. Decrease in ubiquinone, another isoprenoid metabolite, resulted in alteration in the free radical generation. Membrane Na(+)-K+ ATPase inhibition due to digoxin, altered membrane structure, increased tryptophan catabolites and decreased tyrosine catabolites can lead to increased intracellular calcium and reduced intracellular magnesium which can account for the symptoms of syndrome X. The biochemical patterns including hyperdigoxinemia observed in syndrome X correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance is a predisposing factor for syndrome X with multiple lacunar state.