RESUMEN
During recent years, resting heart rate was not considered as a cardiovascular risk factor. However, new evidences have showed that resting heart rate is an important prognostic factor for sudden cardiac death and heart failure in the general population, and especially among patients with known cardiac disease. Interestingly, resting heart rate not only predicts cardiac mortality but also all-cause mortality. The most common pathophysiological explanation is related to the fact that increased heart rate increases myocardial oxygen consumption and in parallel reduces coronary blood flow (reduction in the diastolic duration).
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Muerte Súbita Cardíaca/etiología , Insuficiencia Cardíaca/etiología , Frecuencia Cardíaca , Benzazepinas/uso terapéutico , Causas de Muerte , Canales Catiónicos Regulados por Nucleótidos Cíclicos/efectos de los fármacos , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/prevención & control , Depresión Química , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/prevención & control , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Ivabradina , Ensayos Clínicos Controlados Aleatorios como Asunto , Valores de Referencia , Factores de RiesgoRESUMEN
BACKGROUND: Muscular counterpulsation (MCP) was developed for circulatory assistance by stimulation of peripheral skeletal muscles. We report on a clinical MCP study in patients with and without chronic heart failure (CHF). METHODS AND RESULTS: MCP treatment was applied (30 patients treated, 25 controls, all under optimal therapy) for 30 minutes during eight days by an ECG-triggered, battery-powered, portable pulse generator with skin electrodes inducing light contractions of calf and thigh muscles, sequentially stimulated at early diastole. Hemodynamic parameters (ECG, blood pressure and echocardiography) were measured one day before and one day after the treatment period in two groups: Group 1 (9 MCP, 11 no MCP) with ejection fraction (EF) above 40% and Group 2 (21 MCP, 14 no MCP) below 40%. In Group 2 (all patients suffering from CHF) mean EF increased by 21% (p<0.001) and stroke volume by 13% (p<0.001), while end systolic volume decreased by 23% (p<0.001). In Group 1, the increase in EF (6%) and stroke volume (8%) was also significant (p<0.05) but less pronounced than in Group 2. Physical exercise duration and walking distance increased in Group 2 by 56% and 72%, respectively. CONCLUSIONS: Noninvasive MCP treatment for eight days substantially improves cardiac function and physical performance in patients with CHF.
Asunto(s)
Contrapulsación/métodos , Insuficiencia Cardíaca/terapia , Músculo Esquelético/fisiología , Adulto , Electrocardiografía , Prueba de Esfuerzo , Femenino , Insuficiencia Cardíaca/fisiopatología , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Skeletal muscular counterpulsation (MCP) has been used as a new noninvasive technique for treatment of low cardiac output. The MCP method is based on ECG-triggered skeletal muscle stimulation. The purpose of the present study was to evaluate acute hemodynamic changes induced by MCP in the experimental animal. METHODS: Eight anaesthetized pigs (43+/-4 kg) were studied at rest and after IV â-blockade (10 mg propranolol) before and after MCP. Muscular counterpulsation was performed on both thighs using trains (75 ms duration) of multiple biphasic electrical impulses with a width of 1 ms and a frequency of 200 Hz at low (10 V) and high (30 V) amplitude. ECG-triggering was used to synchronize stimulation to a given time point. LV pressure-volume relations were determined using the conductance catheter. After baseline measurements, MCP was carried out for 10 minutes at low and high stimulation amplitude. The optimal time point for MCP was determined from LV pressure-volume loops using different stimulation time points during systole and diastole. Best results were observed during end-systole and, therefore, this time point was used for stimulation. RESULTS: Under control conditions, MCP was associated with a significant decrease in pulmonary vascular resistance (-18%), a decrease in systemic vascular resistance (-11%) and stroke work index (-4%), whereas cardiac index (+2%) and ejection fraction (+6%) increased slightly. Pressure-volume loops showed a leftward shift with a decrease in end-systolic volume. After â-blockade, cardiac function decreased (HR, MAP, EF, dP/dt max), but it improved with skeletal muscle stimulation (HR +10% and CI +17%, EF +5%). There was a significant decrease in pulmonary (-19%) and systemic vascular resistance (-29%). CONCLUSIONS: In the animal model, ECG-triggered skeletal muscular counterpulsation is associated with a significant improvement in cardiac function at baseline and after IV â-blockade. Thus, MCP represents a new, non-invasive technique which improves cardiac function by diastolic compression of the peripheral arteries and veins, with a decrease in systemic vascular resistance and increase in cardiac output.
Asunto(s)
Gasto Cardíaco Bajo/terapia , Contrapulsación , Corazón/fisiopatología , Animales , Presión Sanguínea , Gasto Cardíaco Bajo/fisiopatología , Estimulación Eléctrica , Electrocardiografía , Frecuencia Cardíaca , Músculo Esquelético , Volumen Sistólico , Sus scrofa , Resistencia VascularRESUMEN
BACKGROUND: Patency of small synthetic bypass grafts is inferior compared to autologous grafts for revascularization procedures. Titanium coating of foreign surfaces has shown to decrease thrombogenicity, enhance biocompatibility and promote adhesion of endothelial cells. The aim of this study was to test the effect of titanium coating of small diameter ePTFE grafts on short term patency, neo-endothelialization and neointimal proliferation. METHODS: Bilateral carotid graft interposition was performed in 5 pigs with uncoated (n=5) and titanium-coated (n=5) ePTFE grafts (internal diameter=4 mm, length=5 cm), thus each pig served as its own control. At the end of the study (30 +/- 3 days), patency and stenosis severity was assessed by carotid angiography. Animals were sacrificed and grafts were excised for histology and scanning electron microscopy. Morphometry of histologic sections was carried out to determine neointimal proliferation and percentage of neo-endothelial coverage. RESULTS: Patency rate was 80% for uncoated and titanium-coated grafts. Quantitative angiography did not show any significant difference in lumen size between two groups. Morphometry revealed a significantly higher cellular coverage with CD31 positive endothelial cells for titanium-coated (84 +/- 19%) than uncoated grafts (48 +/- 26%, p<0.001). There was a non significant trend (p=0.112) towards increased neointimal proliferation in titanium-coated (94 +/- 61 micron2/micron) compared to uncoated grafts (60 +/- 57 micron2/micron). CONCLUSIONS: Patency rate in uncoated and titanium-coated ePTFE grafts is similar at one month. However, titanium coated grafts show a significant improvement in neo-endothelialization compared to uncoated grafts.
Asunto(s)
Prótesis Vascular , Materiales Biocompatibles Revestidos , Oclusión de Injerto Vascular/prevención & control , Titanio , Animales , Implantación de Prótesis Vascular/instrumentación , Arterias Carótidas , Oclusión de Injerto Vascular/patología , Microscopía Electrónica de Rastreo , Politetrafluoroetileno , PorcinosRESUMEN
AIMS: Patency failure of small vascular synthetic grafts is still a major problem for coronary and peripheral revascularization. Thus, three new surface coatings of small synthetic grafts were tested in an acute pig model to evaluate their thrombogenicity (extracorporeal arterio-venous shunt) and in a chronic rat model to evaluate the tissue reaction they induced (subcutaneous implantation). METHODS: In five domestic pigs (25-30 kg) an extracorporeal femoro-femoral arterio-venous shunt model was used. The study protocol included first a non-heparinized perfusion sequence followed by graft perfusion after 10,000 UI iv heparin. Grafts were perfused for 3 and 9 minutes. The following coatings were tested on ePTFE grafts: poly-propylene sulphide (PPS)--poly-ethylene glycol (PEG) (wet and dry applications) as well as carbon. Two sets of control were used, one dry and one wet (vehicle only). After perfusion grafts were examined by scanning electron microscopy for semi-quantitative assessment (score 0-3) of cellular and microthrombi deposition. To assess tissue compatibility, pieces of each material were implanted subcutaneously in 16 Wistar rats. At 2, 4, 8, 12 weeks four animals each were sacrificed for semi-quantitative (score 0-3) histologic evaluation of tissue reaction. RESULTS: In the pig model, cellular deposition and microthrombi formation increased over time. In non- heparinized animals, the coatings did not improve the surface characteristics, since they did not prevent microthrombi formation and cellular deposition. In heparinized animals, thrombogenicity was lowest in coated grafts,especially in PPS -PEG dry (p<0.05), and highest in controls. Cell deposition was lowest in PPS-PEG dry, but this difference was not statistically significant vs.controls. In the rat model,no significant differences of the tissue reaction could be shown between materials. CONCLUSION: While all coatings failed to add any benefit for lowering tissue reaction, surface coating with PPS -PEG (dry application) reduced thrombogenicity significantly (in heparinized animals) and thus appears to be promising for improving graft patency of small synthetic vascular prostheses.
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Prótesis Vascular , Arteria Femoral/patología , Polietilenglicoles/química , Polipropilenos/química , Politetrafluoroetileno/química , Trombosis/patología , Trombosis/prevención & control , Animales , Materiales Biocompatibles Revestidos/química , Arteria Femoral/cirugía , Ensayo de Materiales , Ratas , Ratas Wistar , Porcinos , Resultado del TratamientoRESUMEN
Homocysteine (tHcy) is an intermediate sulfur-containing amino acid which acts as a methyl group donor for methionine metabolism. Increased serum concentrations (=hyperhomocysteinemia, >10 micromol/l) have been associated with an increased cardiovascular risk. Homocystinuria, an infrequent genetic disease usually due to lack of cystathione beta-synthase, has been found with severely elevated serum homocysteine values (>150 micromol/l). Functional gene polymorphisms of key enzymes (e.g., N5,N10-methylene-tetrahydrofolate reductase) and dietary B-vitamin deficiencies in the elderly are, however, frequent in the 'Western' population. Hyperhomocysteinemia has been associated with other vascular effects such as atherothrombosis and endothelial dysfunction due to its auto-oxidative potential, thereby increasing the production of reactive oxygen species. Other effects may involve neurodegenerative diseases such as Alzheimer or dementia praecox of the elderly. Therapeutic interventions lowering tHcy may therefore offer novel tools for the prevention and treatment of atherosclerosis. B-vitamin supplementation (folic acid=vitamin B9, vitamin B6 and vitamin B12) is an efficient and safe tHcy-lowering therapy, decreases tHcy by 30%-50% and has been shown to lower cardiovascular morbidity and mortality. Furthermore, folic acid supplementation has been shown to reduce or even almost eliminate neurotubular birth defects (spina bifida) and to markedly decrease the rate of megaloblastic anemia. Thus, fortification of flour with folic acid in the USA was advocated several years ago in order to prevent these entities.
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Homocisteína/fisiología , Hiperhomocisteinemia/tratamiento farmacológico , Complejo Vitamínico B/uso terapéutico , Animales , Aterosclerosis/etiología , Enfermedades Cardiovasculares/etiología , Homocisteína/sangre , Humanos , Hiperhomocisteinemia/complicaciones , Factores de Riesgo , Accidente Cerebrovascular/etiologíaRESUMEN
Erectile dysfunction is one of the major obstacles for noncompliance in the antihypertensive treatment. It has been shown that various antihypertensive drugs have a negative influence on sexual activity such as diuretics and beta-blockers. Thus, the purpose of the present study was to evaluate the effect of valsartan, an AT1-receptor antagonist, or its combination with hydrochlorothiazide on sexual activity in hypertensive patients. A total of 2202 patients (mean age 54+/-8 years) with hypertension systolic blood pressure (SBP)> or =140 mmHg, diastolic blood pressure (DBP)> or =95 mmHg), or with pretreated hypertension, were included in the present analysis. Blood pressure was measured at baseline, after 8 and 16 weeks, respectively. Sexual activity was assessed with a questionnaire at each of the three visits. Sexual activity (intercourse per week) was determined in three groups: controls (n=27; conventional therapy); valsartan group (n=1899); valsartan in combination with hydrochlorothiazide (n=276). There were 26 drop outs. SBP (-18.6 mmHg) and DBP (-11.6 mmHg) decreased significantly in all three groups. Sexual activity decreased slightly in controls from 1.3 to 0.9 times per week (NS), whereas it increased in the valsartan group from 1.0 to 1.6 times during follow-up (P<0.0001). Similarly, sexual activity increased in the combination group from 0.9 to 1.3 times per week during follow-up (P<0.0001). No sexual activity was reported by 467 (21%) of the 2202 patients at baseline and 154 (7%) at 16 weeks follow-up (P<0.05). Impaired sexual activity is common in hypertensive patients (app. 20%). Valsartan increases the rate of sexual intercourses per week, whereas conventional therapy affects sexual activity adversely.
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Antihipertensivos/administración & dosificación , Coito , Hidroclorotiazida/administración & dosificación , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Tetrazoles/administración & dosificación , Valina/análogos & derivados , Valina/administración & dosificación , Adulto , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Diuréticos , Quimioterapia Combinada , Humanos , Hidroclorotiazida/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Conducta Sexual/efectos de los fármacos , Inhibidores de los Simportadores del Cloruro de Sodio/administración & dosificación , Encuestas y Cuestionarios , Tetrazoles/efectos adversos , Valina/efectos adversos , ValsartánRESUMEN
AIMS: A simple management strategy is required for patients with acute pulmonary embolism which allows a rapid and reliable diagnosis in order to start timely and appropriate treatment. METHODS AND RESULTS: Two hundred and four consecutive patients with suspected pulmonary embolism were managed according to a standardized protocol based on the clinical pretest probability and the initial haemodynamic presentation (shock index=heart rate divided by systolic blood pressure). Patients with a high pretest probability and a positive shock index (> or =1) (n=21) underwent urgent transthoracic echocardiography. Based on the presence or absence of right ventricular dysfunction, reperfusion treatment was initiated immediately. Patients with a negative shock index (<1) (n=183) underwent diagnostic evaluation including pretest probability, D-dimer, and spiral computed tomography (CT) as first-line tests. Echocardiography was performed only when a central pulmonary embolism was found in the spiral CT(n=33). According to our strategy, 98 patients met the diagnostic criteria of pulmonary embolism: 75 patients (all shock index <1) were treated with heparin alone, 16 (seven had a shock index > or =1) with thrombolysis, four (all shock index > or =1) with catheter fragmentation, and three (all shock index > or =1) with surgical embolectomy. The all-cause mortality rate at 30 days was 5%, and at 6 months 11%. Right ventricular dysfunction on baseline echocardiography was not associated with a higher mortality rate at 6 months (logrank 2.4, P=0.12). CONCLUSIONS: The novel management strategy for patients with suspected pulmonary embolism resulted in a rapid diagnosis and treatment with a low 30-day mortality. In patients with pulmonary embolism and a positive shock index, time-consuming imaging tests can be avoided to reduce the risk of sudden death and not to delay reperfusion therapy.
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Embolia Pulmonar/terapia , Enfermedad Aguda , Administración Oral , Anciano , Anticoagulantes/administración & dosificación , Ecocardiografía , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Masculino , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico , Reperfusión/métodos , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/terapia , Análisis de Supervivencia , Tomografía Computarizada Espiral/métodos , Filtros de Vena CavaRESUMEN
AIMS: Restenosis after percutaneous coronary angioplasty remains an important limitation of this procedure. This study evaluates whether elevated total plasma homocysteine levels contribute to the development of restenosis after coronary angioplasty. METHODS AND RESULTS: Two hundred and five patients were recruited after successful angioplasty of at least one coronary stenosis (> or =50%). End-points were restenosis (> or =50%) and a composite of major adverse cardiac events. Of the 205 patients, 183 (89.3%) underwent 6 months angiographic follow-up. Patients with restenosis had significantly higher homocysteine levels than those without (10.9+/- 3.9 micromol x l(-1) vs 9.3+/-3.8 micromol x l(-1), P<0.01). Homocysteine levels were significantly correlated to follow-up diameter stenosis (r=0.24, P=0.0001), especially in small vessels (<3 mm) treated with balloon angioplasty only (r=0.40, P<0.0005). Late lumen loss at follow-up was significantly smaller with homocysteine levels below 9 micromol x l(-1) (0.62+/-0.82 mm vs 0.90+/-0.77 mm, P<0.01). Restenosis rate (25.3% vs 50.0%, P<0.001) and major adverse cardiac events (15.7% vs 28.4%, P<0.05) were also significantly lower in patients with homocysteine levels below 9 micromol x l(-1). Multivariate analysis did not weaken these findings. CONCLUSION: Total plasma homocysteine is a strong predictor of restenosis and major adverse cardiac events after coronary angioplasty. Thus, plasma homocysteine appears to be an important cardiovascular risk factor influencing outcome after successful coronary angioplasty.
Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Reestenosis Coronaria/sangre , Reestenosis Coronaria/etiología , Homocisteína/sangre , Anciano , Biomarcadores/sangre , Angiografía Coronaria , Reestenosis Coronaria/mortalidad , Estenosis Coronaria/complicaciones , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/terapia , Vasos Coronarios/cirugía , Determinación de Punto Final , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Estudios Prospectivos , Recurrencia , Índice de Severidad de la Enfermedad , Estadística como Asunto , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Diuréticos/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Antagonistas Adrenérgicos beta/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Diuréticos/efectos adversos , Quimioterapia Combinada , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/mortalidad , Humanos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Beta-adrenergic blocking agents are the cornerstone in the treatment of coronary artery disease (CAD). The exact pathophysiologic mechanism is not clear but depends largely on the oxygen-sparing effect of the drug. Thus, the effect of metoprolol on coronary flow reserve and coronary flow velocity reserve (CFVR) was determined in patients with CAD. METHODS: Coronary blood flow velocity was measured with the Doppler flow wire in 23 patients (age: 56 +/- 10) undergoing percutaneous transluminal coronary angioplasty for therapeutic reasons. Measurements were carried out at rest, after 1-min vessel occlusion (postischemic CFVR) as well as after intracoronary adenosine (pharmacologic CFVR) before and after 5 mg intravenous metoprolol. In a subgroup (n = 15), absolute flow was measured from coronary flow velocity multiplied by coronary cross-sectional area. RESULTS: Rate-pressure product decreased after metoprolol from 9.1 to 8.0 x 10(3) mm Hg/min (p < 0.001). Pharmacologic CFVR was 2.1 at rest and increased after metoprolol to 2.7 (p = 0.002). Likewise, postischemic CFVR increased from 2.6 to 3.3 (p < 0.001). Postischemic CFVR was significantly higher than pharmacologic CFVR before as well as after metoprolol. Coronary vascular resistance decreased after metoprolol from 3.4 +/- 2.0 to 2.3 +/- 0.7 mm Hg x s/cm (p < 0.02). CONCLUSIONS: The following conclusions were drawn from this study. Metoprolol is associated with a significant increase in postischemic and pharmacologic CFVR. However, postischemic CFVR is significantly higher than pharmacologic CFVR. The increase in CFVR by metoprolol can be explained by a reduction in vascular resistance. The increase in CFVR (= increased supply) and the reduction in oxygen consumption (= decreased demand) after metoprolol explain the beneficial effect of this beta-blocker in patients with CAD.
Asunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Circulación Coronaria/efectos de los fármacos , Ecocardiografía Doppler/efectos de los fármacos , Metoprolol/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Anciano , Angioplastia Coronaria con Balón , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Consumo de Oxígeno/efectos de los fármacos , Resistencia Vascular/efectos de los fármacosRESUMEN
BACKGROUND: Coronary stents prevent constrictive arterial remodeling but stimulate neointimal hyperplasia. Stainless steel induces a metallic foreign body reaction, which is absent for titanium. The hypothesis of the present study was that titanium renders the stent surface biologically inert, with reduced platelet and fibrinogen binding. METHODS AND RESULTS: Twelve pigs were instrumented with a stainless steel and 2 titanium-nitride-oxide-coated stents (TiNOX 1, ceramic; TiNOX 2, metallic). Animals were restudied after 6 weeks. Histological specimens of stented segments were analyzed by digital morphometry. Platelet adhesion and fibrinogen binding studies were performed in the perfusion chamber. Under in vitro conditions, TiNOX 1 showed reduced platelet adhesion (65+/-3%) compared with TiNOX 2 (72+/-5%; P<0.05) and stainless steel (71+/-4%; P<0.05). Platelet adhesion 48 hours after incubation with human plasma, however, was not different between TiNOX 1 (17+/-3%) and 2 (15+/-3%) but was significantly higher with stainless steel (23+/-2%; P<0.05). Fibrinogen binding was significantly reduced with TiNOX 2 (54+/-3%) compared with TiNOX 1 (82+/-4%, P<0.05) or stainless steel (100%, P<0.05). Histomorphometry revealed a significantly larger neointimal area in stainless steel (2.61+/-1.12 mm(2)) than in TiNOX 1-coated (1.47+/-0.84 mm(2), P<0.02) or TiNOX 2-coated (1.39+/-0.93 mm(2), P<0.02) stents. The reductions were 44% and 47%, respectively. CONCLUSIONS: TiNOX coating significantly reduces neointimal hyperplasia in stainless steel stents. The antiproliferative effect was similar for both TiNOX coatings, suggesting that the electrochemical properties are more important for attenuation of neointimal proliferation than the observed differences in platelet adhesion and fibrinogen binding.
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Materiales Biocompatibles Revestidos/farmacología , Hiperplasia/prevención & control , Stents/normas , Titanio/farmacología , Túnica Íntima/efectos de los fármacos , Aleaciones/química , Aleaciones/metabolismo , Aleaciones/farmacología , Animales , Implantación de Prótesis Vascular , División Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/metabolismo , Vasos Coronarios/patología , Vasos Coronarios/cirugía , Femenino , Fibrinógeno/metabolismo , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/patología , Oclusión de Injerto Vascular/prevención & control , Hiperplasia/etiología , Hiperplasia/patología , Técnicas In Vitro , Masculino , Adhesividad Plaquetaria/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Stents/efectos adversos , Propiedades de Superficie/efectos de los fármacos , Porcinos , Titanio/química , Titanio/metabolismo , Túnica Íntima/patologíaRESUMEN
BACKGROUND: A family of aspartate-specific cysteinyl proteases, named caspases, mediates programmed cell death, apoptosis. In this function, caspases are important for physiological processes such as development and maintenance of organ homeostasis. Caspases are, however, also engaged in aging and disease development. The factors inducing age-related caspase activation are not known. Xanthurenic acid, a product of tryptophan degradation, is present in blood and urine, and accumulates in organs with aging. RESULTS: Here, we report triggering of apoptotic key events by xanthurenic acid in vascular smooth muscle and retinal pigment epithelium cells. Upon exposure of these cells to xanthurenic acid a degradation of ICAD/DFF45, poly(ADP-ribose) polymerase, and gelsolin was observed, giving a pattern of protein cleavage characteristic for caspase-3 activity. Active caspase-3, -8 and caspase-9 were detected by Western blot analysis and immunofluorescence. In the presence of xanthurenic acid the amino-terminal fragment of gelsolin bound to the cytoskeleton, but did not lead to the usually observed cytoskeleton breakdown. Xanthurenic acid also caused mitochondrial migration, cytochrome C release, and destruction of mitochondria and nuclei. CONCLUSIONS: These results indicate that xanthurenic acid is a previously not recognized endogenous cell death factor. Its accumulation in cells may lead to accelerated caspase activation related to aging and disease development.
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Apoptosis , Caspasas/metabolismo , Xanturenatos/toxicidad , Caspasa 3 , Citoesqueleto/efectos de los fármacos , Citoesqueleto/ultraestructura , Activación Enzimática , Humanos , Persona de Mediana Edad , Mitocondrias/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/enzimología , Músculo Liso Vascular/ultraestructura , Triptófano/metabolismo , Xanturenatos/metabolismoRESUMEN
OBJECTIVES: The goals of this study were to determine regional systolic function of the septum and to relate it to regional wall thickness and wall stress. BACKGROUND: Wall thickening, a parameter of systolic function, is determined by wall thickness and wall stress. In patients with hypertrophic obstructive cardiomyopathy (HOCM), hypertrophic nonobstructive cardiomyopathy (HNCM), and hypertensive heart disease (HHD), regional systolic function of normal and hypertrophic septal regions has been incompletely characterized by 2-dimensional echocardiography. Thus, multiplane transesophageal echocardiography with 3-dimensional reconstruction of the septum was used. METHODS AND RESULTS: In 49 patients (15 controls, 11 with HOCM, 8 with HNCM, and 15 with HHD) 4 parallel (2 basal and 2 apical) equidistant short-axis cross sections from base to apex were obtained from the reconstructed septum. In each short-axis cross section, 6 wall-thickness measurements were made in 15 degrees intervals at end diastole and end systole, for a total of 48 measurements in each patient. Fractional thickening was calculated as wall thickening divided by end-diastolic wall thickness. Wall thickness of the basal cross sections was significantly thicker (P < .001) in HOCM and HNCM than in HHD. However, circumferential wall thickness was more evenly distributed in HNCM and HHD when compared with HOCM. In the basal cross sections, fractional thickening was similarly reduced in all hearts, though basal wall stress was significantly different in all groups (P < .001). In the apical cross sections, wall thickness was similar in all diseased hearts, but fractional thickening was better (P < .001) and wall stress lower (P < .001) in HNCM than in HOCM and HHD. CONCLUSIONS: In septal regions without or with only mild hypertrophy, regional systolic function is preserved and appears to be determined by hemodynamic factors such as wall stress. However, in regions with moderate to severe hypertrophy, systolic function is markedly and uniformly impaired in all groups, which seems not to be caused by differences in wall thickness and wall stress but by the degree of the myocardial disease process.
Asunto(s)
Cardiomiopatía Hipertrófica/diagnóstico , Ecocardiografía Tridimensional , Ecocardiografía , Ecocardiografía Transesofágica , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVE: Immunosuppressive agents have been proposed to reduce neointimal hyperplasia in synthetic vascular grafts. Thus, the purpose of the present study was to evaluate the safety and efficacy of rapamycins (systemic vs. local vs. oral administration) and mycophenolate mofetil (MMF) to reduce intimal hyperplasia in infrarenal synthetic vascular grafts of the rat. METHODS: Fifty-four Wistar rats (250 g) completed the study after a synthetic vascular graft (ePTFE, Gore-tex, 2 mm diameter, 10 mm length) was implanted end-to-end in the infrarenal aorta. The animals were divided into three groups: group 1 consisted of 12 control animals, group 2 consisted of 37 rats receiving rapamycins, either per os (RAD, 1.5 or 3 mg/kg), intraperitoneally (RPM, 1.5 or 3 mg/kg) or locally (RPM soaking of the graft); and in group 3 (n=5), MMF (40 mg/kg) was administered orally. The animals were followed weekly with weight controls and signs of toxicity for 30 (n=37) and 60 (n=17) days, respectively. All animals were sacrificed and underwent histological examination at completion of the study. RESULTS: All animals survived in groups 1 and 3, but five died in group 2. The weight gain was normal in all groups, except for the subgroup 2a receiving high dose rapamycins orally. All rats in group 3 suffered from diarrhea, whereas animals receiving high dose rapamycins showed toxic signs (hair loss, wound healing problems). Histological examination showed a significant increase in intimal hyperplasia in group 1 (0.03+/-0.01 and 0.14+/-0.05 microm after 30 and 60 days, respectively; P<0.01). Rapamycins in either application or dosage had no significant effect on intimal hyperplasia. CONCLUSIONS: Local or systemic administration of rapamycins has no effect on intimal hyperplasia in synthetic vascular grafts. In contrast, toxic signs with weight loss were observed in animals treated with high dose rapamycins, but not in those treated with MMF. Thus, in the rat model, immunosuppression with rapamycins or MMF cannot be recommended for the prevention of intimal hyperplasia in the synthetic vascular graft model.
Asunto(s)
Prótesis Vascular , Inmunosupresores/farmacología , Ácido Micofenólico/farmacología , Sirolimus/farmacología , Túnica Íntima/patología , Anastomosis Quirúrgica , Animales , Hiperplasia , Modelos Animales , Ácido Micofenólico/análogos & derivados , Politetrafluoroetileno , Ratas , Ratas Wistar , Grado de Desobstrucción VascularRESUMEN
BACKGROUND: We have previously demonstrated an association between elevated total plasma homocysteine levels and restenosis after percutaneous coronary angioplasty. We designed this study to evaluate the effect of lowering plasma homocysteine levels on restenosis after coronary angioplasty. METHODS: A combination of folic acid (1 mg), vitamin B12 (400 microg), and pyridoxine (10 mg)--referred to as folate treatment--or placebo was administered to 205 patients (mean [+/-SD] age, 61+/-11 years) for six months after successful coronary angioplasty in a prospective, double-blind, randomized trial. The primary end point was restenosis within six months as assessed by quantitative coronary angiography. The secondary end point was a composite of major adverse cardiac events. RESULTS: Base-tine characteristics and initial angiographic results after coronary angioplasty were similar in the two study groups. Folate treatment significantly lowered plasma homocysteine levels from 11.1+/-4.3 to 7.2+/-2.4 micromol per liter (P<0.001). At follow-up, the minimal luminal diameter was significantly larger in the group assigned to folate treatment (1.72+/-0.76 vs. 1.45+/-0.88 mm, P=0.02), and the degree of stenosis was less severe (39.9+/-20.3 vs. 48.2+/-28.3 percent, P=0.01). The rate of restenosis was significantly lower in patients assigned to folate treatment (19.6 vs. 37.6 percent, P=0.01), as was the need for revascularization of the target lesion (10.8 vs. 22.3 percent, P=0.047). CONCLUSIONS: Treatment with a combination of folic acid, vitamin B12, and pyridoxine significantly reduces homocysteine levels and decreases the rate of restenosis and the need for revascularization of the target lesion after coronary angioplasty. This inexpensive treatment, which has minimal side effects, should be considered as adjunctive therapy for patients undergoing coronary angioplasty.
Asunto(s)
Angioplastia Coronaria con Balón , Reestenosis Coronaria/prevención & control , Estenosis Coronaria/terapia , Ácido Fólico/uso terapéutico , Hiperhomocisteinemia/tratamiento farmacológico , Piridoxina/uso terapéutico , Vitamina B 12/uso terapéutico , Angiografía Coronaria , Estenosis Coronaria/complicaciones , Estenosis Coronaria/patología , Vasos Coronarios/patología , Supervivencia sin Enfermedad , Método Doble Ciego , Quimioterapia Combinada , Femenino , Homocisteína/sangre , Humanos , Hiperhomocisteinemia/complicaciones , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios ProspectivosRESUMEN
Mechanical compression of coronary artery stents may be associated with a fatal outcome as the result of refractory myocardial ischemia. We present the history of an 83-yr-old patient, who died owing to hemorrhagic shock 3 days after stent implantation, despite immediate cardiopulmonary resuscitation (CPR). Postmortem examination showed stent compression, probably due to mechanical deformation during CPR. This complication has been reported in two other cases in the literature, suggesting that CPR may be hazardous to patients with coronary artery stents.
Asunto(s)
Reanimación Cardiopulmonar/efectos adversos , Enfermedad Coronaria/terapia , Stents , Anciano , Anciano de 80 o más Años , Angiografía Coronaria , Resultado Fatal , Humanos , MasculinoRESUMEN
UNLABELLED: Mitral balloon valvuloplasty is the treatment of choice for severe mitral stenosis in young patients with a minimally calcified and pliable mitral valve. The present study reports the results of the first 65 patients undergoing mitral valvuloplasty in Zurich with the double-balloon or Inoue-balloon technique. Early outcome and late follow-up over 4.1 +/- 2.5 years were evaluated in these patients. PATIENTS: Percutaneous mitral valvuloplasty was performed in 65 patients (48 females and 12 males, mean age 41 +/- 11 years). The double-balloon technique was used in 25 and the Inoue-balloon technique in 40 patients. Left ventricular pressure as well as pressure gradient and valve area were calculated before and after the intervention. Mitral valvuloplasty was considered to be successful when the valve area was > or = 1.5 cm2 and the pressure gradient < or = 8 mm Hg. RESULTS: Mitral valvuloplasty was successful in 22 patients of group 1 and 39 patients of group 2. Acute complications were observed in 4 patients (6%), i.e. 1 perforation of the left atrium, 1 perforation of the left ventricle, 1 peripheral embolisation and 1 rupture of the mitral leaflet. Mitral valve area increased from 1.0 to 1.9 cm2 with the double-balloon and from 1.0 to 2.0 cm2 with the Inoue-balloon technique. The pressure gradient over the mitral valve dropped significantly from 11 to 4 mm Hg in group 1 and from 15 to 5 mm Hg in group 2. Left ventricular ejection fraction remained unchanged but left atrial pressure decreased significantly in the first group from 20 to 9 mm Hg and in the second group from 22 to 12 mm Hg. Long-term follow-up over 4.1 years showed a mild (not significant) decrease in valve area from 1.7 to 1.6 cm2 in both groups, with NYHA class unchanged and bicycle exercise capacity increased from 76 to 82%. CONCLUSIONS: Mitral valvuloplasty with either the double-balloon or Inoue-balloon technique provides excellent clinical, echocardiographic and haemodynamic results. The long-term follow-up demonstrated a mild decrease in mitral valve area but clinical symptomatology and physical exercise capacity remained unchanged. From a technical standpoint the Inoue-balloon technique is easier to use and has a lower complication rate (2.5%) compared to the double-balloon technique (12%). Thus, in the last few years the double-balloon technique has been replaced by the Inoue-balloon technique, with a good long-term outcome over the first 4-5 years of follow-up.