Eplerenone enhances cardioprotective effects of standard heart failure therapy through matricellular proteins in hypertensive heart failure.

AIMS: The addition of an aldosterone receptor antagonist on top of current optimal therapy (based on angiotensin II inhibition) has demonstrated an important clinical benefit in heart failure patients with systolic dysfunction. Whether this finding also applies to heart failure patients with preserved systolic function is unknown. Therefore, we have studied the effect of adding eplerenone to standard pharmacological heart failure therapy (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and diuretic and ß-blocker) in the progression of heart failure in spontaneously hypertensive heart failure (SHHF) rats. METHODS AND RESULTS: Two-month-old SHHF rats were randomized to receive no treatment (SHHF group), a standard heart failure therapy (quinapril-torasemide-carvedilol; ST-SHHF group), or the combination of eplerenone and standard heart failure therapy (Eple+ST-SHHF group) for 20 months. Untreated SHHF was characterized by progressive left ventricular hypertrophy, fibrosis, and myocardial contractile and relaxation abnormalities, leading to pulmonary congestion. Despite similar blood pressure control, the addition of eplerenone to standard heart failure therapy further prevented left ventricular hypertrophy, contractile and relaxation alterations, and pulmonary congestion than standard heart failure therapy alone. ST-SHHF and Eple + ST-SHHF rats showed similar inhibition of structural extracellular matrix proteins collagen I, collagen III and fibronectin and metalloproteinase (MMP)-2, MMP-7, MMP-12, and MMP-13. However, only the coadministration of eplerenone with standard heart failure therapy normalized the expression of matricellular proteins thrombospondin 1, tenascin C, periostin, and secreted protein acidic rich in cysteine/osteonectin to values comparable to normotensive rats. CONCLUSION: In a hypertensive heart failure rat model, the addition of eplerenone to conventional heart failure therapy further improves cardiac structural and functional parameters, delaying the progression of heart failure. These beneficial effects of eplerenone were associated with normalization of matricellular protein expression.

Skeletal myoblast implants induce minor propagation delays, but do not promote arrhythmias in the normal swine heart.

AIMS: Whether skeletal myoblast (SM) implants are proarrhythmic is still controversial due to conflicting pre-clinical and clinical data. We hypothesized that if SM implants are arrhythmogenic, they will facilitate the induction of ventricular tachyarrhythmias by promoting heterogeneous propagation of activation wavefronts. METHODS: Skeletal myoblast cells were harvested from 10 pigs. A month later, 125 ± 37 × 10(6) cells were subepicardially injected in an area of ∼2 cm(2) at the anterolateral aspect of the left ventricle. Four weeks later, a ventricular stimulation protocol was conducted. Once explanted, epicardial wavefronts over SM and adjacent control areas were optically mapped. Eight saline-injected animals were used as controls. To compare with clear arrhythmogenic substrates, propagation patterns were also evaluated in infarcted hearts and on a SM-implanted heart following amiodarone infusion. RESULTS: In SM hearts, fibrosis and differentiated SM cells were consistently found and no tachyarrhythmias were induced. Wavefronts propagated homogeneously over SM and adjacent areas, with no late activation zones, as opposed to the infarcted hearts. The time required for the wavefronts to depolarize both areas were similar, becoming only slightly longer at SM areas after an extra-stimulus (P = 0.025). Conduction velocities and APD(90) were also similar. Saline hearts showed similar results. The extent of the conduction delay was not related to the number of injected SM cells. CONCLUSION: In normal swine hearts, myoblast implants promote localized fibrosis and slightly retard epicardial wavefront propagation only after extra-stimuli. However, SM implants are not associated with local re-entry and do not facilitate ventricular tachyarrhythmias in the whole normal heart.

Rosuvastatin added to standard heart failure therapy improves cardiac remodelling in heart failure rats with preserved ejection fraction.

AIMS: Although statins may provide potential therapeutic pathways for patients with heart failure with preserved ejection fraction (HFpEF), no studies have evaluated statins in combination with standard HF therapy, which would reflect clinical practice more closely. To address this question, we evaluated whether rosuvastatin added to a standard HF therapy provides additional improvement in cardiac structure and function in rats with hypertensive heart failure (SHHF). METHODS AND RESULTS: Two-month-old SHHF rats were randomly assigned to four groups: (i) non-treated SHHF rats; (ii) rosuvastatin-treated SHHF rats; (iii) SHHF rats treated with quinapril plus torasemide plus carvedilol (considered as standard HF therapy); and (iv) SHHF rats treated with the combination of standard HF therapy and rosuvastatin. The administration of a standard anti-hypertensive HF therapy to SHHF rats for 17 months attenuated left ventricular (LV) chamber dilatation, cardiac hypertrophy, fibrosis, and inflammation compared with non-treated SHHF rats. Rosuvastatin alone prevented LV dilatation and cardiac inflammation similar to standard HF therapy-treated SHHF, despite being unable to normalize blood pressure (BP) or influence cardiac hypertrophy. However, and importantly, the addition of rosuvastatin to the standard HF therapy further prevented LV dilatation, preserved cardiac function, and normalized inflammation. CONCLUSION: These data show that the use of rosuvastatin plus a standard HF therapy results in a significant additional improvement in HF and cardiac remodelling in a rat model of HFpEF. These beneficial effects were independent of BP and plasma lipid changes, and seem to be due, at least in part, to decreased myocardial inflammation.

The role of postmortem study in the diagnosis of the cause of death in a young man: a rare case of Ehlers-Danlos syndrome type IV.

Diagnosis of the cause of death in young people is a challenge to both the clinician and the pathologist. Ehlers-Danlos syndrome (EDS) type IV is an inherited connective tissue disorder. It is characterised by thin translucent skin, abnormal fragility of blood vessels, and a typical facial appearance. The cause of death is usually due to large arterial rupture. We describe an unusual case of a 23-year-old man clinically diagnosed with myocarditis, who suffered from recurrent pulmonary haemorrhage and died of massive myocardial haemorrhage and ischaemia without coronary artery disease. Diagnosis of EDS type IV was made by autopsy. To our knowledge, this is the first such report in the literature. Delay in diagnosing this syndrome is common even when clinical features are typical, and the condition often goes unrecognised until necropsy. The diagnosis of EDS should be considered in young people who seek medical attention because of arterial rupture.

Assessment of microcirculatory remodeling with intracoronary flow velocity and pressure measurements: validation with endomyocardial sampling in cardiac allografts.

BACKGROUND: Intracoronary physiology techniques have been validated extensively for the assessment of epicardial stenoses but not for the lone study of coronary microcirculation. We performed a comparison between 4 intracoronary physiological indices with the actual structural microcirculatory changes documented in transplanted hearts. METHODS AND RESULTS: In 17 cardiac allograft patients without coronary stenoses, ECG, intracoronary Doppler flow velocity, and aortic pressure were digitally recorded before and during maximal hyperemia with a dedicated system. Postprocessing of data yielded 4 indices of microcirculatory status: coronary flow velocity reserve (2.13+/-0.59), instantaneous hyperemic diastolic velocity pressure slope (2.33+/-1.25 cm x s x (-1)mm Hg(-1)), coronary resistance index (1.65+/-0.88 mm Hg x cm(-1) x s(-1)), and coronary resistance reserve (2.36+/-0.65). Quantitative morphometry was performed in endomyocardial biopsies during the same hospital intake; arteriolar obliteration (76.57+/-6.95%) and density (2.00+/-1.22 arterioles per 1 mm(2)) and capillary density (645+/-179 capillaries per 1 mm(2)) were measured. Univariate regression analysis between intracoronary measurements and histological findings revealed that instantaneous hyperemic diastolic velocity-pressure slope correlated with arteriolar obliteration (r=0.58, P=0.014) and capillary density (r=0.60, P=0.012). Statistical adjustment revealed an independent contribution of arteriolar obliteration (beta=0.61, P=0.0009) and capillary density (beta=-0.60, P=0.0008) to instantaneous hyperemic diastolic velocity-pressure slope values, resulting in an excellent predictive model (r=0.84, P=0.0002). Coronary resistance index correlated only with capillary density (r=0.70, P=0.019). Relative indices (coronary flow velocity reserve and coronary resistance reserve) did not correlate significantly with arteriolar obliteration, capillary density, or arteriolar density. CONCLUSIONS: Intracoronary indices derived from pressure and flow, particularly instantaneous hyperemic diastolic velocity-pressure slope, appear to be superior to coronary flow velocity reserve in detecting structural microcirculatory changes. Both arteriolar obliteration and capillary rarefaction seem to influence microcirculatory hemodynamics independently.

[Thrombosis of an apparently normal thoracic aorta and arterial embolism]. / Trombosis en aorta torácica aparentemente normal y embolias arteriales.

With the advent of new imaging techniques, the aorta has been increasingly identified as a source of arterial embolism. The majority of thrombi occur in aneurysms or are adherent to atherosclerotic lesions in the abdominal aorta. Thrombi in the thoracic aorta are much less common, particularly in apparently normal aortas. Consequently, the natural history and optimal treatment of these lesions are not well-defined. The aim of this article was to describe the clinical characteristics, treatment, and outcome in three patients with thoracic aorta thrombosis and arterial embolism. Currently available literature on this pathology is reviewed and the differential diagnosis of these lesions is discussed.

Trombosis en aorta torácica aparentemente normal y embolias arteriales / Thrombosis of an apparently normal thoracic aorta and arterial embolism

Las nuevas técnicas de imagen han permitido identificar, en la aorta el origen de embolias arteriales. La mayoría de estos trombos se localizan en aneurismas o están adheridos a lesiones arterioscleróticas de aorta abdominal. Los trombos en aorta torácica son mucho menos frecuentes, especialmente en aortas aparentemente normales. En consecuencia, la historia natural y el tratamiento óptimo de estas lesiones no están bien definidos. El objetivo de este artículo es describir las características clínicas, el tratamiento y la evolución de 3 pacientes con trombosis de la aorta torácica y embolias arteriales. Se revisa la literatura disponible en relación con esta afección y se aborda el diagnóstico diferencial de estas lesiones (AU)

With the advent of new imaging techniques, the aorta has been increasingly identified as a source of arterial embolism. The majority of thrombi occur in aneurysms or are adherent to atherosclerotic lesions in the abdominal aorta. Thrombi in the thoracic aorta are much less common, particularly in apparently normal aortas. Consequently, the natural history and optimal treatment of these lesions are not well-defined. The aim of this article was to describe the clinical characteristics, treatment, and outcome in three patients with thoracic aorta thrombosis and arterial embolism. Currently available literature on this pathology is reviewed and the differential diagnosis of these lesions is discussed (AU)

Papel del factor de crecimiento de tejido conectivo en el daño vascular asociado a hipertensión en ratas. Interacción con la aldosterona / Role of connective tissue growth factor in vascular damage associated with hypertension in rats. Interaction with aldosterone

Introducción. El factor de crecimiento de tejido conectivo (CTGF) está implicado en diversas enfermedades, como la aterosclerosis, la fibrosis de la piel y diversas nefritis experimentales y humanas. Sin embargo, el papel de este factor profibrótico en el daño vascular asociado a hipertensión no se conoce completamente. Objetivo. Estudiar el posible papel del CTGF en el daño vascular asociado a hipertensión en ratas, así como la posible interacción con la aldosterona. Método. Se utilizaron ratas macho espontáneamente hipertensas (SHR) tratadas durante 10 semanas con 2 dosis de eplerenona, un antagonista selectivo de los receptores de mineralocorticoides (30 y 100 mg/kg/día), y ratas normotensas (WKY) como grupo control. Al final del tratamiento se midió la presión arterial sistólica (PAS) y la reactividad vascular en anillos de aorta. Se determinó la expresión vascular y los valores de proteína del CTGF, así como la morfometría de la aorta. Se estudió también el efecto directo de la aldosterona en células de músculo liso vascular (CMLV). Resultados. Las SHR presentaron unos valores de PAS mayores que las ratas controles WKY. Sólo el tratamiento con la dosis alta de eplerenona redujo significativamente estos valores. La expresión vascular génica y los valores de proteínas del CTGF aumentaron significativamente en las SHR respecto a las WKY. El tratamiento con ambas dosis de eplerenona disminuyó significativamente estos parámetros. La relajación dependiente del endotelio fue menor en SHR que en WKY, y el tratamiento con eplerenona normalizó esta respuesta. Las áreas del vaso, la luz y la media aumentaron significativamente en las SHR respecto a las WKY, así como la relación media/luz. El tratamiento con eplerenona redujo todas las áreas estudiadas y normalizó la relación media/luz. La incubación de CMLV con aldosterona aumentó la expresión de CTGF de forma dependiente de la dosis. Conclusiones. La aldosterona participa en las alteraciones tanto funcionales como estructurales asociadas a la hipertensión arterial. El CTGF es uno de los factores implicados en el proceso fibrótico vascular asociado a hipertensión arterial (AU)

Introduction. Connective tissue growth factor (CTGF) is associated with distinct diseases, including atherosclerosis, skin fibrosis, and several human and experimental nephritides. However, the role of this profibrotic factor in the vascular damage associated with hypertension is not well known. Objective. To study the role of CTGF in vascular alterations associated with hypertension in rats, as well as its possible interaction with aldosterone. Method. Male spontaneously hypertensive rats (SHR) were treated with 2 doses (30 and 100 mg/Kg/day) of the mineralocorticoid receptor antagonist eplerenone for 10 weeks. Normotensive rats (WKY) were used as a control group. At the end of the treatment, systolic blood pressure (SBP) and vascular reactivity in aortic rings were measured. In addition, vascular expression and protein levels of CTGF, as well as morphological lesions in the aorta, were evaluated. The direct effect of aldosterone on vascular smooth muscle cells was also studied. Results. SBP was higher in SHR than in WKY and only the high dose of eplerenone significantly reduced SBP. In the aorta of SHR, CTGF mRNA expression and protein levels were upregulated compared with WKY. Both doses of eplerenone similarly and significantly diminished CTGF upregulation. Endothelium-dependent relaxation was lower in SHR than in WKY and treatment with eplerenone normalized this response. Vessel area, lumen area and media area, as well as the media to lumen ratio, were significantly increased in SHR compared with WKY. Treatment with eplerenone reduced all the parameters studied and normalized the media to lumen ratio. Incubation of cultured vascular smooth muscle cells with aldosterone increased CTGF production in a dose-dependent manner. Conclusions. Aldosterone participates in both the functional and structural alterations associated with hypertension. CTGF is one of the factors implicated in the vascular fibrotic process associated with hypertension (AU)

Efecto de la atorvastatina sobre la expresión vascular de los PPAR en conejos dislipémicos / Effect of atorvastatin on vascular expression of PPAR in dyslipidemic rabbits

Introducción. La familia de los receptores activados por proliferadores de peroxisomas (PPAR) presenta efectos antiinflamatorios, antioxidantes así como efectos sobre el metabolismo lipídico y glucídico. Las estatinas presentan ciertos efectos parecidos a los PPAR, por lo que se ha sugerido que parte de sus acciones podrían estar mediadas por los PPAR. Objetivo. Evaluar el efecto de la dislipemia y del tratamiento con atorvastatina sobre la expresión vascular de los PPARa, b/d y g, la función endotelial y la lesión aterosclerótica. Material y método. Se utilizaron conejos macho New Zealand alimentados con una dieta con un 1% de colesterol con o sin tratamiento con atorvastatina (1 mg/kg/día) durante 10 semanas. Un grupo de animales alimentados con una dieta estándar se utilizó como un grupo control. Se evaluó la respuesta a la acetilcolina (10­9-10­5 mol/l) y al nitroprusiato sódico (10­10-10­6 mol/l) en la aorta. Se realizó el análisis morfométrico de la aorta, así como la expresión vascular de los PPARa, b/d y g por RT-PCR a tiempo real. Resultados. Los animales alimentados con una dieta con un 1% de colesterol presentaron concentraciones de colesterol total, colesterol unido a lipoproteínas de baja densidad (cLDL) y triglicéridos superiores a los de los conejos controles. La dislipemia se asoció con un engrosamiento de la íntima, una reducción de la relajación a la acetilcolina y una reducción de la expresión vascular de los PPARa y g. El tratamiento con atorvastatina normalizó las concentraciones de triglicéridos y redujo las de colesterol total y cLDL, aunque no fue capaz de normalizarlas. Asimismo, redujo el tamaño de la lesión aterosclerótica, y previno la reducción de la relajación a la acetilcolina y de la expresión de los PPAR. Ni la dislipemia ni el tratamiento con atorvastatina fueron capaces de modificar la expresión de los PPARb/d. Conclusiones. Estos datos sugieren que la dislipemia tiene un efecto diferencial sobre la expresión aórtica de los distintos PPAR, ya que reduce los PPARa y g y no altera los PPARb/d. El aumento de la expresión de los PPARa y g observado con el tratamiento con atorvastatina podría participar en los efectos antiaterogénicos ejercidos por ella (AU)

Introduction. The family of peroxisome proliferator-activated receptors (PPARs) displays anti-inflammatory and anti-oxidant effects, as well as some effects that act on lipid and glucose metabolism. Statins show certain effects similar to those of PPARs, and consequently it has been suggested that these drugs could exert their anti-atherogenic effects by means of PPAR modulation. Aim. To evaluate the effect of dyslipidemia and atorvastatin treatment on vascular expression of PPARa, b/d and g, endothelial function, and atherosclerotic lesions. Material and method. Male New Zealand rabbits were fed a 1% cholesterol-enriched diet with or without atorvastatin (1 mg/kg/day) for 10 weeks. A group of animals fed a standard diet was used as a control. At the end of the treatment, responses to acetylcholine (10­9-10­5 mol/l) and sodium nitroprusside were evaluated (10­10-10­6 mol/l). Morphometric analysis of the aorta was performed, as well as real time RT-PCT to measure vascular expression of PPARa, b/d and g. Results. Animals fed a cholesterol-enriched diet had higher levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides than controls. Dyslipidemia was associated with intimal thickening and reductions in acetylcholine relaxation and PPARa and g vascular expression. Atorvastatin treatment normalized triglyceride levels and reduced those of total cholesterol and LDL-cholesterol but was not able to normalize them. This drug also prevented reductions in acetylcholine relaxation and PPAR expression and reduced atherosclerotic lesion size. Neither dyslipidemia nor atorvastatin treatment modified PPARb/d expression. Conclusions. These data suggest that dyslipidemia exerts varying effects on aortic PPAR expression, reducing PPARa and g while not modifying PPARb/d. The increased PPARa and g expression observed with atorvastatin administration could mediate the anti-atherogenic effects exerted by this statin (AU)

[The influence of pressure and temperature on the behavior of the human aorta and carotid arteries]. / Influencia de la presión y la temperatura en el comportamiento de la aorta y las carótidas humanas.

INTRODUCTION AND OBJECTIVES: The thermomechanical behavior of human arteries is still not well characterized despite its importance for understanding arterial physiology, and for evaluating and improving surgical procedures. The aim of this study was to provide, for the first time, experimental data illustrating how the mechanical responses of two types of human artery -the carotid artery and the aorta- are affected by changes in temperature. METHODS: The mechanical properties of the arteries were derived in vitro from internal pressure-external diameter curves measured at four different temperatures (i.e., 17, 27, 37 and 42 degree C). Coefficients of expansion and stiffness were obtained by thermomechanical analysis. The condition of the arterial wall was determined histologically. RESULTS: The aorta and the carotid artery became slightly more compliant as the temperature increased. In both vessels, the coefficient of expansion depended critically on internal pressure. At low pressures, the coefficient of expansion was negative (i.e., the vessel contracted when heated), whereas close to a specific threshold pressure, which is different for each type of artery, the coefficient became positive. CONCLUSIONS: The mechanical behavior of arteries is affected by the combination of internal pressure and temperature. Consequently, the effect of this combination should be taken into account in clinical situations involving a change in temperature. Moreover, the strength of the effect depends on the type of artery under study. As a result, more detailed experimental data focusing on vessels of clinical interest are required.

Influencia de la presión y la temperatura en el comportamiento de la aorta y las carótidas humanas / The influence of pressure and temperature on the behavior of the human aorta and carotid arteries

Introducción y objetivos. La respuesta termomecánica de las arterias humanas es poco conocida a pesar de su importancia para la comprensión de la fisiología arterial, y para la evaluación y mejora de los procedimientos quirúrgicos. El objetivo de este trabajo es aportar por vez primera datos experimentales que muestren cómo se ve afectada la respuesta mecánica de dos tipos de arterias humanas ­aorta y carótida­ por los cambios de temperatura. Métodos. La respuesta mecánica de las arterias se ha obtenido in vitro a través de la medición de las curvas presión interior-diámetro exterior para 4 temperaturas (17, 27, 37 y 42 oC). Se ha realizado un análisis termomecánico para obtener los coeficientes de dilatación y la rigidez del material. El estado de la pared arterial se ha evaluado mediante análisis histológico. Resultados. Las arterias aorta y carótida aumentan ligeramente su flexibilidad con la temperatura. El coeficiente de dilatación de ambos vasos depende críticamente de la presión interior aplicada. A bajas presiones, el coeficiente de dilatación es negativo (el vaso se contrae cuando se calienta), mientras que por encima de cierta presión umbral ­distinta para cada tipo de arteria­ el coeficiente de dilatación se hace positivo. Conclusiones. El efecto combinado de la presión interior y la temperatura afecta al comportamiento de las arterias y, por ello, debe ser tenido en cuenta al abordar situaciones clínicas que impliquen cambios de temperatura. La intensidad de este efecto depende del tipo de arteria estudiada, lo que requiere la obtención de datos más detallados, centrados en los vasos de interés clínico

Introduction and objectives. The thermomechanical behavior of human arteries is still not well characterized despite its importance for understanding arterial physiology, and for evaluating and improving surgical procedures. The aim of this study was to provide, for the first time, experimental data illustrating how the mechanical responses of two types of human artery ­the carotid artery and the aorta­ are affected by changes in temperature. Methods. The mechanical properties of the arteries were derived in vitro from internal pressure­external diameter curves measured at four different temperatures (i.e., 17, 27, 37 and 42 oC). Coefficients of expansion and stiffness were obtained by thermomechanical analysis. The condition of the arterial wall was determined histologically. Results. The aorta and the carotid artery became slightly more compliant as the temperature increased. In both vessels, the coefficient of expansion depended critically on internal pressure. At low pressures, the coefficient of expansion was negative (i.e., the vessel contracted when heated), whereas close to a specific threshold pressure, which is different for each type of artery, the coefficient became positive. Conclusions. The mechanical behavior of arteries is affected by the combination of internal pressure and temperature. Consequently, the effect of this combination should be taken into account in clinical situations involving a change in temperature. Moreover, the strength of the effect depends on the type of artery under study. As a result, more detailed experimental data focusing on vessels of clinical interest are required

Interactions between aldosterone and connective tissue growth factor in vascular and renal damage in spontaneously hypertensive rats.

OBJECTIVE: The aim of the present study was to investigate possible inter-relationships between connective tissue growth factor (CTGF) and aldosterone in vascular and renal damage associated with hypertension. METHOD: Spontaneously hypertensive rats (SHR) were treated with two doses (100 and 30 mg/kg per day) of the mineralocorticoid receptor antagonist eplerenone, or with antihypertensive therapy (HHR) (20 mg/kg per day hydralazine + 7 mg/kg per day hydrochlorothiazide + 0.15 mg/kg per day reserpine). RESULTS: CTGF mRNA expression and protein levels in the aorta of SHR were upregulated (P < 0.05) compared with Wistar-Kyoto rats. Both doses of eplerenone similarly and significantly diminished CTGF upregulation, correlated with amelioration of aortic remodelling and endothelium-dependent relaxations. Only high-dose eplerenone and HHR significantly reduced arterial blood pressure. HHR treatment also diminished CTGF overexpression, suggesting a blood-pressure-mediated effect in CTGF regulation. This reduction, however, was lower (P < 0.05) than that produced by eplerenone (100 mg/kg per day). The direct effect of aldosterone on vascular smooth muscle cells was also studied. Incubation of cultured vascular smooth muscle cells with aldosterone increased CTGF production in a dose-related manner, but was reduced (P < 0.05) by the mineralocorticoid receptor antagonist spironolactone. Renal CTGF mRNA and protein levels were higher in SHR than in Wistar-Kyoto rats (P < 0.05), and were similarly diminished by all treatments (P < 0.05). CONCLUSIONS: These data show that aldosterone and haemodynamic stress from elevated blood pressure levels regulate vascular and renal CTGF in SHR. The results suggest that aldosterone, through CTGF stimulation, could participate in vascular and renal structural alterations associated with hypertension, describing a novel mechanism of aldosterone in hypertensive target organ damage.

[Acute coronary syndrome in infective endocarditis]. / Síndrome coronario agudo en la endocarditis infecciosa.

INTRODUCTION AND OBJECTIVES: To describe the clinical, microbiologic, echocardiographic characteristics, and disease progression in patients who experience an acute coronary syndrome during an episode of endocarditis. METHODS: The study included 586 consecutive patients who were diagnosed of infective endocarditis (481 left-sided) at one of five hospitals between 1995 and 2005. RESULTS: Overall, 14 patients (2.9%) had an acute coronary syndrome. Their mean age was 50 (17) years, and 50% had a prosthetic valve. For 11 episodes of endocarditis, laboratory cultures tested positive, with Staphylococcus aureus being the most frequently isolated microorganism. Vegetations were detected by transesophageal echography in 12 cases. The infection was located in the aortic valve in 12 cases. In the 14 patients, periannular complications were found more frequently (11 [78.6%] vs 172 [36.8%]; P=.03), and their size was greater than in other patients. Thirteen had moderate-to-severe valvular regurgitation. In most patients, acute coronary syndrome was an early complication of endocarditis. Myocardial ischemia was due to an embolism in three cases and to coronary artery compression in eight. During follow-up, patients with acute coronary syndrome had higher incidences of heart failure (6 [42.85%] vs 77 [16.48%]; P=.021), cardiogenic shock (5 [35.7%] vs 71 [15.2%]; P=.038), complete atrioventricular block (4 [28.57%] vs 43 [9.2%]; P=.039), and mortality (9 [64.29%] vs 151 [32.33%]; P=.019). CONCLUSIONS: Acute coronary syndrome is usually an early complication of infective endocarditis. It is associated with virulent microorganisms, aortic valve infection, severe valvular regurgitation, extensive periannular complications, and increased mortality. The most frequent cause of myocardial ischemia was coronary artery compression secondary to periannular complications.

Síndrome coronario agudo en la endocarditis infecciosa / Acute coronary syndrome in infective endocarditis

Introducción y objetivos. Describir las características epidemiológicas, clínicas, microbiológicas, ecocardiográficas y evolutivas de los pacientes con un síndrome coronario agudo en el seno de una endocarditis. Métodos. Hemos analizado 586 episodios de endocarditis (481 izquierdos) diagnosticados de forma consecutiva en 5 hospitales desde 1995 hasta 2005. Resultados. Hubo 14 pacientes (2,9%) con un síndrome coronario agudo, con una edad media de 50 ± 17 años. El 50% tenían una prótesis valvular. Los cultivos fueron positivos en 11 episodios y el germen aislado con más frecuencia fue Staphylococcus aureus. La ecocardiografía transesofágica detectó vegetaciones en 12 casos. La localización de la infección fue aórtica en 12 casos. Se documentaron con más frecuencia complicaciones perivalvulares (n = 11 [78,6%] frente a n = 172 [36,8%]; p = 0,03) y su tamaño fue mayor que el de los otros pacientes de la serie. Trece pacientes tuvieron insuficiencia valvular de moderada a severa. El síndrome coronario agudo se manifestó precozmente en la mayoría de los pacientes. El mecanismo de la isquemia fue embólico en 3 casos y por compresión coronaria en 8. Durante la evolución, los pacientes con síndrome coronario agudo tuvieron una mayor incidencia de insuficiencia cardiaca (n = 6 [42,85%] frente a n = 77 [16,48%]; p = 0,021), shock cardiogénico (n = 5 [35,7%] frente a n = 71 [15,2%]; p = 0,038) y bloqueo auriculoventricular (n = 4 [28,57%] frente a 43 [9,2%]; p = 0,039). La mortalidad fue también superior en estos pacientes (n = 9 [64,29%] frente a n = 151 [32,33%]; p = 0,019). Conclusiones. El síndrome coronario agudo es una complicación precoz de la endocarditis. Se asocia más a microorganismos virulentos, infección valvular aórtica, insuficiencia valvular severa, complicaciones perianulares de gran tamaño y elevada mortalidad. El mecanismo más frecuente fue la compresión coronaria secundaria a complicaciones perianulares

Introduction and objectives. To describe the clinical, microbiologic, echocardiographic characteristics, and disease progression in patients who experience an acute coronary syndrome during an episode of endocarditis. Methods. The study included 586 consecutive patients who were diagnosed of infective endocarditis (481 left-sided) at one of five hospitals between 1995 and 2005. Results. Overall, 14 patients (2.9%) had an acute coronary syndrome. Their mean age was 50 (17) years, and 50% had a prosthetic valve. For 11 episodes of endocarditis, laboratory cultures tested positive, with Staphylococcus aureus being the most frequently isolated microorganism. Vegetations were detected by transesophageal echography in 12 cases. The infection was located in the aortic valve in 12 cases. In the 14 patients, periannular complications were found more frequently (11 [78.6%] vs 172 [36.8%]; P=.03), and their size was greater than in other patients. Thirteen had moderate-to-severe valvular regurgitation. In most patients, acute coronary syndrome was an early complication of endocarditis. Myocardial ischemia was due to an embolism in three cases and to coronary artery compression in eight. During follow-up, patients with acute coronary syndrome had higher incidences of heart failure (6 [42.85%] vs 77 [16.48%]; P=.021), cardiogenic shock (5 [35.7%] vs 71 [15.2%]; P=.038), complete atrioventricular block (4 [28.57%] vs 43 [9.2%]; P=.039), and mortality (9 [64.29%] vs 151 [32.33%]; P=.019). Conclusions. Acute coronary syndrome is usually an early complication of infective endocarditis. It is associated with virulent microorganisms, aortic valve infection, severe valvular regurgitation, extensive periannular complications, and increased mortality. The most frequent cause of myocardial ischemia was coronary artery compression secondary to periannular complications

Lipid cartography of atherosclerotic plaque by cluster-TOF-SIMS imaging.

Several frozen vessels bearing atherosclerotic lesion were analysed by cluster TOF-SIMS (time-of-flight secondary ion mass spectrometry) to map their lipid (fatty acids, cholesterol, vitamin E, phosphatidic acids, phosphatidylinositols and triglycerides) content at a micrometric resolution.

Pathological effects of pulmonary vein beta-radiation in a swine model.

INTRODUCTION: Atrial fibrillation (AF) may be triggered by ectopic beats originating in sleeves of atrial myocardium entering the pulmonary veins (PVs). PV isolation by means of circumferential ostial or atrial radiofrequency ablation is an effective but also a difficult and long procedure, requiring extensive applications that can have serious potential complications. Our objective was to examine pathological effects of PV beta-radiation, particularly the ability to destroy PV myocardial sleeves without inducing PV stenosis and other unwanted effects, in order to establish its potential feasibility for the treatment of AF. METHODS AND RESULTS: Ten minipigs were studied. A phosphorus-32 source wire centered within a 2.5-mm diameter balloon catheter (Galileo III Intravascular Radiotherapy System, Guidant, Santa Clara, CA, USA) was used to deliver beta-radiation to the superior wall of the right PV trunk. Pathological analysis was performed either immediately after ablation (2 pigs) or 81 +/- 27 days later (8 pigs). Acute effects of PV beta-radiation consisted of endothelial denudation covered by white thrombus, elastic lamina disruption, and PV sleeve necrosis. Late effects consisted of mild focal neointimal hyperplasia that reduced the PV luminal area by only 1.3 +/- 1.8%, elastic lamina thickening, and PV sleeve fibrosis. Four of these 8 PVs were completely re-endothelized. Lesions were transmural in 6 of 10 radiated PVs and segmental, involving 28 +/- 7% of the right PV perimeter. CONCLUSION: Intravascular beta-radiation can induce transmural necrosis and fibrosis of PV myocardial sleeves without PV stenosis and other unwanted effects, which supports a potential usefulness of this energy source in the treatment of AF.

Cardiac metastasis from uterine leiomyosarcoma

Cardiac metastases are more frequent than primaryheart neoplasias. Nearly any malignant tumourmay metastasize to the heart, but the most commonare carcinomas rather than sarcomas. We report thecase of a patient who presented with heart metastasis6 years after resection of an uterine leiomyosarcoma.The patient died thirty months after surgicalresection without evidence of cardiac recurrence.Although cardiac metastases from uterine leiomyosarcomaare exceptional, they should be suspectedin the presence of suggestive symptoms, since theycan be associated with long survival after surgicaltreatment

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Role of connective tissue growth factor in vascular and renal damage associated with hypertension in rats. Interactions with angiotensin II.

We have evaluated the role of connective tissue growth factor (CTGF) in vascular and renal damage associated with hypertension and possible interactions with angiotensin II (Ang II). Spontaneously hypertensive rats (SHR) were treated with either the Ang II receptor antagonist candesartan (C;2 mg/Kg(-1)/day(-1)) or antihypertensive triple therapy (TT; in mg/Kg(-1)/day(-1);20 hydralazine +7 hydrochlorothiazide +0.15 reserpine) for 10 weeks. Wistar Kyoto rats were used as a normotensive control group. Hypertension was associated with an increase in aortic media area, media-to-lumen ratio and collagen density. Kidneys from SHR showed minimum renal alterations. Aorta and renal gene expression and immunostaining of CTGF were higher in SHR. Candesartan decreased arterial pressure, aortic media area, media-to-lumen ratio and collagen density. However, although arterial pressure decrease was comparable for both treatments, TT partially reduced these parameters. Candesartan-treated rats showed lower levels of vascular CTGF expression, aortic media area, media-to-lumen ratio and collagen density than TT-treated animals. Treatments improve renal damage and reduce renal gene expression and CTGF immunostaining in SHR in a similar manner. The results show that vascular and renal damage is associated with stimulation of CTGF gene and protein content. These results also might suggest that CTGF could be one downstream mediator of Ang II in hypertension-associated organ damage in SHR.