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Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that can modulate the behaviour of vascular smooth muscle cells and thus impact on the development of human atherosclerosis. Circulating plasma levels of ET-1 were measured from 82 patients with ischemic cardiomyopathy (ICM) and 42 healthy controls. A significant increase was found in plasma levels of ET-1 in the patients compared to the controls. These circulating levels of ET-1 were greater in patients with diabetes or involvement of several territories. Gene expression of pre-proET-1 and its receptors ETA and ETB was analyzed in the atheromatous plaques from carotid arteries (n = 8) and the internal mammary artery (IMA) (n = 8). Our group observed an increase in pre-proET-1 and ETA in IMA compared with the atheromatous plaques. Immunohistochemical studies in the atherosclerotic plaque showed that the expression of ET-1 was greater in the areas where the macrophages and lipid nucleus were located. Our findings in this group of patients with symptomatic vascular disease suggest that the endothelin system may play an important role in atherothrombosis.

A 78-year-old woman presented with an abrupt onset of chest pain and dyspnea. Fourteen years before admission, she had undergone aortic root and valve replacement with the Bentall-de Bono continuous-suture wrap-inclusion technique because of an aneurysm of the ascending aorta and severe aortic valve regurgitation. Physical examination revealed signs of congestive heart failure and poor peripheral perfusion. The admission radiograph (Figure 1) showed lung congestion predominantly in the right lung, bilateral pleural effusion, elevation of the left hemidiaphragm, tracheal shift to the right side, and aortic arch calcification. The ECG (Figure 2) revealed sinus tachycardia at 111 bpm, frequent premature atrial beats, and repolarization …

Endothelin (ET) is a potent vasoconstrictor peptide implicated in numerous human diseases, including ischemic cardiomyopathy (ICM). ET binds to receptors ET A and ET B . Specific ET receptors were characterized in left atria of patients with end-stage heart failure due to ischemic cardiomyopathy (ICM) ( n = 9) and healthy controls ( n = 9). Saturation assays revealed a K d and B max of 28 ± 8 pM and 87 ± 22 fmol mg −1 of protein, respectively, from healthy atria and 50 ± 9 pM and 162 ± 19 fmol mg −1 of protein, respectively, from diseased atria ( p A receptors using BQ123, 55% ± 5 and 66% ± 4 in healthy and diseased atria, respectively ( p B using BQ3020 was 55% ± 14 in healthy and 59% ± 10 in diseased atria. Microautoradiography studies showed a greater number of ET receptors, predominately ET A , existed in the myocardial layer of diseased atria compared with healthy atria. The percentage of occupied area was greater in the endocardium than the epicardium in diseased atria. These results showed an increase in the ET A /ET B receptor system in the failing human heart compared with the non-failing human heart.

Background and purpose: Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, might also suppress inflammatory components of atherogenesis. We have studied the effects of ezetimibe on two characteristics of atherosclerotic plaques (infiltrate and fibrosis) and on expression of inflammatory genes in a rabbit model of accelerated atherosclerosis. Experimental approach: Femoral atherosclerosis was induced by a combination of endothelial desiccation and atherogenic diet. Animals were randomized to ezetimibe (0.6 mg·kg−1·day−1), simvastatin (5 mg·kg−1·day−1), ezetimibe plus simvastatin or no treatment, still on atherogenic diet. A control group of rabbits received normolipidemic diet. Key results: Rabbits fed the normolipidemic diet showed normal plasma lipid levels. Either the normolipidemic diet or drug treatment reduced the intima/media ratio (normolipidemic diet: 22%, ezetimibe: 13%, simvastatin: 27%, ezetimibe + simvastatin: 28%), compared with rabbits with atherosclerosis. Ezetimibe also decreased macrophage content and monocyte chemoattractant protein-1 expression in atherosclerotic lesions. Furthermore, ezetimibe reduced the increased activity of nuclear factor κB in peripheral blood leucocytes and plasma C-reactive protein levels in rabbits with atherosclerosis. In THP-1 cells, ezetimibe decreased monocyte chemoattractant protein-1-induced monocyte migration. Importantly, the combination of ezetimibe with simvastatin was associated with a more significant reduction in plaque monocyte/macrophage content and some proinflammatory markers than observed with each drug alone. Conclusions and implications: Ezetimibe had beneficial effects both on atherosclerosis progression and plaque stabilization and showed additional anti-atherogenic benefits when combined with simvastatin. Its effect on monocyte migration provides a potentially beneficial action, in addition to its effects on lipids.

las nuevas tecnicas de imagen han permitido identificar, en la aorta el origen de embolias arteriales. La mayoria de estos trombos se localizan en aneurismas o estan adheridos a lesiones arterioscleroticas de aorta abdominal. Los trombos en aorta toracica son mucho menos frecuentes, especialmente en aortas aparentemente normales. En consecuencia, la historia natural y el tratamiento optimo de estas lesiones no estan bien definidos. El objetivo de este articulo es describir las caracteristicas clinicas, el tratamiento y la evolucion de 3 pacientes con trombosis de la aorta toracica y embolias arteriales. Se revisa la literatura disponible en relacion con esta afeccion y se aborda el diagnostico diferencial de estas lesiones.

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 3 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.

Introduccion El factor de crecimiento de tejido conectivo (CTGF) esta 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 profibrotico en el dano vascular asociado a hipertension no se conoce completamente. Objetivo Estudiar el posible papel del CTGF en el dano vascular asociado a hipertension en ratas, asi como la posible interaccion con la aldosterona. Metodo Se utilizaron ratas macho espontaneamente hipertensas (SHR) tratadas durante 10 semanas con 2 dosis de eplerenona, un antagonista selectivo de los receptores de mineralocorticoides (30 y 100 mg/kg/dia), y ratas normotensas (WKY) como grupo control. Al final del tratamiento se midio la presion arterial sistolica (PAS) y la reactividad vascular en anillos de aorta. Se determino la expresion vascular y los valores de proteina del CTGF, asi como la morfometria de la aorta. Se estudio tambien el efecto directo de la aldosterona en celulas de musculo liso vascular (CMLV). Resultados Las SHR presentaron unos valores de PAS mayores que las ratas controles WKY. Solo el tratamiento con la dosis alta de eplerenona redujo significativamente estos valores. La expresion vascular genica y los valores de proteinas del CTGF aumentaron significativamente en las SHR respecto a las WKY. El tratamiento con ambas dosis de eplerenona disminuyo significativamente estos parametros. La relajacion dependiente del endotelio fue menor en SHR que en WKY, y el tratamiento con eplerenona normalizo esta respuesta. Las areas del vaso, la luz y la media aumentaron significativamente en las SHR respecto a las WKY, asi como la relacion media/luz. El tratamiento con eplerenona redujo todas las areas estudiadas y normalizo la relacion media/luz. La incubacion de CMLV con aldosterona aumento la expresion de CTGF de forma dependiente de la dosis. Conclusiones La aldosterona participa en las alteraciones tanto funcionales como estructurales asociadas a la hipertension arterial. El CTGF es uno de los factores implicados en el proceso fibrotico vascular asociado a hipertension arterial.

Introduccion La familia de los receptors activados por proliferadores de peroxisomas (PPAR) presenta efectos antiinflamatorios, antioxidantes asi como efectos sobre el metabolismo lipidico y glucidico. Las estatinas presentan ciertos efectos parecidos a los PPAR, por lo que se ha sugerido que parte de sus acciones podrian estar mediadas por los PPAR. Objetivo Evaluar el efecto de la dislipemia y del tratamiento con atorvastatina sobre la expresion vascular de los PPARα, β/δ y γ, la funcion endotelial y la lesion aterosclerotica. Material y metodo Se utilizaron conejos macho New Zealand alimentados con una dieta con un 1% de colesterol con o sin tratamiento con atorvastatina (1 mg/kg/dia) durante 10 semanas. Un grupo de animales alimentados con una dieta estandar se utilizo como un grupo control. Se evaluo la respuesta a la acetilcolina (10−9-10−5 mol/l) y al nitroprusiato sodico (10−10-10−6 mol/l) en la aorta. Se realizo el analisis morfometrico de la aorta, asi como la expresion vascular de los PPARα, β/δ y γ 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 lipoproteinas de baja densidad (cLDL) y trigliceridos superiores a los de los conejos controles. La dislipemia se asocio con un engrosamiento de la intima, una reduccion de la relajacion a la acetilcolina y una reduccion de la expresion vascular de los PPARα y γ. El tratamiento con atorvastatina normalizo las concentraciones de trigliceridos y redujo las de colesterol total y cLDL, aunque no fue capaz de normalizarlas. Asimismo, redujo el tamano de la lesion aterosclerotica, y previno la reduccion de la relajacion a la acetilcolina y de la expresion de los PPAR. Ni la dislipemia ni el tratamiento con atorvastatina fueron capaces de modificar la expresion de los PPARβ/δ. Conclusiones Estos datos sugieren que la dislipemia tiene un efecto diferencial sobre la expresion aortica de los distintos PPAR, ya que reduce los PPARα y γ y no altera los PPARβ/δ. El aumento de la expresion de los PPARα y γ observado con el tratamiento con atorvastatina podria participar en los efectos antiaterogenicos ejercidos por ella.

Introduccion y objetivos La respuesta termomecanica de las arterias humanas es poco conocida a pesar de su importancia para la comprension de la fisiologia arterial, y para la evaluacion y mejora de los procedimientos quirurgicos. El objetivo de este trabajo es aportar por vez primera datos experimentales que muestren como se ve afectada la respuesta mecanica de dos tipos de arterias humanas –aorta y carotida– por los cambios de temperatura. Metodos La respuesta mecanica de las arterias se ha obtenido in vitro a traves de la medicion de las curves presion interior-diametro exterior para 4 temperaturas (17, 27, 37 y 42 °C). Se ha realizado un analisis termomecanico para obtener los coeficientes de dilatacion y la rigidez del material. El estado de la pared arterial se ha evaluado mediante analisis histologico. Resultados Las arterias aorta y carotida aumentan ligeramente su flexibilidad con la temperatura. El coeficiente de dilatacion de ambos vasos depende criticamente de la presion interior aplicada. A bajas presiones, el coeficiente de dilatacion es negativo (el vaso se contrae cuando se calienta), mientras que por encima de cierta presion umbral –distinta para cada tipo de arteria– el coeficiente de dilatacion se hace positivo. Conclusiones El efecto combinado de la presion interior y la temperatura afecta al comportamiento de las arterias y, por ello, debe ser tenido en cuenta al abordar situaciones clinicas que impliquen cambios de temperatura. La intensidad de este efecto depende del tipo de arteria estudiada, lo que requiere la obtencion de datos mas detallados, centrados en los vasos de interes clinico.

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.

Introduccion y objetivos Describir las caracteristicas epidemiologicas, clinicas, microbiologicas, ecocardiograficas y evolutivas de los pacientes con un sindrome coronario agudo en el seno de una endocarditis. Metodos 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 sindrome coronario agudo, con una edad media de 50 ± 17 anos. El 50% tenian una protesis valvular. Los cultivos fueron positivos en 11 episodios y el germen aislado con mas frecuencia fue Staphylococcus aureus. La ecocardiografia transesofagica detecto vegetaciones en 12 casos. La localizacion de la infeccion fue aortica en 12 casos. Se documentaron con mas frecuencia complicaciones perivalvulares (n = 11 [78,6%] frente a n = 172 [36,8%]; p = 0,03) y su tamano fue mayor que el de los otros pacientes de la serie. Trece pacientes tuvieron insuficiencia valvular de moderada a severa. El sindrome coronario agudo se manifesto precozmente en la mayoria de los pacientes. El mecanismo de la isquemia fue embolico en 3 casos y por compresion coronaria en 8. Durante la evolucion, los pacientes con sindrome coronario agudo tuvieron una mayor incidencia de insuficiencia cardiaca (n = 6 [42,85%] frente a n = 77 [16,48%]; p = 0,021), shock cardiogenico (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 tambien superior en estos pacientes (n = 9 [64,29%] frente a n = 151 [32,33%]; p = 0,019). Conclusiones El sindrome coronario agudo es una complicacion precoz de la endocarditis. Se asocia mas a microorganismos virulentos, infeccion valvular aortica, insuficiencia valvular severa, complicaciones perianulares de gran tamano y elevada mortalidad. El mecanismo mas frecuente fue la compresion coronaria secundaria a complicaciones perianulares.

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 (ie, 17, 27, 37, and 42 o 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 (ie, 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.

In the present study, we compared the effect of atorvastatin (1 mg·kg-1·day-1) and quinapril (0.5 mg·kg-1·day-1) alone or in combination on inflammatory markers, endothelial function, intimal thickening and fibrinolytic balance in rabbits fed with either a control diet or a diet containing 1% (v/v) cholesterol for 12 weeks. Atorvastatin alone or in combination partially prevented the increase in cholesterol plasma levels observed in rabbits fed with the cholesterol-rich diet, but did not modify blood pressure levels. Quinapril administration did not alter any of these parameters in any group. Hypercholesterolaemia increased plasma levels of interleukin-1β, interleukin-6, interferon-γ and C-reactive protein, reduced acetylcholine-induced relaxation and produced intimal thickening. Likewise, atherosclerotic rabbits had reduced plasma tissue-type plasminogen activator activity and D-dimer levels and an increase in plasminogen-activator inhibitor-1 activity. Both drugs enhanced acetylcholine-induced relaxation, reduced intimal thickening and improved fibrinolytic balance in atherosclerotic rabbits in a similar manner. Their combination did not induce additive effects on these parameters. However, only the combination of both drugs was able to prevent the increase in inflammatory markers induced by hypercholesterolaemia. In summary, these data suggest that quinapril and atorvastatin had comparable beneficial effects on the alterations of vascular function and structure as well as fibrinolytic balance in atherosclerotic rabbits. In addition, the combination of atorvastatin and quinapril exerts a synergistic effect on inflammatory markers, which individual treatment, at the doses used, was not able to modify.

Background Endothelins are important vasoconstrictors and cellular-growth promoters. ETA-specific antagonists have been shown to reduce neointimal response to injury in some experimental angioplasty models. However, there is little information on the effects of dual ETA/ETB receptor blockers, such as bosentan, on neointimal proliferation following experimental coronary angioplasty. Materials and methods Coronary injury was achieved by directional atherectomy in the left anterior descending artery of 20 pigs. Animals were randomly assigned to receive a daily dose of oral bosentan (30 mg kg−1) (group I, n= 10) or no treatment (group II, n= 10). At 4 weeks, arteries were processed for histomorphometry and endothelin characterization. Results Vessel injury score was similar among the two groups. Overall, a linear correlation was found between injury and neointimal development (r = 0·57, P= 0·01). This correlation had a lower slope in group I compared with group II (P

Autopsy has been one of the most important techniques for the development of modern medicine, mainly during the nineteenth century and the first half of last century. However, in the last few years, the number of autopsies performed in hospitals has dramatically decreased all over the world. This loss of interest can be attributed both to important advances in other diagnostic and therapeutic techniques and to the fear of malpractice suits. Several groups have tried to overcome this problem, developing different autopsy techniques, one of which is needle autopsy. Most authors using this technique have acknowledged that it is difficult to obtain material from certain organs and lesions, which makes its diagnostic reliability worse than that of conventional autopsy. To overcome this drawback, our team has recently developed a modification of needle autopsy, called ultrasonographic autopsy or echopsy, in which samples are obtained under ultrasonographic control. We report the results of the first 100 cases of echopsy performed in our hospital, comparing this technique with conventional autopsy performed on all the corpses. The concordance rate for the cause of death and the main pathological diagnosis between echopsy and classical autopsy was 83% in our series, which makes echopsy a feasible and reliable alternative to conventional autopsy in cases in which families refuse to give their consent for classical autopsy or in cases of infectious diseases.

Abstract —The effects of angiotensin (AT) 1 receptor antagonists on functional and morphological alterations associated with atherosclerosis are not well known. The current study was performed to examine the long-term effects of valsartan (3 or 10 mg/kg per day for 10 weeks) on endothelial function and structural changes in aorta from rabbits fed with either a control diet or a cholesterol-enriched diet. Rabbits fed with the cholesterol-rich diet showed higher ( P P P P 1 receptors, appears to play a key role in the development of the vascular functional and structural changes associated with hypercholesterolemia. AT 1 receptor antagonists, besides their antihypertensive effects, could be an important therapeutic tool to reduce the development of atherosclerosis.

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.

Objectives. This study sought to describe the ability of transesophageal echocardiography (TEE) to document the presence of penetrating atherosclerotic aortic ulcers and their complications. Background. TEE has greatly enhanced our ability to assess patients with suspected aortic disease. However, the utility of this technique in the diagnosis of penetrating atherosclerotic aortic ulcers is still undefined. Methods. TEE was performed prospectively in 194 patients to evaluate aortic disease. Twelve patients with the diagnosis of aortic ulcers or their complications were specifically studied. The diagnosis was confirmed by pathologic studies in six patients and by an additional diagnostic technique (angiography, computed tomography or magnetic resonance imaging) in the other six. All 12 patients were hypertensive and presented with chest or back pain; the mean age was 65 years (range 56 to 79). The initial working diagnosis was acute aortic dissection in nine patients. Aortic ulcers were located in the descending thoracic aorta in eight patients, the aortic arch in two and the ascending aorta in two. Results. TEE could detect aortic ulcers or their complications in 10 patients but failed to detect these lesions in the remaining 2 (1 with aortic ulcers in the distal ascending aorta and 1 with aortic ulcers in the aortic arch). In four patients, aortic ulcers were detected as a calcified focal outpouching of the aortic wall and were associated with concomitant aneurysmal dilation of the aorta in two patients and with a small localized intramural hematoma in one. TEE visualized a partially thrombosed pseudoaneurysm complicating an aortic ulcer in the descending thoracic aorta of two patients. Four patients had an aortic ulcer complicated by a “limited aortic dissection” in the descending aorta that could be detected by TEE. Five patients underwent operation, two because of aneurysmal dilation of the aorta and three because of aortic dissection; two patients died of aortic rupture; the remaining five did well (11-month follow-up) without operation. Conclusions. Aortic ulcers should be included in the differential diagnosis of chest or back pain, especially in elderly hypertensive patients. These ulcers and their complications may be recognized by TEE.

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 β-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.

A 58-year-old woman presented with a new rapidly progressive lesion distal to a stent. This lesion was treated with atherectomy through the stem in order to characterize it pathologically. The aggressive proliferative response discovered suggested that this unusually distal lesion was produced by the trauma of her previous angioplasty.

We report a case of a 77-year-old woman who had a rupture of the descending thoracic aorta as a complication of an atherosclerotic aortic plaque. Transesophageal echocardiography enabled the diagnosis of aortic rupture and was very useful in the patient's surgical management.

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.

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.

The term acute aortic syndrome (AAS), coined several years ago, is now widely recognised. In the light of new findings in aortic pathology and in an era when modern imaging techniques are widely available and interventional management of AAS is increasing, some morphological and diagnostic aspects of acute aortic pathology have been examined and the syndrome updated. This article provides a new, comprehensive overview of the pathology, diagnosis, evolution and management of patients with AAS. As acute aortic disease is the most common fatal condition in patients with chest pain, prompt recognition and treatment is of paramount importance.

During 241 consecutive percutaneous mitral valvotomy (PMV) procedures performed with the Inoue balloon, 16 patients (6.6%) developed severe mitral regurgitation (MR). Baseline clinical, echocardiographic (Doppler mitral valve area and Wilkins' score) and hemodynamic data were not different from those of patients without this complication. Severe MR occurred during the first inflation in 7 patients and after several stepwise inflations in 9. Although maximal balloon size was similar in both groups, unusual indentations and subvalvular inflations were more frequently observed in patients who developed severe MR. Early mitral valve replacement was required in 6 patients. All of them had a leaflet rupture either along the midportion (2 patients), along a commissure (4 patients), or both. Commissural calcium was present in 5 valves and 5 also had severe subvalvular involvement that had been underestimated by echocardiography. Of the 10 nonsurgically treated patients, 4 had chordal rupture by echocardiographic criteria, whereas in the remaining 6 the precise mechanism of MR could not be determined. During follow-up (11.4 ± 4 months, range 1 to 30), 1 patient required surgery for symptoms and the remaining 9 were symptomatically improved and free of left ventricular dilatation. In conclusion, severe MR complicated 6.6% of PMV procedures with the Inoue balloon, and its mechanism was leaflet or chordal rupture. Although one third of the patients required early mitral surgery, most of the remaining obtained midterm symptomatic benefit.

Se presenta un caso en que, tras una angioplastia aparentemente con exito en el contexto de un infarto agudo de miocardio e imagen de trombo intracoronario, no se logra restablecer un flujo coronario normal. Mediante aspiracion a traves del cateter guia se obtiene material hematico solido que el estudio anatomopatologico confirma como trombo hematico reciente, con la subsiguiente normalizacion del flujo. Tras ello, se completa el procedimiento con dilatacion con balon e implantacion de un stent intracoronario con exito. Se discuten las implicaciones diagnosticas y terapeuticas de este caso.

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 · s · −1 mm Hg −1 ), coronary resistance index (1.65±0.88 mm Hg · cm −1 · 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 (β=0.61, P =0.0009) and capillary density (β=−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.

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.

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.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.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.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.

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. Candesartantreated 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 exp Pression 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.

Supravalvular aortic stenosis is a rare complication of aortic dissection. We report on echocardiographic and magnetic resonance observations in 2 cases of aortic dissection with false lumen thrombosis of the ascending aorta and severe narrowing of the true lumen.

Cardiac metastases are more frequent than primary heart neoplasias. Nearly any malignant tumour may metastasize to the heart, but the most common are carcinomas rather than sarcomas. We report the case of a patient who presented with heart metastasis 6 years after resection of an uterine leiomyosarcoma. The patient died thirty months after surgical resection without evidence of cardiac recurrence. Although cardiac metastases from uterine leiomyosarcoma are exceptional, they should be suspected in the presence of suggestive symptoms, since they can be associated with long survival after surgical treatment.

Objective: Peroxisome proliferator-activated receptors (PPARs), key transcriptional regulators of lipid and energy metabolism in cardiomyocytes, have recently been proposed to modulate cardiovascular pathophysiological responses in experimental models. However, there is little information about the functional activity of PPARs in human heart failure. Aims: To investigate PPAR-α and -γ expression and activity, and the association with ET-1 production and fibrosis, in cardiac biopsies from patients with end-stage heart failure due to ischemic cardiomyopathy (ICM) in comparison and from non-failing donor hearts. All samples were obtained during cardiac transplantation. Methods and results: Morphological analysis (by Masson trichrome and image analysis) did not detect fibrosis in the left atrium from non-failing donors (NFLA) or from ICM patients (FLA). However, left ventricles from failing hearts (FLV) contained a greater number of fibrotic areas (NFLA: 3.21±1.15, FLA: 1.63±0.83, FLV: 14.5±3.45%; n=9, P

Acute dissection of the aorta is a life-threatening condition requiring immediate diagnosis and definitive treatment. Transoesophageal echocardiography may be considered the diagnostic procedure of choice in the assessment of patients with aortic dissection. A detailed morphological and functional study of the aorta must be obtained quickly. This report summarizes the echo-anatomical correlation of two distinct echocardiographic images of patients with aortic dissection.

Hypertrophic cardiomyopathy may cause congestive heart failure. Failure to recognise its predominant pathophysiologic mechanism may have adverse consequences. A 75 year old women was admitted for progressive dyspnoea and new onset atrial fibrillation. Propafenone was unsuccessful in restoring sinus rhythm. Digoxin and diuretics were started without clinical improvement, and captopril was added. A two dimensional (cross sectional) …

Relaxations to acetylcholine and contractions to acetylcholine in the presence of the nitric oxide (NO) synthesis inhibitor ( l - N G -nitroarginine methyl ester, l -NAME) were studied in aortic rings from rabbits fed either a control or a diet containing 0.5% cholesterol+14% coconut oil for 14 weeks and treated or not with atorvastatin (2.5 mg kg −1 day −1 ). Rings were incubated with the endothelin (ET A ) receptor antagonist BQ123, and/or the thromboxane A 2 (TXA 2 )/prostaglandin H 2 (PGH 2 ) receptor antagonist ifetroban. In rabbits, high cholesterol and triglyceride plasma levels were associated with intimal thickening and blunted acetylcholine-relaxation as compared with controls. By contrast, acetylcholine+ l -NAME response was higher. Incubation with either ifetroban or BQ123 increased acetylcholine-relaxation in both diet groups and it reduced the constrictor response only in dyslipidemic rabbits. Removal of endothelium reduced acetylcholine+ l -NAME contraction in dyslipidemic rabbits, although increased it in control animals. Atorvastatin treatment reduced plasma lipid levels and lesion size in dyslipidemic animals. Likewise, it prevented acetylcholine-relaxation reduction. In addition, atorvastatin reduced constrictor response in dyslipidemic rabbits but only in rings with endothelium. Incubation with either ifetroban or BQ123 did not further modify these responses in atorvastatin-treated animals in any group. These data suggest that ET and TXA 2 availabilities seem to participate in the endothelial dysfunction associated with dyslipidemia. Atorvastatin treatment reduces intimal thickening and improves endothelial dysfunction in rabbits. This effect seems to be a consequence of its ability to act on ET and TXA 2 systems.

Responses to both an endothelium-dependent (acetylcholine 10(-9)-10(-5) mol/l) and an endothelium-independent vasodilator (sodium nitroprusside 10(-10)-10(-6) mol/l) were studied in aortic rings from rabbits fed or not with a diet containing 0.5% cholesterol plus 14% coconut oil for 14 weeks and treated or not with atorvastatin (2.5 mg/kg/day). Morphometric and ultrastructure analyses were also performed. Rabbits fed the dyslipidemic diet presented higher plasma cholesterol and triglyceride concentrations than controls (P0.05). This was associated with intima-media thickening and, consequently, aortic stenosis (29 +/- 3%) since vessel cross-sectional area did not change. Endothelial cells presented numerous alterations in dyslipidemic rabbits. Atorvastatin treatment only reduced plasma levels in dyslipidemic rabbits (P0.05), which were nevertheless higher than those of controls. In addition, it prevented the reduction in acetylcholine relaxation in hypercholesterolemic animals. Atorvastatin administration also enhanced the response to acetylcholine in rabbits fed a control diet. Likewise, atorvastatin treatment reduced lesion area and consequently increased aortic lumen in dyslipidemic rabbits but did not modify media thickening. It also prevented the majority of the ultrastructural changes observed in endothelial cells. In conclusion, chronic atorvastatin treatment exerts a protective role in vascular function, structure and ultrastructure even in the presence of high cholesterol and triglyceride plasma levels.

Abstract —The mechanisms involved in the blockade of proliferation in confluent endothelial cells are insufficiently understood. In this regard, the continuity of intercellular junctions appears to be critical to the regulation of endothelial monolayer cell growth. The present study examined the hypothesis that the disruption of the intercellular adherens junctions will trigger both endothelial cell proliferation and autocrine production of growth factors. With this purpose, we assessed the changes in growth, death resistance, and expression of vascular endothelial growth factor (VEGF) under conditions of disruption of the intercellular junctions between endothelial cells. Disruption of cell junctions was produced by means of a specific anti–vascular endothelial cadherin monoclonal antibody, EGTA, or cytochalasin D. Our results disclosed that these maneuvers induce an increase in VEGF mRNA production, with transcription of the 121–, 165–, and 189–amino acid isoforms of VEGF. Further evidence of the relationship between endothelial cells monolayer continuity and VEGF protein expression was obtained by the demonstration of an increase in VEGF protein, as determined by Western blot, induced by the aforementioned maneuvers, as well as by immunocytochemical detection of increased VEGF staining in the areas surrounding a mechanical endothelial injury and in endothelial cells at subconfluence. In functional terms, the autocrine expression of VEGF was associated with growth-promoting and cytoprotective effects, as assessed by [ 3 H]thymidine uptake, 51 Cr release, and flow cytometry. In conclusion, our results reveal that disruption of homophilic interendothelial junctions induces VEGF expression. Under these conditions, autocrine VEGF appears to have a relevant role in death inhibition and proliferation of endothelial cells.

This study describes the clinical, anatomic, echocardiographic, and Doppler features of 13 patients with mitral valve aneurysms. Eleven patients had definitive criteria for infective endocarditis. Transesophageal echocardiography was superior to conventional echocardiography in detecting and assessing aneurysms. Patients with heart failure required surgery. Echocardiographic detection of this lesion should not be, by itself, an immediate surgical indication.

Paraganglioma, also referred to as pheochromocytoma when functionally active, is a rare tumor thought to arise from the neuroectodermally derived paraganglionic cells that are dispersed widely along the autonomic ganglia. Mediastinal localization is very rare and the clinical presentation is variable. In most cases, hypertension due to catecholamine excess is the main clinical manifestation; however, the majority of these tumors are asymptomatic. A 36-year-old woman presented to her general practitioner with wheezing and dyspnea on exercise. Asthma was diagnosed, and she was treated with inhaled administration of a corticosteroid and a β2-agonist. Chest …

Background Acute aortic dissection is a cardiovascular emergency that requires prompt diagnosis and treatment. Transesophageal echocardiography is the current standard diagnostic imaging modality in many medical centers. Aortic intramural hematoma is a variant of aortic dissection whose natural history and prognosis have not been well studied. We performed transesophageal echocardiography in patients with aortic intramural hematoma to determine the echocardiographic characteristics and echocardiographic evolution of this lesion, impact on patient management, and patient outcome. Methods and Results Twenty-one consecutive patients with aortic intramural hematoma confirmed anatomically (four patients) or with an additional diagnostic imaging technique (17 patients) underwent a transesophageal echocardiographic examination. Fifteen patients with longstanding hypertension had chest or back pain, and the intramural hematoma was visualized in the ascending aorta ( n = 4), along the whole aorta ( n = 4), in the descending aorta ( n = 6), or in the aortic arch ( n = 1). The thickening of the aortic wall was crescentic. Patients with ascending aortic intramural hematoma had the following results: two patients died suddenly, three patients underwent surgery because of increased aortic wall thickening (one patient) or secondary intimal tear (two patients), and the remaining three patients had regression of the hematoma. Patients with hematoma confined to the descending aorta and the patient with aortic arch involvement ( n = 7) had a different result: one patient died from aortic rupture and the remaining six patients did well. Six patients had a traumatic aortic injury, and the intramural hematoma was located along the descending thoracic aorta. The thickening of the aortic wall was circular in five patients and crescentic in one. Three of these patients had normalized thickness of the aortic wall on follow-up transesophageal echocardiographic studies. The other three patients died from multiorgan system failure. Aortography showed a reduction of the diameter of the aortic lumen in four patients; diameter in the remaining 17 patients was normal. Conclusions Aortic intramural hematoma can be detected and monitored by transesophageal echocardiography but not by aortography. Two types of aortic intramural hematoma can be distinguished: (1) traumatic of good prognosis and (2) nontraumatic, which can be an early stage of the classic aortic dissection, with bad prognosis in cases involving the ascending aorta. (Am Heart J 1997;134:495-507.)