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Trypanosoma cruzi parasites are only rarely identified in conventional histological sections of hearts from chronic chagasic patients. This finding suggests that T. cruzi plays no important direct role in the chronic myocarditis that accordingly has been considered mainly an autoimmune process. We reinvestigated this issue using a polyclonal anti-T. cruzi antibody serum to map immunohistochemically the T. cruzi antigen(s) in 9 different regions of 8 necropsy hearts and 24 septal fragments from 24 hearts from chronic chagasic patients. T. cruzi antigen(s) were identified in 7 (87%) of the 8 mapped hearts and in 14 (58%) of the 24 septal fragments. There was a statistically significant correlation between the presence of T. cruzi antigen(s) and moderate or severe inflammatory infiltrate (p = 0.005). When staining revealed amastigotes within intact myocardial fibers, there was no surrounding inflammatory infiltrate. However, when T. cruzi antigen(s) were found in macrophages either as amastigotes, diffusely in the macrophages cytoplasm, or free in the interstitium as round structures similar to amastigotes, there was a heavy inflammatory infiltrate. In the case in which no parasite was detected, a mild inflammatory infiltrate was present in the myocardium. Foci of fibrosis did not stain for T. cruzi antigen. These findings do not exclude a role of autoimmunity in chronic chagasic cardiopathy. However, the striking correlation between the presence of T. cruzi antigen(s) with the severity of site of the inflammatory infiltrate supports a direct role for the parasite in the perpetuation of myocardial inflammation in Chagas' disease. The destruction of microvessels and occasional endothelial cells with parasitism among dense inflammatory infiltrate favors the concept that microcirculatory injury, induced by T. cruzi, also contributes to the lesions of chronic Chagas' disease.

Outer mitochondrial membrane (OMM) rupture was first noted in isolated mitochondria in which the inner mitochondrial membrane (IMM) had lost its selective permeability. This phenomenon referred to as mitochondrial permeability transition (MPT) refers to a permeabilized inner membrane that originates a large swelling in the mitochondrial matrix, which distends the outer membrane until it ruptures. Here, we have expanded previous electron microscopic observations that in apoptotic cells, OMM rupture is not caused by a membrane stretching promoted by a markedly swollen matrix. It is shown that the widths of the ruptured regions of the OMM vary from 6 to 250 nm. Independent of the perforation size, herniation of the mitochondrial matrix appeared to have resulted in pushing the IMM through the perforation. A large, long focal herniation of the mitochondrial matrix, covered with the IMM, was associated with a rupture of the OMM that was as small as 6 nm. Contextually, the collapse of the selective permeability of the IMM may precede or follow the release of the mitochondrial proteins of the intermembrane space into the cytoplasm. When the MPT is a late event, exit of the intermembrane space proteins to the cytoplasm is unimpeded and occurs through channels that transverse the outer membrane, because so far, the inner membrane is impermeable. No channel within the outer membrane can expose to the cytoplasm a permeable inner membrane, because it would serve as a conduit for local herniation of the mitochondrial matrix. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.

Thinning of myocardial segments, mainly at the apex and basal posterior region of left ventricle, are frequent lesions in chronic chagasic cardiopathy (CCC), but still without a well determined etiology. Previously we found severe myocardial microvascular dilatation that could cause ischemia in watershed regions. In this study we analyzed whether narrowness in epicardial coronary arteries in CCC might explain these thinned ventricular lesions. Two groups of dilated hearts with similar weights were compared: eleven hearts from patients with CCC versus four hearts from patients with dilated cardiomyopathy (IDCM). As normal controls we studied three non dilated normal weight hearts. There were no atherosclerotic plaques in the main branches of epicardial coronary arteries and cross-sectional luminal areas of proximal and distal segments were histologically measured. It was found that CCC hearts presented a lower mean luminal area in the right coronary artery (RCA) branch than IDCM, in proximal (4.3 ± 1.4 vs 6.6 ± 2.0 mm2; p= 0.02) and in distal (1.6 ± 1.0 vs 3.4 ± 0.9 mm²; p= 0.01) segments, with no statistical differences with normal hearts (2.7 ± 1.3 and 1.5 ± 0.3 mm²) in proximal (p= 0.2) and distal (p=0.11) sections. In conclusion thinning of ventricular wall in CCC patients seems to be ischemic lesions in the peripheral territory irrigated by the right coronary artery, possibly due to a steal phenomenon by the left coronary, induced by micro vessels dilatation Adelgazamientos segmentares del miocardio son frecuentes lesiones en la cardiomiopatía crónica chagásica (CCC), principalmente en el ápice de la región posterior del ventrículo izquierdo, cuya etiopatogenia todavía no está bien conocida. En trabajos anteriores se observó intensa dilatación de la micro circulación que podría llevar a isquemia en regiones de irrigaciones limítrofes. Este estudio analizó si estrechez de las arterias epicárdicas in CCC podrían explicar las lesiones de adelgazamientos ventriculares. Se compararon 2 grupos de corazones con pesos semejantes: 11 corazones de pacientes con CCC versus 4 corazones de pacientes con cardiomiopatia dilatada idiopática (IDCM). Como controles normales fueran estudiados 3 corazones no dilatados y con pesos normales. No estuvieron presentes placas ateroscleróticas en los principales ramos de las arterias coronarias epicárdicas. Las áreas de lumen en cortes transversales de los segmentos proximales e distales arteriales fueran medidas por histología. Los corazones con CCC mostraron una media de lumen menor en el ramo de la coronaria derecha que en los con IDCM, tanto en los segmentos proximales (4,3 ± 1,4 vs 6,6 ± 2,0 mm2; p= 0,02) como en los distales (1, 6 ± 1, 0 vs 3,4 ± 0,9 mm²; p= 0,01) y ninguna diferencia estadística fue observada cuando se compararon con los corazones normales (2,7 ± 1,3 vs 1,5 ± 0,3 mm²) tanto proximal (p= 0,2) como distal (p=0,11). Adelgazamientos ventriculares en pacientes con CCC parecen ser lesiones isquémicas en territorios distales, irrigados por la arteria coronaria derecha, posiblemente por un fenómeno de sustracción por la coronaria izquierda, debido a vasodilatación de micro circulación

We appreciate Dr Henrikson’s interest in our study1 and the opportunity to clarify several issues. Dr Henrikson had a very precise observation concerning the electrocardiogram, and we agree with the comments made. Indeed, it was a normofunctioning dual-chamber pacemaker, and the electrocardiogram was taken just before open heart surgery, with the pacemaker programmed to asynchronous ventricular pacing mode considering atrial lead manipulation. Moreover, in our article, we report a novel agent for implantable pacemaker infection in a patient with persistent bacteremia despite the fact that blood cultures were all negative, as highlighted by Dr Henrikson. Most cases of pacemaker lead infections are due to pathogens from the skin flora, with positive blood culture ranging in the literature from 80% to 100% of the cases. Making a parallel with heart valves in the human, there are many causes of culture-negative endocarditis. The causative agents of culture-negative endocarditis in the heart are fastidious bacteria (Bartonella quintana, Coxiella burnetii, or brucella species), fungi, and the usual organisms (mainly streptococci) found in patients who have received antibiotic treatment before blood samples are obtained for culture.2 Thus, we present here another possible etiology in this context, now related to pacemaker infections. While these fastidious bacteria yield negative hemocultures requiring different diagnostic approaches such as serology, in the case of microsporidium, electron microscopy is fundamental and should be complemented by polymerase chain reaction.1 Dr Henrikson also pointed out that no signs of endocarditis were present even though a large vegetation was disclosed. Pacemaker endocarditis may be limited to the pacemaker lead or involve the cardiac valves, generally the tricuspid, which can be demonstrated by the echocardiogram or intraoperatively. In our case there was no vegetation in this valve by both methods, but the mass entailed in valve insufficiency, present in 25% of the cases in one series.3 We cannot rule out that microscopic endocarditis was present because no biopsy specimens were taken from the valve. Nonetheless, the good clinical outcome after a long-term follow-up period makes this possibility unlikely.

The infection developed by Wistar Furth rats inoculated with the Y strain of Trypanosoma cruzi was the experimental model used in our study. The results showed that this infection altered considerably the CD4/CD8 lymphocyte subset ratio and the natural cytotoxic activity of mononuclear cells in the spleen, blood, and myocardial tissue. Concomitantly, an expansion of the number of cells expressing major histocompatibility complex (MHC) class II antigens was observed, as well as spontaneous development of high levels of blast cells, mainly in the spleen. The inflammatory infiltration of the myocardium, made up essentially of CD8+ cells (cytotoxic/suppressor T cells, natural killer cells), was initially found at 9 days postinfection, spread continuously, and was observed until the death of the animals at about 18 days postinfection. T. cruzi infection also enhanced the natural killer activity of mononuclear cells in the blood, spleen, and myocardium. Sorting these cells by affinity columns showed that the natural killer function was performed exclusively by the CD8+ population, which did not express MHC class II antigens. It was shown that the polyclonal T-lymphocyte activation induced by T. cruzi infection results in a wide distribution of CD8+ cells with enhanced natural cytotoxic activity in the spleen, blood, and cardiac tissue.

ObjectivesWe sought to determine whether the quantitative assessment of myocardial fibrosis (MF), either by histopathology or by contrast-enhanced magnetic resonance imaging (ce-MRI), could help predict long-term survival after aortic valve replacement.BackgroundSevere aortic valve disease is characterized by progressive accumulation of interstitial MF.MethodsFifty-four patients scheduled to undergo aortic valve replacement were examined by ce-MRI. Delayed-enhanced images were used for the quantitative assessment of MF. In addition, interstitial MF was quantified by histological analysis of myocardial samples obtained during open-heart surgery and stained with picrosirius red. The ce-MRI study was repeated 27 ± 22 months after surgery to assess left ventricular functional improvement, and all patients were followed for 52 ± 17 months to evaluate long-term survival.ResultsThere was a good correlation between the amount of MF measured by histopathology and by ce-MRI (r = 0.69, p < 0.001). In addition, the amount of MF demonstrated a significant inverse correlation with the degree of left ventricular functional improvement after surgery (r = −0.42, p = 0.04 for histopathology; r = −0.47, p = 0.02 for ce-MRI). Kaplan-Meier analyses revealed that higher degrees of MF accumulation were associated with worse long-term survival (chi-square = 6.32, p = 0.01 for histopathology; chi-square = 5.85, p = 0.02 for ce-MRI). On multivariate Cox regression analyses, patient age and the amount of MF were found to be independent predictors of all-cause mortality.ConclusionsThe amount of MF, either by histopathology or by ce-MRI, is associated with the degree of left ventricular functional improvement and all-cause mortality late after aortic valve replacement in patients with severe aortic valve disease.

Rupture of abdominal aortic aneurysm (AAA) is a poorly understood phenomenon. Some aneurysms rupture as they grow larger, while many very large ones do not. There have been numerous reports on the failure properties of unruptured AAA [1], but similar data on ruptured AAA is scarce. Some reports suggest that greater pressure-induced tension in the AAA wall may predispose some to rupture [1]. But what of failure properties? It is conceivable that aneurysms which rupture are globally weaker than ones that do not or perhaps have very localized weak spots. Such key issues have not been explored because of lack of specimens from ruptured AAA. In this exploratory study between clinical and engineering investigators, unruptured and ruptured AAA were wholly harvested from fresh cadavers and the regional variations in wall thickness, mechanical properties and cellular content were compared.Copyright © 2009 by ASME

A 60-year-old white man was admitted with a 2-week history of shivering and fever (38°C). He had had a dual-chamber pacemaker implanted in 1996 because of complete atrioventricular block, with an elective pulse generator replaced 3 months before admission. Medications taken on a daily basis included amiodarone for atrial fibrillation rhythm control and atenolol for hypertension. His blood pressure was normal; his heart rate was 80 bpm; and he was febrile (38.5°C). Chest auscultation revealed a systolic murmur at the left and right sternal borders with respiratory shifting in the heart sound, not previously described in this patient. ECG showed a normally functioning pacemaker (Figure 1). Chest x-ray was normal (Figure 2), as were renal function and differential white cell count. Figure 1. Twelve-lead surface ECG showed a normally functioning dual-chamber pacemaker. Figure 2. A, Frontal anterior-posterior chest x-ray showed a pacemaker in the right infraclavicular region with no other abnormality. B, Normal frontal posterior-anterior chest x-ray after surgical intervention. Endocarditis was confirmed by a transesophageal echocardiography …

Study objective — The aim was to investigate alterations in sulphated glycosaminoglycans in aortic dissection. Design — Aortic fragments were taken from 10 patients within the first 3 d after onset of symptoms of aortic dissection and from nine age matched patients with no aortic disease. Sulphated glycosaminoglycans were analysed and quantified by agarose gel electrophoresis and densitometry after degradation with specific enzymes. Measurements and main results — The amount of chondroitin sulphate was similar (7.14 ν 7.60 mg·g−1 of dry tissue, n = 10, p>0.5) in patients with dissection and in the control group. Total sulphated glycosaminoglycan content was decreased (11.51 ν 14.26 mg·g−1 of dry tissue, n = 10, p

Background Chamydophila pneumoniae (CP) and/or Mycoplasma pneumoniae (MP) are two bacteria detected in vulnerable atheromas. In this study we aimed to analyze whether CP and/or MP aggravates atherosclerosis induced by cholesterol-enriched diet in C57BL/6 apoE KO male mice. Thirty male apoE KO mice aged eight weeks fed by a diet containing 1% cholesterol until 32 weeks of age were divided into four groups: the first was inoculated with CP (n = 7), the second with MP (n = 12), the third with both CP + MP (n = 5), and the fourth with saline (sham n = 6). The animals were re-inoculated at 36 weeks of age, and sacrificed at 40 weeks of age. Two ascending aorta and one aortic arch segments were sampled. In the most severely obstructed segment, vessel diameter, plaque height, percentage of luminal obstruction and the degree of adventitial inflammation were analyzed. The plaque area/intimal surface ratio was obtained by measuring all three segments. The adventitial inflammation was semiquantified (0 absent, 1 mild, 2 moderate, and 3 diffuse). Results The mean and standard deviation of plaque height, % luminal obstruction, external diameter, the plaque area/intimal surface ratio and the adventitial inflammation values are the following for each group: MP (0.20 +/- 0.12 mm, 69 +/- 26%, 0.38 +/- 0.11 mm, 0.04 +/- 0.04 and 0.22 +/- 0.67), CP (0.23 +/- 0.08 mm, 90 +/- 26%, 0.37 +/- 0.08 mm, 0.04 +/- 0.03, and 0.44 +/- 0.53), MP + CP (18 +/- 0.08 mm, 84 +/- 4.0%, 0.35 +/- 0.25 mm, 0.03 +/- 0.03 and 1.33 +/- 0.82) and sham (0.08 +/- 0.09 mm, 42 +/- 46%, 0.30 +/- 0.10 mm, 0.02 +/- 0.03 and 0.71 ± 0.76). A wider area of plaque/intimal surface was observed in MP + CP inoculated groups (p = 0.07 and 0.06) as well as an increased plaque height in CP (p = 0.01) in comparison with sham group. There was also an increased luminal obstruction (p = 0.047) in CP inoculated group in comparison to sham group. Adventitial inflammation in MP + CP inoculated group was higher than MP, CP and the sham groups (p = 0.02). Conclusion Inoculation of CP, MP or both agents in C57BL/6 apoE KO male mice caused aggravation of experimental atherosclerosis induced by cholesterol-enriched diet, with distinct characteristics. CP inoculation increased the plaque height with positive vessel remodeling and co-inoculation of MP + CP caused the highest adventitial inflammation measures.

This study aims to analyze the embolic activity in patients with calcified aortic stenosis who underwent aortic valve replacement using intra-aortic filtration with an EMBOL-X System device (Edwards Lifesciences Inc., Mountain View, CA, USA).From January 2007 to July 2007, 13 consecutive patients with calcified aortic stenosis, who underwent isolated aortic valve replacement using intra-aortic filtration by an EMBOL-X System for 5 minutes after aortic clamp release, were evaluated. Mean patient age was 63.7 years (range 34 to 79 years) and 61.5% were female. The mean bypass time was 60.2 +/- 7.5 minutes (range 45 to 72 minutes) and the mean cross-clamp time was 50 +/- 7.5 minutes (range 35 to 63 minutes). Following removal, each filter was fixed in formalin and analyzed macroscopically with the captured fragments being counted. Histological examinations of the captured material were performed.There were no strokes or gross neurological events. There were no cases of postoperative renal failure. No deaths were reported during hospitalization. Particulate emboli were found in five (38.5%) of the filters. On histological analysis of the particulate emboli captured, two (40%) contained fibrin, two (40%) presented conjunctive tissue, one (20%) contained red blood cells and in one it was not possible to determine the nature of the particulates captured.The EMBOL-X System device was effective in particulate emboli capture in aortic valve replacement surgery of patients with calcified aortic stenosis.

FUNDAMENTO: Ainda hoje os casos de amiloidose cardíaca, em sua maioria, não são diagnosticados. OBJETIVO: Revelar fatores relacionados à dificuldade no diagnóstico de amiloidose. MÉTODOS: Comparação entre os dados clínicos, eletrocardiográficos e ecocardiográficos de 17 pacientes nos quais a amiloidose foi detectada apenas à necrópsia (grupo I) e os de outros 9, nos quais a doença foi percebida em vida (grupo II). As variáveis quantitativas foram avaliadas pelo teste t e as qualitativas, pelo teste exato de Fisher, com nível de significância de p < 0,05. RESULTADOS: Houve diferenças quanto a idade (grupo I: 75,29 + 11,61 anos; grupo II: 58,67 + 11,07 anos), associação com outra doença cardíaca (grupo I: 52,94%; grupo II: 0%), baixa voltagem à eletrocardiografia (grupo I: 17,65%; grupo II: 66,67%) e disfunção diastólica à ecocardiografia (grupo I: 7,69%; grupo II: 62,50%). Algum grau de espessamento da parede ventricular esquerda ("hipertrofia") foi encontrado em 75% dos casos de diagnóstico post-mortem e em 100% dos casos in vivo, porém a espessura da parede foi menor no grupo I (parede livre: 1,20 + 0,28 cm no grupo I vs. 1,53 + 0,18 cm no grupo II). Disfunção sistólica estava presente em 57,89% dos casos, sem diferença significativa entre os grupos. CONCLUSÃO: A amiloidose é diagnosticada quando os padrões clínico, eletrocardiográfico e ecocardiográfico são "típicos", mas na maioria dos casos o quadro não é assim, especialmente em idosos, em decorrência de associação com outras doenças, de falta de disfunção diastólica à ecocardiografia e de hipertrofia de grau leve. BACKGROUND: Currently, many cases of heart amyloidosis still fail to be diagnosed. OBJECTIVE: To disclose factors related to the difficulty in attaining the diagnosis of cardiac amyloidosis. METHODS: We compared the clinical, electrocardiographic and echocardiographic data of 17 patients in whom amyloidosis was diagnosed only at the necropsy (group I) with data from 9 patients in whom the disease was diagnosed in life (group II). The quantitative variables were compared by t-test and qualitative ones by Fisher's exact test. Significance was set at p

This work is a detailed study of the relevance of three sets of criteria to define myocarditis: Dallas meeting criterion, Edwards criterion and Dallas meeting criterion modified by the authors. Two groups were evaluated: normal autopsied hearts and endomyocardial biopsy from chronic chagasic patients at high risk of having myocarditis. Furthermore, endomyocardial biopsies from patients with dilated cardiomyopathy (DCM) were also evaluated . Applying the Edwards criterion, incidences of myocarditis in normal and chagasic hearts were 0% and 67% while with Dallas meeting criterion they were 0% and 42% and using our criterion the incidences were 0% and 92% respectively. In endomyocardial biopsies from DCM patients, the incidence of myocarditis was 7% with Edwards criterion, 22% with Dallas meeting and 33% with the authors own criterion. The authors concluded that their criterion, which defines myocarditis as the presence of inflammatory mononuclear cells enclosing more than 2 lymphocytes/400X aggregated to the cardiac fiber sarcolemma, is the most appropriate criterion of the three. Myocarditis was found in 33% of the 27 endomyocardial biopsy specimens from patients with DCM.

Background Sustained β-adrenoreceptor activation promotes cardiac hypertrophy and cellular injury. Aims To evaluate the cardioprotective effect of exercise on damage induced by β-adrenergic hyperactivity. Methods Male Wistar rats were randomised into four groups (n=8 per group): sedentary non-treated control (C), sedentary treated with isoproterenol 0.3 mg/kg/day administered subcutaneously for 8 days (I), exercised non-treated (E) and exercised plus isoproterenol administered during the last eight days of exercise (IE). Exercised animals ran on a treadmill for 1 h daily 6 times a week for 13 weeks. Results Isoproterenol caused increases in left ventricle (LV) wet and dry weight/body weight ratio, LV water content and cardiomyocyte transverse diameter. Additionally, isoproterenol induced severe cellular lesions, necrosis, and apoptosis, increased collagen content and reduced capillary and fibre fractional areas. Notably, all of these abnormalities were completely prevented by exercise. Conclusion Our data have demonstrated that complete cardioprotection is possible through exercise training; by preventing β-adrenergic hyperactivity-induced cardiac hypertrophy and structural injury.

Currently, many cases of heart amyloidosis still fail to be diagnosed.To disclose factors related to the difficulty in attaining the diagnosis of cardiac amyloidosis.We compared the clinical, electrocardiographic and echocardiographic data of 17 patients in whom amyloidosis was diagnosed only at the necropsy (group I) with data from 9 patients in whom the disease was diagnosed in life (group II). The quantitative variables were compared by t-test and qualitative ones by Fisher's exact test. Significance was set at por = 0.05.The two groups showed differences regarding age (group I: 75.29 +/- 11.61, group II: 58.67 +/- 11.07 years), association with other cardiac disease (group I: 52.94%, group II: 0%), low voltage at the ECG (group I: 17.65%, group II: 66.67%), and diastolic dysfunction at the echocardiogram (group I: 7.69%, group II: 62.50%). Some degree of left ventricular thickening was found in 75% of necropsy cases and 100% of controls (p=0.23), but wall thickness was lower in group I (free left ventricular wall: 1.20 +/- 0.28 cm versus 1.53 +/- 0.18 cm in group II, p=0.01). Systolic dysfunction was present in 57.89% of the cases, without significant difference between the groups.Amyloidosis is diagnosed when the clinical, ECG, and echocardiogram patterns are "typical", but most of the cases fail to be diagnosed, especially in elderly people, due to the association with other cardiac diseases, lack of diastolic dysfunction at the echocardiogram and only a slightly thickened ventricular wall.

PURPOSE: Vulnerable plaques are characterized by a myxoid matrix, necrotic lipidic core, reactive oxygen species, and high levels of microorganisms. Aerobic microbes such as Chlamydophila pneumoniae and Mycoplasma pneumoniae usually do not survive in oxidative stress media. Archaea are anaerobic microbes with powerful anti-oxidative enzymes that allow detoxification of free radicals whose presence might favor the survival of aerobic microorganisms. We searched for archaeal organisms in vulnerable plaques, and possible associations with myxoid matrix, chlamydia, and mycoplasma bodies. METHODS: Twenty-nine tissue samples from 13 coronary artherectomies from large excentric ostial or bifurcational lesions were studied using optical and electron microscopy. Infectious agents compatible with archaea, chlamydia, and mycoplasma were semiquantified using electron micrographs and correlated with the amounts of fibromuscular tissue, myxoid matrix, and foam cells, as determined from semi-thin sections. Six of the cases were also submitted to polymerase chain reaction with archaeal primers. RESULTS: All 13 specimens showed archaeal-compatible structures and chlamydial and mycoplasmal bodies in at least 1 sample. There was a positive correlation between extent of the of myxoid matrix and archaeal bodies (r = 0.44, P = 0.02); between archaeal and mycoplasmal bodies (r = 0.41, P = 0.03), and between chlamydial bodies and foam cells (r = 0.42; P = 0.03). The PCR test was positive for archaeal DNA in 4 of the 6 fragments. DISCUSSION: DNA and forms suggestive of archaea are present in vulnerable plaques and may have a fundamental role in the proliferation of mycoplasma and chlamydia. This seems to be the first description of apparently pathogenic archaea in human internal organ lesions. PROPOSTA: Placas vulneráveis são caracterizadas por matriz mixomatosa, centro lipídico necrótico, espécies reativas de oxigênio e alto níveis de microorganismos. Micróbios aeróbicos como Chlamydophila pneumoniae e Mycoplasma pneumoniae usualmente não sobrevivem em meio de estresse oxidativo. Arquéias são microorganismos anaeróbicos com poderosas enzimas anti-oxidantes que permitem detoxificação de radicais livres e a presença delas poderia favorecer a sobrevivência de micróbios aeróbicos. Pesquisamos por elementos de arquéia em placas vulneráveis e sua possível associação com degeneração mixomatosa da matriz e aumento do número de clamídias e micoplasmas. MÉTODOS: Vinte e nove amostras de 13 produtos de aterotomia de lesões grandes e excêntricas de óstio ou bifurcação de coronárias foram estudadas pela microscopia óptica e eletrônica. Agentes compatíveis com arquéia, clamídia e micoplasma foram semiquantificados pela microscopia eletrônica e correlacionados com quantidade de tecido fibromuscular, matriz mixomatosa e células xantomatosas. Seis casos foram também submetidos à reação em cadeia da polimerase com oligonucleotídeos de arquéia. RESULTADOS: Os 13 casos foram positivos para estruturas sugestivas de arquéia, micoplasma ou clamídia, em pelo menos uma amostra. Houve correlação positiva entre intensidade de matriz mixomatosa versus arquéia (r=0.44, p=0.02); arquéia versus micoplasma (r=0.41, p=0.03) e clamídia versus células xantomatosas r=0,42; 0.03). PCR foi positiva para DNA de arqueia em 4 dos 6 fragmentos. DISCUSSÃO: DNA e formas compatíveis com arquéia estão presentes em placas vulneráveis e podem ter papel fundamental na proliferação de micoplasma e clamídia. Este parece ser o primeiro relato de arquéia aparentemente patogênica em lesões de órgãos internos humanos.

Morphometric data obtained from the analysis of endomyocardial biopsy might be useful to evaluate prognosis of patients with dilated cardiomyopathy. We measured the myocyte diameter, its coefficient of variation and the fractional area of collagen in right ventricular endomyocardial biopsies of 35 outpatients with idiopathic dilated cardiomyopathy. None of the evaluated histological parameter was associated with the survival time of the patients (range: 2 to 5588; median: 706 days). Right ventricular endomyocardial biopsy should not be indicated to predict evolution or fatal outcome in patients with idiopathic dilated cardiomyopathy.

Advanced complicated atherosclerotic lesions have been related to many factors, including inflammation, infectious agents, and growth factors. Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP), inflammation, and growth factors have been associated with severe atherosclerotic lesions in necropsy material in recent work at our lab. The present study intends to clarify the pathogenesis of atherosclerosis, analyzing which of these elements (macrophages, MP, CP, lymphocytes, and growth factors) are associated with initial development of atherosclerotic lesions, discriminating elements related to stabilization of the plaque versus those related to subendothelial active accumulation of macrophages in living patients. Surgical ascending aorta fragments presenting mild atherosclerotic lesions from 30 coronary atherosclerotic patients were immunohistochemically quantified regarding CP, MP, T cells (CD4, CD8), B cells (CD20), macrophages (CD68), and growth factors [platelet-derived growth factor A (PDGF-A), PDGF-B, transforming growth factor-beta (TGF-beta), granulocyte-macrophage colony-stimulating factor (GM-CSF)]. Cases were grouped according to the presence or not of active accumulation of macrophages at the subendothelium that indicates atheroma in development: group I (GI) fragments with4 CD68+ cells/x400 field, in normal distribution (mean 1.8 +/- 1) representing stable atherosclerotic mild lesion, and GII fragments presentingor=4 CD68+ cells/x400 field, in a non-normal distribution, mean (8.9 +/- 4.8, atheromas in progress), which was followed by increased number of lymphocytes. The median number in GI was significantly lower than that in GII: CD4 T (2.5 vs. 7.7), CD8 T (1.0 vs. 5.5), and CD20 B (1.5 vs. 5.5) cells/x400 field, p0.001. Percentage area positive for CP antigens was significantly lower in GI than in GII: 1.0 vs. 9.2, p0.001. There was a higher percentage area occupied by MP than CP in both GI and GII (7.8 vs. 13.8). There was no difference regarding mean number of growth factor-positive cells/x400 field: PDGF-A, 1.4 vs. 3.9; PDGF-B, 3.4 vs. 5.7; TGF-beta, 0.9 vs. 2.2; and GM-CSF, 2.0 vs. 2.2. Considering all cases, a positive correlation was seen between inflammatory cells and CP+ cells (r0.5 and p0.01). Growth factors did not correlate with inflammatory cells, CP, or MP and were usually seen in smooth muscle cell and fibrotic areas. Study of initial atherosclerotic lesions showed that MP is present in both kinds of lesion: stable and active subendothelial accumulation of macrophages. Stabilization was related to proportional increase of both infectious agents, which were also related to increased amount of PDGF-A and PDGF-B. Active macrophage accumulation lesions were related to higher elevation in CP concentration at subendothelial regions, in association with B cells, but not of MP and growth factors. MP and CP, inflammation, and growth factors, which were already described in severe atherosclerotic lesions in necropsy material, are also present in mild lesions in living patients, strongly favoring a pathogenetic role for these bacteria in the pathogenesis of atherosclerosis. Predominance of CP in relation to MP may favor progression of the plaque, which is associated with increased B-cell proliferation. PDGF-A and PDGF-B are associated with plaque stability, at least in arterial segments not prone for development of complicated lesions.

PURPOSE: To investigate the relationship between the vascular diameter and the extent and histologic characteristics of atherosclerosis in the thoracic and abdominal aortas of patients who died of atherosclerotic disease. METHOD: We measured the vascular diameter and evaluated the percentage atrophy of the medial layer of the thoracic and abdominal aortas of 19 patients who died due to atherosclerotic disease. The extent of plaques, calcification, ulceration, thrombosis, and the amount of fat in the plaques were evaluated semiquantitatively. RESULTS: Atherosclerosis was more severe in the abdominal than the thoracic aorta as indicated by the higher sum of the macroscopic scores (P = .02) and the higher percentage atrophy of the medial layer (P < .001). The diameter of the thoracic, but not of the abdominal aorta, correlated with age (r = 0.56; P = .01), plaque score (r = 0.59; P = .008), calcification score (r = 0.749; P < .001), and fat score (r = 0.48; P = .04). Multiple linear regression showed that age (P = .06) and calcification score (P = .001) were the parameters with the strongest association to thoracic aorta diameter. CONCLUSION: There are some differences regarding atherosclerosis in the thoracic compared to the abdominal aorta. Progressive thoracic aorta atherosclerosis is associated with fat deposition in the plaques, inducing arterial dilation. In the abdominal aorta, atherosclerosis can either have a similar evolution or be associated with less fat deposition in the arterial wall, which would result in more rigidity, hindering compensatory arterial enlargement. OBJETIVO: Estabelecer relações entre o diâmetro vascular e a intensidade e características histológicas da aterosclerose, nos segmentos torácico e abdominal da aorta. MÉTODO: Foi medido o diâmetro vascular e avaliada a porcentagem de atrofia da camada média da aorta torácica e abdominal de 19 pacientes que faleceram devido a doença aterosclerótica. A presença de placas, calcificação, ulceração, trombose e a quantidade de gordura das placas foi avaliada, semiquantitativamente, nas mesmas regiões. RESULTADOS: A aterosclerose foi mais intensa na aorta abdominal que na torácica, conforme demonstrado pela maior soma dos escores macroscópicos (p = 0,02) e pela maior porcentagem de atrofia da camada média (p < 0,001). O diâmetro da aorta torácica, porém não o da abdominal apresentou correlação positiva com a idade (r = 0,56; p = 0,01), escore de placa (r = 0,59; p = 0,008), escore de calcificação (r = 0,749; p < 0,001) e escore de gordura (r = 0,48; p = 0,04). O modelo de regressão linear múltipla evidenciou que as variáveis mais associadas ao diâmetro da aorta torácica foram a idade (p = 0,06) e o escore de calcificação (p = 0,001). CONCLUSÃO: A aterosclerose apresenta algumas características distintas nos segmentos torácico e abdominal da aorta. A progressão da aterosclerose na aorta torácica associa-se à deposição de gordura nas placas, ocorrendo dilatação arterial. Na aorta abdominal a aterosclerose pode apresentar evolução semelhante ou estar relacionada à menor deposição de gordura na parede arterial, que se tornaria mais rígida, impedindo a dilatação compensatória.

We investigated whether Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP) are present in aortic valve stenosis (AS).Immunohistochemistry was utilized to identify CP antigens, in situ hybridization to identify MP DNA, and electron microscopy was used to evaluate the following three groups: Normal - 11 normal autopsy valves; Atherosclerosis - 10 autopsy valves from patients with systemic atherosclerosis and no AS; and AS - 14 surgical specimens of AS analyzed in 3 sub-regions: AS-Preserved - peripheral, preserved regions; AS-Fibrosis - peri-calcified fibrotic tissue; and AS-Calcification - calcified nodules.The positive area fraction of CP antigen median values were 0.09, 0.30, 0.18, 1.33, and 3.3 in groups Normal, Atherosclerosis, AS-Preserved, AS-Fibrosis, and AS-Calcification, respectively. CP density was significantly greater in Atherosclerosis and AS-Calcification than in Normal (P0.05). Within the AS group, the amount of CP was greater in the Calcification and Fibrosis regions (P0.05). MP-DNA positive area fraction (median values) were 0.12, 0.44, 0.07, 0.36, and 1.52 in groups Normal, Atherosclerosis, AS-Preserved, AS-Fibrosis, and AS-Calcification, respectively. The amount of MP-DNA was greater in AS-Calcification than in Normal (P0.05). Within the AS group, MP-DNA was in larger quantity in the Calcification and Fibrosis regions (P0.05).AS Calcified nodes present higher concentration of CP and MP suggesting that these bacteria may be associated with the development of calcification and inflammation. This adds novel similarities between AS and the atherosclerosis process, which may have infection mechanisms involved.

OBJETIVO: Investigar se chlamydia pneumoniae (CP) ou mycoplasma pneumoniae (MP) estão presentes na estenose da valva aórtica (EA). MÉTODOS: Imuno-histoquímica foi utilizada para identificar os antígenos de CP (Ag-CP), a hibridização in situ para identificar o DNA de MP, e microscopia eletrônica para avaliação dos dois agentes, nos grupos: normal - 11 valvas normais de autópsia; aterosclerose - 10 valvas de pacientes com aterosclerose sistêmica de autópsia e sem EA; e EA - 14 espécimes cirúrgicos provenientes de pacientes com EA analisados em 3 sub-regiões: EA-preservada - regiões mais preservadas na periferia da valva; EA-fibrose - tecido fibrótico peri-calcificação; e EA-calcificação - nódulos calcificados. RESULTADOS: As medianas da fração de área positiva para Ag-CP foram 0,09; 0,30; 0,18; 1,33; e 3,3 nos grupos acima descritos, respectivamente. A densidade de CP foi significativamente maior nos grupos aterosclerose e EA-calcificação em relação ao normal (p

Polymerase chain reaction (PCR) has been used to detect microbiological agent recurrence after heart transplantation of viral-induced cardiomyopathies. We report a case of reactivation of Chagas' disease after heart transplantation in which parasites could be detected in the endomyocardial biopsy using hematoxylin-eosin-stained sections, immunohistochemistry, and PCR for Trypanosoma cruzi DNA. Interestingly, PCR results remained positive in the endomyocardial biopsy 53 days after the beginning of successful treatment, pointing to the possibility of chronic persistence of parasites in the myocardium after the reactivation of Chagas' disease.

A lower incidence of acute myocardial infarction was reported in patients with chronic liver disease.To analyze the impact of chronic liver disease on characteristics associated with vulnerability of human coronary artery atherosclerotic plaques.One hundred fourteen hearts were collected from 3 groups of individuals: A--38 chronic liver disease patients who died while on the waiting list for liver transplantation; B--38 individuals who died of natural causes; and C--38 individuals who died of accidental causes. The most obstructed portion of the initial 2-cm segment of coronary arteries was histologically evaluated regarding to plaque area, luminal area, inflammation, percentage of fat, and total vessel area.The mean age (years) and male frequency in groups A, B and C were, respectively, 52+/-9 and 79%; 52+/-11 and 71%; and 54+/-18 and 89%. The mean area of the plaque and the incidence of severe plaque inflammation in group A were significantly lower (4.2+/-3.2; 13.2%) than those in the other two groups (6.6+/-4.3; 84.2%, and 6.3+/-4.4; 52.6%) p0.01. The cross-sectional vessel measures were not statistically different regarding to vessel area (10.5+/-4.6; 12.1+/-4.6; 13.0+/-4.4) p=0.08, luminal obstruction (45%+/-15%; 60%+/-20%; 53%+/-20%) p=0.07, and fat area in the plaque (16%+/-17%; 30%+/-24%; 18%+/-18) p=0.37. In conclusion, compared with the general population, chronic liver disease patients have coronary arteries with smaller intimal plaque and less vessel inflammation. These findings favor the concept that hepatic disease patients are less prone to develop complicated coronary atherosclerosis.

In this review we report recent findings of our lab showing that Mycoplasma pneumoniae and Chlamydia pneumoniae are present in higher amount, associated with adventitial inflammation and positive vessel remodeling, in thrombosed coronary artery segments (CAS) of patients who died due to acute myocardial infarction. CD8T cell was the predominant lymphocytes in the plaque and CD24(B) cell in the adventitia. The mean numbers of lymphocytes were significantly higher in adventitia than in the plaque. Vulnerable plaques were usually associated with focal positive vessel remodeling and large lipidic atheromas. Mycoplasma is the only bacterium that needs cholesterol for proliferation. We hypothesized that the association of Mycoplasma pneumoniae and Chlamydia pneumoniae increases virulence of both bacteria, inducing inflammation and rupture of the plaque. The search of CMV and Helicobacter pylori resulted negative.

Background The process of aortic degeneration associated with calcified aortic stenosis shares many similarities with coronary artery atherosclerosis. Inflammation and infection are involved in both diseases. Chlamydia pneumoniae has been identified in atherosclerotic plaques. However, the studies about the presence of C. pneumoniae in degenerative aortic stenotic valves are not conclusive. Objective We investigated whether an association exists between the density of C. pneumoniae and fibrosis or calcification in aortic stenosis. Design Autopsy and surgical specimens were divided into 3 groups: Normal, 11 normal autopsy valves Atherosclerosis, 10 autopsy valves from patients with systemic atherosclerosis and no aortic stenosis and Aortic stenosis, 14 surgical specimens of aortic valves replaced due to aortic stenosis. Setting Heart Institute (InCor), University of Sao Paulo Medical School. Patients Aortic valves from patients aged 52±16 years, 69±9 years, and 71±8 years. Invention Specimens were evaluated by immunohistochemical technique (to detect C. pneumoniae antigens), in situ hybridization, and electron microscopy (to quantify the density of C. pneumoniae in the valves). Measurements The aortic stenosis group was analyzed according to 3 subregions: aortic stenosis-preserved, peripheral preserved regions; aortic stenosis-fibrosis, peri-calcified fibrotic tissue; and aortic stenosis-calcification, calcified nodules. Results The median values of C. pneumoniae antigens were 0.09, 0.30, 0.18, 1.33, and 3.3 in groups Normal, Atherosclerosis, Aortic stenosis-preserved, Aortic stenosis-fibrosis, and Aortic stenosis-calcification, respectively. The amount of C. pneumoniae was greater in the Atherosclerosis and Aortic stenosis-calcification groups than in the Normal group ( P C. pneumoniae was greater in the Aortic stenosis group in the calcified and fibrotic regions than in preserved region ( P Conclusion An association was found between the higher density of C. pneumoniae and fibrosis/calcification in stenotic aortic valves.

Deposits of myxoid material, similar to myxedema related to thyroid disease, are described in the medial layer of aortas with dissection. We analyzed the clinical or subclinical thyroid dysfunction of patients with this disease and analyzed whether a correlation exists between serum levels of thyroid-related hormones and the myxoid content of the aortic media.We measured, with standard methods, serum levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) in 28 patients who underwent aortic dissection and free T4 in 20 of them. The same hormones were quantified in 20 control patients matched by sex and age. Results were compared by using the Mann-Whitney test. We also measured the percentage of the aortic media occupied by myxoid material in the surgical specimens of 25 of the patients with aortic dissection and analyzed its correlation with hormone levels by using the Pearson test.In the 20 pairs in which the amount of hormones was compared, the mean values for T3, T4, free T4, and TSH were 1.22ng/mL, 9.89mcg/dL, 1.18ng/dL, and 5.45 microIU/mL in study patients and 1.15ng/mL, 8.57mcg/dL, 1.32ng/dL, and 2.15 microIU/mL in controls. Neither these differences nor the correlation between the percentage of myxoid content (mean=30%) and the values for T3, T4, free T4, and TSH (mean 1.22ng/mL, 9.44mcg/dL, 1.20ng/dL, and 5.08 microIU/mL, respectively; n= 25) were significant.Our data suggest that serum levels of thyroid hormones have no relation with the myxoid content in the aortic media in cases of aortic dissection.

The present paper proposes a new therapy using Trypanosoma cruzi trans-sialidase to treat diseases with unclear pathogenesis that present in common chronic inflammation and fibrosis. This hypothesis is based on recent findings that co-infection with mycoplasma and chlamydia is present in many of these diseases and that this enzyme was capable to eliminate or decrease the co-infection from the host. We identified that mycoplasmas and chlamydias are present in atherosclerosis, aortic valve stenosis, dilated cardiomyopathy, chronic chagasic myocarditis and cancer. We hypothetized that mycoplasmal infection may induce immunodepression in the host, favoring proliferation of pre-existent chlamydial infection and that elimination of mycoplasma would lead to improvement of the immune system resistance and the control of chlamydial proliferation. Mycoplasma has a particular parasitic relationship with host cells, involving strong adherence of their membranes, making it extremely difficult to eradicate mycoplasmal infection from the host. A new therapeutic approach is suggested using one or more agents that prevent or inhibit the adherence of mycoplasma to host cell membranes by removing sialic acid residues and preventing oxidation of the cells. The use of a neuraminidase enzyme, particularly the T. cruzi trans-sialidase enzyme, associated with treatment using anti-oxidating agents is proposed. Preliminary experimental animal and laboratory tests showed good results. The proposal that trans-sialidase from T. cruzi is efficient in combating co-infection of mycoplasma and chlamydia is based, at least in part, on the observation that chagasic patients suffering from T. cruzi infection present less mycoplasma and chlamydia infection in their tissues. Also, a lower incidence of the diseases above described to be related to mycoplasma infection is observed in chagasic patients. It is also hypothesized that co-infection with mycoplasma and chlamydia may induce oxidation of the host cells. Anti-oxidants such as those present in plant extracts may also be used in the treatment. Other diseases such as chronic hepatitis, glomerulonephritis, Multiple Sclerosis, Alzheimer's Syndrome and idiopathic encephalitis are other examples of chronic diseases where mycoplasma and chlamydia might be present, as they have the characteristics of unknown etiology, persistent chronic inflammation and fibrosis.

OBJETIVO: Pesquisar a ocorrência de disfunção clínica ou subclínica da tireóide em portadores de dissecção aórtica e analisar se há correlação entre os níveis séricos de hormônios relacionados à função tireoideana e ao conteúdo de material mixóide da média aórtica. MÉTODOS: Níveis séricos de triiodotironina (T3), tiroxina (T4) e hormônio estimulador da tireóide (TSH) foram dosados por métodos convencionais em 28 pacientes em pós-operatório de correção de dissecção aórtica; T4 livre foi medido em 20 deles. Os mesmos hormônios foram quantificados em 20 pacientes-controle pareados por sexo e idade. Os resultados foram comparados pelo teste de Mann-Whitney. A porcentagem da camada média da aorta ocupada por material mixóide foi medida em espécimes cirúrgicos de 25 pacientes e correlacionada aos níveis séricos de hormônios através do teste de Pearson. Estabeleceu-se o nível de significância como p

A 61 year-old Chagasic woman, with previous left ventricular systolic disfunction, ventricular tachychardia and cardiac pacemaker, presented cardiac arrest in asystolia after surgical ressection of apical aneurysm.

A 61 year-old Chagasic woman, with previous left ventricular systolic disfunction, ventricular tachychardia and cardiac pacemaker, presented cardiac arrest in asystolia after surgical ressection of apical aneurysm.

OBJECTIVE: To study atheromas, Mycoplasma pneumoniae (M. pneumoniae), and Chlamydia pneumoniae (C. pneumoniae). METHODS: C. pneumoniae was studied with immunohistochemistry and M. pneumoniae with in situ hybridization (ISH), in segments of coronary arteries (SCA) as follows: group A - thrombosed ruptured plaques (TRP) of 23 patients who died due to acute myocardial infarction (AMI); group B - 23 nonruptured plaques (NRP) of group A patients; group C - NRP of 11 coronary patients who did not die due to AMI; and group D - 11 SCA from patients with dilated cardiomyopathy or Chagas' disease without atherosclerosis. RESULTS: The mean number of C. pneumoniae+ cells/400x in groups A, B, C, and D was, respectively, 3.3±3.6; 1.0±1.3; 1.2±2.4; and 0.4±0.3; and the percentage of M. pneumoniae area was, respectively, 3.9±3.5; 1.5± 1.6; 0.9±0.9; and 0.4±0.2. More M. pneumoniae and C. pneumoniae were found in of group A than in group B (P

Routine examinations of conventional outbred Wistar rats in our laboratory showed increased serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and urea. Electron microscopy and specific reactions showed C. pneumoniae and M. pulmonis in lung, liver, spleen, heart, and kidney sections. We could not exclude the fact that other infectious microorganisms detected through routine health surveillance affected the Wistar rat colony; however, we have not identified any of those microorganisms by electron microscopy of the organs listed. Natural coinfection of C. pneumoniae and M. pulmonis can occur in laboratory rats and is associated with histopathological and functional compromise of many organs. Further studies comparing different conventional animals and specific pathogen-free animals are necessary to better understand the present findings and to define whether coinfection influences the results of experimental studies with rats.

The membrane attack complex (MAC) of complement participates in several inflammatory and proliferative processes by releasing pro-inflammatory cytokines and growth factors from target cells. Chronic Chagasic cardiomyopathy (CCH) is a parasitic dilated cardiopathy, characterized by severe fibrosis and inflammation, which differs from idiopathic dilated cardiomyopathy (DCM). Trypanosoma cruzi, the pathogenic organism of CCH, is a strong complement activator and can also induce alternative pathway activation by mammalian cells. This study explored whether the myocardium in CCH patients has increased MAC deposition, an expression of complement activation, compared to DCM patients. MAC was semi-quantified in endomyocardial human samples (29 CCH subjects, 18 DCM subjects, and four controls) by immunohistochemistry. MAC was present in the sarcolemma of 38% of CCH, 5.5% of DCM (p

This case report describes the electrophysiological findings of a 62-year-old patient with chronic Chagas' disease and two distinct morphologies of sustained ventricular tachycardia that involved a mitral isthmus. Multiple RF applications were necessary to obtain a bidirectional conduction block in the mitral isthmus that was related to the interruption of both tachycardias. After the procedure, the patient presented massive cerebral infarction that progressed to coma and death. Autopsy showed acute and old lesions at the mitral isthmus and recent mitral annulus thrombosis.

Several lines of clinical evidence show that AMI frequently occurs at sites with mild to moderate degree of coronary stenosis. The degree of luminal stenosis depends on plaque deposition and degree of vessel remodeling, features poorly assessed by coronary angiography. This postmortem study tested the hypothesis that the size of coronary atheroma and the type of remodeling distinguish culprit lesion responsible for fatal AMI from equi-stenotic nonculprit lesion in the same coronary tree. The main coronary branches from 36 consecutive patients with fatal AMI were studied. The culprit lesion (Group 1) and an equi-stenotic nonculprit segment (Group 2) obtained in measurements of another coronary branch from the same patient were compared. Morphometry and plaque composition was assessed in both groups. Compared to Group 2, Group 1 had larger areas of: plaque 9.6 vs. 4.7 mm(2), vessel 12.7 vs. 7.4 mm(2) and lumen 1.7 vs. 1.2 mm(2); (P.01). Positive remodeling was more frequent in Group 1 than Group 2: 21/30 (70%) vs. 8/26 (31%). Plaque area correlated positively with lipid core and macrophages and negatively with fibrosis and smooth muscle cells. Atherosclerotic plaques that cause fatal thrombosis are more frequently positively remodeled and tend to be larger than nonculprit plaques with the same degree of cross-sectional stenosis. We tested whether arterial remodeling and plaque size vary between segments containing a fatal thrombosed plaque versus an equi-stenotic nonculprit plaque. Culprit vessel segments had higher cross-sectional areas of intimal plaque and of vessel wall than equi-stenotic nonculprit plaques. The cross-sectional area of the vessel correlated positively with both the lipid core area and CD68(+) macrophage content, and negatively with fibrosis area and smooth muscle cell content. These results add elements explaining limitations of angiography in identifying plaques and provide new insights into the role of remodeling in plaque instability.

Patients submitted to dynamic cardiomyoplasty had an initial clinical improvement followed by a decrease in cardiac failure indices. A histopathological study of the skeletal muscle was undertaken to explain this. Latissimus dorsi fragments from 15 patients submitted to dynamic cardiomyoplasty in a 1:1 (heart beat:muscle stimulation) conditioning were analysed by light microscopy. The interval between surgery and obtaining the specimens (13 from necropsies, two from heart transplants) ranged from 37 days to 6 years. Nuclear clumps and internalization, the presence of round fibres, inflammation, and fibrosis were analysed semi-quantitatively; the thickness of muscle fibres and the percentage of tissue fat were measured by image analysis. The quantitative data were also compared, in 12 cases, with gender- and age-matched necropsy controls. The mean thickness of muscle fibres in cases and controls was 27.21+/-5.33 and 40.84+/-9.42 microm, respectively (p=0.001). The percentage of tissue fat in cases and controls was 12.04+/-12.66% and 0.93+/-0.91%, respectively (p=0.008). The duration of grafts correlated positively with the quantity of nuclear clumps (R=0.80, p

ObjectiveTo elucidate the histologic changes after stent graft oversizing in nonatherosclerotic aortas using an experimental porcine model. We previously reported that the diameter and angulation of the aorta in this model are similar to those in young individuals who undergo stent graft repair for blunt aortic injuries. The lack of commercially available stent grafts specific for repairing blunt aortic injuries, particularly for small and angulated aortas, may be related to the high rate of endograft complications in this population.MethodsTwenty-five pigs were randomized into one control group (without stent graft implantation) and four oversized groups (A: 10%-19%, B: 20%-29%, C: 30%-39%, and D: >40%). Three circumferential fragments were collected from the aorta for histologic and immunohistochemical studies. Morphometric analyzes were performed using an inflow system and image analysis software (Quantimet 500; Leica Cambridge Ltd, Cambridge, UK).ResultsCollagen expression in the aortic wall was not significantly different among the five groups (P = .5604). There were significantly fewer muscle fibers in the aortic wall in the oversized groups compared with the control group (P = .000198). The proportion of elastic fibers in the aortic wall was significantly smaller in the oversized groups compared with the control group (P = .0000001). Immunohistochemical analysis showed that α-actin expression in the aortic wall was significantly decreased in the oversized groups compared with the control group (P = .002031). There were no significant differences in either the number of muscle fibers or α-actin expression among the four oversized groups.ConclusionsHistologic and immunohistochemical studies confirmed the structural disarrangement of the aortic wall after insertion of an endoprosthesis, including reduced number of muscle and elastic fibers.Clinical RelevanceBlunt aortic injury is a catastrophic event that most commonly affects the descending thoracic aorta, and it is the second most common cause of death in trauma patients. Thoracic endovascular aortic repair is increasingly being used to treat such conditions. The prostheses available at the time we conducted the present study were not specifically designed to treat thoracic aortic trauma. Furthermore, few stent grafts had been designed for use in normal or healthy aortic tissue or in young patients with acute angulation of the thoracic aorta. To our knowledge, no large study has evaluated the optimal target level of oversizing in thoracic aortas, especially for nonatherosclerotic aortas. We have conducted an experimental study in which we evaluated the biomechanical changes associated with four levels of stent graft oversizing on a nonatherosclerotic aortic wall. In the present report, we describe the histologic and immunohistochemical results of that study.

Neste trabalho, quantificamos fatores de crescimento em fragmentos de miocárdio de 19 cardiopatas chagásicos crônicos com insuficiência cardíaca congestiva, através da técnica da imunoperoxidase. Pesquisamos: antígenos de T. cruzi , fatores de crescimento (GM-CSF, TGF-beta1, PDGF-A e PDGF-B) e células inflamatórias (CD4+, CD8+, CD20+ e CD68+). A razão média CD4+/CD8+ foi 0,6 ± 0,3. O número médio de macrófagos (CD68+) foi 5,9±3,1; de células intersticiais PDGF-A+ foi 7,5 ± 4,3; PDGF-B+ 2,9 ± 2,7, TGF-beta1+ 2,2 ± 1,9 e GM-CSF+ 2,3 ± 1,9. A marcação para PDGF-A foi geralmente intensa, ocorrendo também em endotélio, células musculares lisas e sarcolema; não houve correlação dessa positividade com a quantidade de células intersticiais positivas para os mesmos fatores. TGF-beta1 ocorreu em baixa expressão em 100% dos casos. Em conclusão, PDGF-A e B são, provavelmente, os fatores de crescimento mais relacionados às lesões proliferativas na cardiopatia chagásica crônica e, conseqüentemente, à fibrose. GM-CSF e TGF-beta1 estão pouco expressos. Não houve correlação estatisticamente significante entre os fatores de crescimento e a quantidade de parasita. In this work we quantified various growth factors in the myocardium of 19 patients with chronic chagasic cardiomyopathy and heart failure, through the immunoperoxidase technique. We looked for T. cruzi antigens, growth factors (GM-CSF, TGF-beta1, PDGF-A and PDGF-B) and inflammatory cells (CD4+, CD8+, CD20+ and CD68+). The mean ratio of CD4+/CD8+ T lymphocytes was 0.6 ± 0.3. The mean number of positive interstitial cells was 5.9 ± 3.1 for CD68+ (macrophages); 7.5 ± 4.3 for PDGF-A+; 2.9 ± 2.7 for PDGF-B+, 2.2 ± 1.9 for TGF-beta1+ and 2.3 ± 1.9 for GM-CSF+. The immunoreaction for PDGF-A was intense, occurring also in the endothelium, smooth muscle cells and the sarcolemma; there was no correlation between the number of positive interstitial cells and the semiquantitation of the same growth factors in the other cells. TGF-beta1 presented low expression in 100% of the cases. In conclusion, PDGF-A and B are probably the growth factors most related to the proliferative lesions and fibrosis present in chronic chagasic cardiomyopathy. GM-CSF and TGF-beta1 are present in low levels. There was no statistical correlation between growth factors and the quantity of the parasitic antigens.

A possible relationship between C.pneumoniae (CP) infection, atherosclerosis and acute myocardial infarction is a debated matter. Now we performed the search of CP in histological segments of fatal ruptured plaques and of stable plaques by histochemistry (Macchiavello stain), immunohistochemistry and in situ hybridization techniques. Electron microscopy and confocal laser microscopy techniques were used in two additional cases. The semi-quantitification of CP + cells (0-4+) and quantification of lymphocytes demonstrated greater amount of CP + cells and more inflammation in the adventitia of vulnerable plaque vessel segments than of stable ones, larger amount of CP + cells in adventitia than in the plaque and high frequency of CP + cells in all groups studied. This preliminary study strongly suggests a direct pathogenetic involvement of adventitial CP in the rupture of the atheromatous plaque, development of acute myocardial infarction and also in the development of atherosclerosis.

Partial left ventriculectomy has been proposed for treatment of severe cardiomyopathies. This study reports midterm results of this procedure in 37 patients with dilated cardiomyopathy.All patients were in New York Heart Association class III (16) or IV (21). Partial ventriculectomy was associated with mitral annuloplasty in 27 patients and with mitral replacement in 2.There were seven operative deaths (18.9%). During a mean follow-up of 18.2+/-9.3 months, 9 more patients died. Actuarial survival was 56.7%+/-8.1% at 6 and 24 months. Analysis of factors influencing outcome showed that midterm survival was significantly affected only by myocardial cell diameter. Otherwise, functional class improved from 3.5+/-0.5 to 1.8+/-0.9 in the survivors (p0.001). Furthermore, left ventricular diastolic volume decreased from 523+/-207 to 380+/-148 mL (p0.001), and left ventricular ejection fraction increased from 17.1%+/-4.6% to 23%+/-8% (p0.001), whereas significant changes in cardiac index, stroke index, and pulmonary pressures were found at 1 month of follow-up. Although left ventricular diastolic volume tended to increase in the late postoperative period, left ventricular ejection fraction and hemodynamic variables did not change significantly.Partial ventriculectomy improves left ventricular function and congestive heart failure in patients with dilated cardiomyopathy for up to 24 months of follow-up. Nevertheless, this procedure's clinical application is limited by the high mortality observed in the first postoperative months. Otherwise, new perspectives may be advised by the identification that partial ventriculectomy results seem to be influenced by compromised myocardial cells.

Aortic dissections (AD) are characterized by the separation of the artery into two sheets, possibly due to fragility of the vessel wall. A mucoid histological pattern, imparted to the tissues mainly by hyaluronan and proteoglycans, can be seen in "cysts" and, in chronic cases, in a band of repair tissue. We studied the localization of hyaluronan, versican, decorin and biglycan in situ in aortas of 21 patients with recent AD, 8 with chronic AD and in 15 control cases. None of these substances was increased in the areas of mucoid "cysts" that possibly contain anomalous material. Similar distributions were seen in normal and dissected aortas: versican and hyaluronan were more prominent in the external half of the medial layer where the dissection usually occurs. Since these molecules play a role in resistance to compression, disorders not detected by our method may be involved in aortic dissection. Hyaluronan was seen adjacent to fibrin at the dissection tear, probably as an early wound repair phenomenon. Biglycan, hyaluronan and mostly versican are seen during advanced repairing. The mucoid deposits may represent various compounds which reflect different disorders in vascular biology.

Summary Expression and distribution of atrial natriuretic peptide (ANP) were studied immunohistochemically in the conducting system and internodal atrial myocardium of 5 adult human hearts. Myocytes from the sinus node and compact atrioventricular node were usually ANP-negative; only a very few cells exhibited ANP immunoreactivity. These ANP-positive myocytes were small and did not appear to be trapped working atrial myocytes which are larger than nodal cells. The transitional cell zones of the sinus node and the atrioventricular node were composed of bundles of ANPpositive myocytes, intermingled with non-reactive myocytes. The internodal atrial myocardium exhibited a comparable intensity of myocyte staining in each case examined. Thus, morphologically distinct connecting pathways between the sinus node and the atrioventricular node with regard to myocyte ANP immunoreactivity could not be demonstrated, reinforcing the notion that they actually do not exist. The penetrating bundle, branching bundle and bundle branches were usually composed of ANP-negative myocytes although some ANP-positive myocytes were observed in the branching bundle and bundle branches in 4 cases. Myocytes from the ventricular conducting tissue presenting ANP immunoreactivity have been designated Purkinje fibers and have been found in several mammalian species.

Inflammatory cells positive for the cytokines IL-2, IL-4, IL-6, TNF-alpha, and IFN-gamma and for IL-2R, as well as CD8+ and CD4+ T cells and B cells were quantified using an immunoperoxidase technique in 25 fresh myocardial fragments from patients presenting with chronic chagasic cardiomyopathy. The presence of Trypanosoma cruzi antigens (Ags) in the myocardium was also investigated. The cases were grouped into group A (no Ag), group B (scarce extramyocardial fiber Ags), and group C (intramyocardial pseudocysts and extramyocardial fiber Ags). IL-2 was detected in very few cells (0.30 +/- 0.40 positive cells/hpf), suggesting immunological imbalance in chronic chagasic patients. IFN-gamma+ was the cytokine most frequently demonstrated (7.52 +/- 5.87 positive cells/hpf) and there was a good correlation between the number of IFN-gamma+ cells and CD8+ T cells in group A. IL-4+ cells were present in higher numbers in group C (2.78 +/- 1.49 positive cells/hpf). TNF-alpha+ (1.59 +/- 1.68 positive cells/hpf) and IL-6+ (2.76 +/- 2.32 positive cells/hpf) cells were present in moderate numbers. Fewer B cells were present, not related with the intensity of T. cruzi Ags. These results suggest that cytokines, as they occur in other infectious diseases, play a fundamental role in the control of T. cruzi in chronic human chagasic disease. A fatal outcome seems to be associated with the increased production of cytokines derived from the Th2 subpopulation of the CD4+ T cells.

Chagas' disease has been considered a contraindication to heart transplantation as Trypanosoma cruzi infection could recur after immunosuppression.We report the follow-up of 22 patients who underwent orthotopic heart transplantation for treatment of end-stage chronic Chagas' heart disease, divided in two groups. Group 1 consisted of 9 patients operated on from September 1985 to June 1991, and group 2 patients underwent transplantation from July 1991 to June 1995. After our early experience with group 1, we attempted to use a lower cyclosporine dosage in group 2.Total actuarial survival at 24 months was 60%, and it was better for group 2 (33% for group 1, 80% for group 2, p = 0.008). Parasitemia occurred similarly in both groups, but Chagas' disease reactivation was seen in 5 group 1 patients and in 1 group 2 member (p0.002). Neoplasia developed in 5 group 1 patients and 1 group 2 patient, and contributed to death in 3 of them.These data demonstrate satisfactory outcome of cardiac transplantation in patients with end-stage Chagas' heart disease in the second phase of our experience. Further progress is necessary to improve the results and evaluate its proper role in the management of this disease.