This review focuses on the short and bewildered history of Brazilian scientist Carlos Chagas's discovery and subsequent developments, the anatomopathological features of chronic Chagas cardiomyopathy (CCC), an overview on the controversies surrounding theories concerning its pathogenesis, and studies that support the microvascular hypothesis to further explain the pathological features and clinical course of CCC. It is our belief that knowledge of this particular and remarkable cardiomyopathy will shed light not only on the microvascular involvement of its pathogenesis, but also on the pathogenetic processes of other cardiomyopathies, which will hopefully provide a better understanding of the various changes that may lead to an end-stage heart disease with similar features. This review is written to celebrate the 100th anniversary of the discovery of Chagas disease.

Evidence from our laboratory has shown alterations in myocardial structure in severe sepsis/septic shock. The morphological alterations are heralded by sarcolemmal damage, characterized by increased plasma membrane permeability caused by oxidative damage to lipids and proteins. The critical importance of the dystrophin-glycoprotein complex (DGC) in maintaining sarcolemmal stability led us to hypothesize that loss of dystrophin and associated glycoproteins could be involved in early increased sarcolemmal permeability in experimentally induced septic cardiomyopathy. Male C57Bl/6 mice were subjected to sham operation and moderate (MSI) or severe (SSI) septic injury induced by cecal ligation and puncture (CLP). Using western blot and immunofluorescence, a downregulation of dystrophin and b-dystroglycan expression in both severe and moderate injury could be observed in septic hearts. The immunofluorescent and protein amount expressions of laminin-a2 were similar in SSI and sham-operated hearts. Consonantly, the evaluation of plasma membrane permeability by intracellular albumin staining provided evidence of severe injury of the sarcolemma in SSI hearts, whereas antioxidant treatment significantly attenuated the loss of sarcolemmal dystrophin expression and the increased membrane permeability. This study offers novel and mechanistic data to clarify subcellular events in the pathogenesis of cardiac dysfunction in severe sepsis. The main finding was that severe sepsis leads to a marked reduction in membrane localization of dystrophin and b-dystroglycan in septic cardiomyocytes, a process that may constitute a structural basis of sepsis-induced cardiac depression. In addition, increased sarcolemmal permeability suggests functional impairment of the DGC complex in cardiac myofibers. In vivo observation that antioxidant treatment significantly abrogated the loss of dystrophin expression and plasma membrane increased permeability supports the hypothesis that oxidative damage may mediate the loss of dystrophin and b-dystroglycan in septic mice. These abnormal parameters emerge as therapeutic targets and their modulation may provide beneficial effects on future cardiovascular outcomes and mortality in sepsis. KEYWORDS: sepsis; septic cardiomyopathy; dystrophin; b-dystroglycan; dystrophin-glycoprotein complex (DGC); myocardial dysfunction; sarcolemmal permeabilityThe dystrophin-glycoprotein complex (DGC), which is located in the sarcolemma of cardiac and skeletal muscle cells and concentrated along the plasma membrane in costameric structures that correspond to the Z bands of the sarcomeres, provides a framework that connects the intracellular cytoskeleton to the extracellular matrix, transmits force between the sarcomere and the plasma membrane to the extracellular matrix and confers structural stability to the cell membrane. 1Deficiency of dystrophin results in Duchenne muscular dystrophy (DMD) as well as an associated cardiomyopathy in human patients. The mdx mouse, which lacks dystrophin because of a spontaneous mutation o...

No abstract

Hypertension causes cardiac hypertrophy, one of the most important risk factors for heart failure (HF). Despite the importance of cardiac hypertrophy as a risk factor for the development of HF, not all hypertrophied hearts will ultimately fail. Alterations of cytoskeletal and sarcolemma-associated proteins are considered markers cardiac remodeling during HF. Dystrophin provides mechanical stability to the plasma membrane through its interactions with the actin cytoskeleton and, indirectly, to extracellular matrix proteins. This study was undertaken to evaluate dystrophin and calpain-1 in the transition from compensated cardiac hypertrophy to HF. Wistar rats were subjected to abdominal aorta constriction and killed at 30, 60 and 90 days post surgery (dps). Cardiac function and blood pressure were evaluated. The hearts were collected and Western blotting and immunofluorescence performed for dystrophin, calpain-1, alpha-fodrin and calpastatin. Statistical analyses were performed and considered significant when p<0.05. After 90 dps, 70% of the animals showed hypertrophic hearts (HH) and 30% hypertrophic+dilated hearts (HD). Systolic and diastolic functions were preserved at 30 and 60 dps, however, decreased in the HD group. Blood pressure, cardiomyocyte diameter and collagen content were increased at all time points. Dystrophin expression was lightly increased at 30 and 60 dps and HH group. HD group showed decreased expression of dystrophin and calpastatin and increased expression of calpain-1 and alpha-fodrin fragments. The first signals of dystrophin reduction were observed as early as 60 dps. In conclusion, some hearts present a distinct molecular pattern at an early stage of the disease; this pattern could provide an opportunity to identify these failure-prone hearts during the development of the cardiac disease. We showed that decreased expression of dystrophin and increased expression of calpains are coincident and could work as possible therapeutic targets to prevent heart failure as a consequence of cardiac hypertrophy.

Introduction In 2002, the Surviving Sepsis Campaign defi ned a strategy that aimed to reduce the high mortality due to sepsis. One point of this strategy was a recommendation to recognize that sepsis is a frequent cause of death and high economic costs in the pediatric intensive care unit. Knowledge of the disease is the fi rst step to impact it. There are few studies on pediatric sepsis epidemiology in the world and none in Colombia. Hypothesis The epidemiological features of Colombian children are diff erent from other countries. Methods We constructed a website where 14 intensive care units across the country reported in a prospective way the epidemiological features of children with sepsis using an electronic process [1]. We asked for sociodemographics, microbiological data, sepsis classifi cation, complications, and outcome. Results We collected 253 patients from March to May 2009. Fifty-fi ve percent of the cases were male and 45% were female; 53% were less than 1 year old. A total of 67.2% came from urban areas and 33% came from rural villages. Eighty-fi ve percent were very poor (score 1 and 2 over 6 used in Colombia as socioeconomic classifi cation). Forty-fi ve percent have governmentsupported insurance. In total, 23.72% of the population presented with sepsis; 30.04% with severe sepsis; and 46.5% with septic shock. The infection origin was respiratory in 54.55%, followed by abdominal in 17.39%. In 50.2% no cause was identifi ed. A total of 75.1% required mechanical ventilation. The mortality rate was 20.4%. Conclusions Sepsis, severe sepsis, or septic shock is a common diagnosis in Colombian intensive care units. The majority of pediatric patients are 2 years or younger and from the poorest communities. It aff ected males more. In the majority, the process starts in the respiratory system. We had diffi culty identifying the cause. The disease causes high mortality and cost for a developing society. We need a complete survey to fi nd a correct approach to the problem. Reference 1. Sepsis en Columbia [www.sepsisencolombia.com] P2 Randomized controlled trials are not designed to prove the safety of third-generation hydroxyethyl starch for resuscitation: results from a systematic review