Analysis of Three-Dimensional Scar Architecture and Conducting Channels by High-Resolution Contrast-Enhanced Cardiac Magnetic Resonance Imaging in Chagas Heart Disease

We aimed to describe the morphology of the border zone of viable myocardium surrounded by scarring in patients with Chagas heart disease and study their association with clinical events.Adult patients with Chagas heart disease (n=22; 55% females; 65.5 years, SD 10.1) were included. Patients underwent high-resolution contrast-enhanced cardiac magnetic resonance using myocardial delayed enhancement with postprocessing analysis to identify the core scar area and border zone channels number, mass, and length. The association between border zone channel parameters and the combined end-point (cardiovascular mortality or internal cardiac defibrillator implantation) was tested by multivariable Cox proportional hazard regression analyses. The significance level was set at 0.05. Data are presented as the mean (standard deviation [SD]) or median (interquartile range).A total of 44 border zone channels (1[1-3] per patient) were identified. The border zone channel mass per patient was 1.25 (0.48-4.39) g, and the extension in layers of the border zone channels per patient was 2.4 (1.0-4.25). Most border zone channels were identified in the midwall location. Six patients presented the studied end-point during a mean follow-up of 4.9 years (SD 1.6). Border zone channel extension in layers was associated with the studied end-point independent from left ventricular ejection fraction or fibrosis mass (HR=2.03; 95% CI 1.15-3.60).High-resolution contrast-enhanced cardiac magnetic resonance can identify border zone channels in patients with Chagas heart disease. Moreover, border zone channel extension was independently associated with clinical events

Rats with high left ventricular end-diastolic pressure can be identified by Doppler echocardiography one week after myocardial infarction

The severity of left ventricular (LV) dysfunction in rats with myocardial infarction (MI) varies widely. Because homogeneity in baseline parameters is essential for experimental investigations, a study was conducted to establish whether Doppler echocardiography (DE) could accurately identify animals with high LV end-diastolic pressure as a marker of LV dysfunction soon after MI. Direct measurements of LV end-diastolic pressure were made and DE was performed simultaneously 1 week after surgically induced MI (N = 16) or sham-operation (N = 17) in female Wistar rats (200 to 250 g). The ratio of peak early (E) to late (A) diastolic LV filling velocities and the ratio of E velocity to peak early (Em) diastolic myocardial velocity were the best predictors of high LV end-diastolic pressure (>12 mmHg) soon after MI. Cut-off values of 1.77 for the E/A ratio (P = 0.001) identified rats with elevated LV end-diastolic pressure with 90% sensitivity and 80% specificity. Cut-off values of 20.4 for the E/Em ratio (P = 0.0001) identified rats with elevated LV end-diastolic pressure with 81.8% sensitivity and 80% specificity. Moreover, E/A and E/Em ratios were the only echocardiographic parameters independently associated with LV end-diastolic pressure in multiple linear regression analysis. Therefore, DE identifies rats with high LV end-diastolic pressure soon after MI. These findings have implications for using serial DE in animal selection and in the assessment of their response to experimental therapies.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de Fisiologia Cardiovascular e RespiratóriaUNIFESP, EPM, Depto. de MedicinaUNIFESP, EPM, Disciplina de Fisiologia Cardiovascular e RespiratóriaSciEL

Rats with high left ventricular end-diastolic pressure can be identified by Doppler echocardiography one week after myocardial infarction

The severity of left ventricular (LV) dysfunction in rats with myocardial infarction (MI) varies widely. Because homogeneity in baseline parameters is essential for experimental investigations, a study was conducted to establish whether Doppler echocardiography (DE) could accurately identify animals with high LV end-diastolic pressure as a marker of LV dysfunction soon after MI. Direct measurements of LV end-diastolic pressure were made and DE was performed simultaneously 1 week after surgically induced MI (N = 16) or sham-operation (N = 17) in female Wistar rats (200 to 250 g). The ratio of peak early (E) to late (A) diastolic LV filling velocities and the ratio of E velocity to peak early (Em) diastolic myocardial velocity were the best predictors of high LV end-diastolic pressure (>12 mmHg) soon after MI. Cut-off values of 1.77 for the E/A ratio (P = 0.001) identified rats with elevated LV end-diastolic pressure with 90% sensitivity and 80% specificity. Cut-off values of 20.4 for the E/Em ratio (P = 0.0001) identified rats with elevated LV end-diastolic pressure with 81.8% sensitivity and 80% specificity. Moreover, E/A and E/Em ratios were the only echocardiographic parameters independently associated with LV end-diastolic pressure in multiple linear regression analysis. Therefore, DE identifies rats with high LV end-diastolic pressure soon after MI. These findings have implications for using serial DE in animal selection and in the assessment of their response to experimental therapies.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de Fisiologia Cardiovascular e RespiratóriaUNIFESP, EPM, Depto. de MedicinaUNIFESP, EPM, Disciplina de Fisiologia Cardiovascular e RespiratóriaSciEL

LIMNOLOGIA DE TRÊS ECOSSISTEMAS AQUÁTICOS CARACTERÍSTICOS DA BAIXADA MARANHENSE

Durante dois anos (1997-99), foram estudadas as principais variáveis limnológicas dos três ecossistemas aquáticos mais representativos da Baixada Maranhense (1°59’ - 4°00’ S e 44°21’ - 45°33’ W). Tais sistemas, por serem inundáveis, apresentam extrema complexidade na estrutura e no funcionamento, sendo constituídos por: a) lagos rasos temporários que ocupam toda a área de campos abertos que se inundam no período das chuvas; b) lagos marginais; c) sistemas lacustres permanentes. A pesquisa abrangeu: os lagos de Viana/Cajari, os campos inundáveis da bacia do rio Perícumã e os lagos temporários da bacia do rio Turiaçu. O estudo pretendeu formar base cientificamente consistente de dados sobre limnologia dos ambientes com vistas a subsidiar um projeto de desenvolvimento sustentável da região, a qual vem sendo impactada por intervenções altamente perniciosas à sua ecologia, como a introdução de búfalos e de peixes exóticos, projetos de irrigação, barragens e comportas que alteram a hidrografia. As coletas foram feitas nos períodos: a) dos campos em inundação; b) inundação plena; c) inundação em declínio; d) estiagem plena. Em cada sistema, foram marcadas 5 estações onde foram estudados: transparência da água, perfil térmico e de radiação, pH, alcalinidade e C02 total, condutividade elétrica, oxigênio dissolvido, nutrientes, seston, clorofila, sedimentos e fauna ictiológica. As largas amplitudes do pH (5,13-9,60; 3,30-­6,30; 5,95-8,13), da condutividade (98-2800 mS.cm-1; 15-727 mS.cm-1; e 33-360 mS.cm-1) e da transparência da água (0,1-0,8 m; 0,3-4,0 m; 0,5-1,0 m) no lago de Viana, no rio Pericumã e no rio Turiaçu, respectivamente, refletem a elevada instabilidade desses ambientes, embora possuam muitas semelhanças físicas e biológicas, e estejam localizados na mesma região. Várias hipóteses estão sendo testadas para explicar essa instabilidade, especialmente os baixos níveis de pH. ABSTRACTLimnology of three aquatic ecosystems from Baixada Maranhense: preliminary dataDuring two years (1997-99), the main limnological parameters of the three more representative aquatic ecosystems from Baixada Maranhense were studied (1°59’ - 4°00’ S e 44°21’ - 45°33’ W). Such flooded systems present extreme complexity in structure and functioning, which are constituted by: a) temporary shallow lakes whose occupy all the floodplain area in the rainy period; b) marginal lakes; c) permanent lacustrine systems. This research extended over: Viana-Cajari lakes, Pericuma River floodplains and Turiaçu River temporary lakes. The study intended to form a scientifically consistent data base on the Limnology of the environments with the objective of serving to a project of regional sustainable development, which region has undergone interventions highly hazardous to its ecology, such as the introduction of indian buffalos and exotic fishes, irrigation projects, dams and floodgates that change local hydrography. Scientific excursions were done in the periods: a) beginning of flooding, b) maximum flooding; c) decline of flooding; d) maximum drought. The following parameters were studied in five sites of each system: Secchi dish measurements, thermal, and radiation profiles, pH, total alkalinity, electrical conductivity, dissolved oxygen, nutrients, particulate material, pigments and ichthyologic fauna. The great amplitudes of pH (5.13-9.60; 3.30-6.30; 5.95-8.13), electrical conductivity (98-2800 µS.cm-1; 15-727 µS.cm-1; 33-360 µS.cm-1) and water transparency (0.1-0.8 m; 0.3-4.0 m; 0.5-1.0 m) in Viana Lake, Pericumã River and Turiaçu River, respectively, reflect the high instability in these environments, although they are located in the same region. Some hypotheses are being tested to explain this instability, particularly in respect to the low levels of pH.Keywords: permanent and temporary lakes, ,floodplains, physico-chemical and biological parameters, Maranhão

Impact of COVID-19 In-hospital Mortality in Chagas Disease Patients

The COVID-19 virus infection caused by the new SARS-CoV-2 was first identified in Rio de Janeiro (RJ), Brazil, in March 2020. Until the end of 2021, 504,399 COVID-19 cases were confirmed in RJ, and the total death toll reached 68,347. The Evandro Chagas National Institute of Infectious Diseases from Oswaldo Cruz Foundation (INI-Fiocruz) is a referral center for treatment and research of several infectious diseases, including COVID-19 and Chagas disease (CD). The present study aimed to evaluate the impact of COVID-19 on in-hospital mortality of patients with CD during the COVID-19 pandemic period. This observational, retrospective, longitudinal study evaluated all patients with CD hospitalized at INI-Fiocruz from May 1, 2020, to November 30, 2021. One hundred ten hospitalizations from 81 patients with CD (58% women; 68 ± 11 years) were evaluated. Death was the study's main outcome, which occurred in 20 cases. The mixed-effects logistic regression was performed with the following variables to test whether patients admitted to the hospital with a COVID-19 diagnosis would be more likely to die than those admitted with other diagnoses: admission diagnosis, sex, age, COVID-19 vaccination status, CD clinical classification, and the number of comorbidities. Results from multiple logistic regression analysis showed a higher risk of in-hospital mortality in patients diagnosed with COVID-19 (OR 6.37; 95% CI 1.78–22.86) compared to other causes of admissions. In conclusion, COVID-19 infection had a significant impact on the mortality risk of INI-Fiocruz CD patients, accounting for one-third of deaths overall. COVID-19 presented the highest percentage of death significantly higher than those admitted due to other causes during the COVID-19 pandemic

The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance

Chagas disease (CD) affects at least 6 million people in 21 South American countries besides several thousand in other nations all over the world. It is estimated that at least 14,000 people die every year of CD. Since vaccines are not available, chemotherapy remains of pivotal relevance. About 30% of the treated patients cannot complete the therapy because of severe adverse reactions. Thus, the search for novel drugs is required. Here we tested the benznidazole (BZ) combination with the repositioned drug disulfiram (DSF) and its derivative diethyldithiocarbamate (DETC) upon Trypanosoma cruzi in vitro and in vivo. DETC-BZ combination was synergistic diminishing epimastigote proliferation and enhancing selective indexes up to over 10-fold. DETC was effective upon amastigotes of the BZ- partially resistant Y and the BZ-resistant Colombiana strains. The combination reduced proliferation even using low concentrations (e.g., 2.5 µM). Scanning electron microscopy revealed membrane discontinuities and cell body volume reduction. Transmission electron microscopy revealed remarkable enlargement of endoplasmic reticulum cisternae besides, dilated mitochondria with decreased electron density and disorganized kinetoplast DNA. At advanced stages, the cytoplasm vacuolation apparently impaired compartmentation. The fluorescent probe H2-DCFDA indicates the increased production of reactive oxygen species associated with enhanced lipid peroxidation in parasites incubated with DETC. The biochemical measurement indicates the downmodulation of thiol expression. DETC inhibited superoxide dismutase activity on parasites was more pronounced than in infected mice. In order to approach the DETC effects on intracellular infection, peritoneal macrophages were infected with Colombiana trypomastigotes. DETC addition diminished parasite numbers and the DETC-BZ combination was effective, despite the low concentrations used. In the murine infection, the combination significantly enhanced animal survival, decreasing parasitemia over BZ. Histopathology revealed that low doses of BZ-treated animals presented myocardial amastigote, not observed in combination-treated animals. The picrosirius collagen staining showed reduced myocardial fibrosis. Aminotransferase de aspartate, Aminotransferase de alanine, Creatine kinase, and urea plasma levels demonstrated that the combination was non-toxic. As DSF and DETC can reduce the toxicity of other drugs and resistance phenotypes, such a combination may be safe and effective