Biomarkers of cardio-renal syndrome in uremic myocardiopathy animal model / Biomarcadores de síndrome cardiorrenal em modelo animal de miocardiopatia urêmica

ABSTRACT Introduction: Cardio-renal syndrome subtype 4 (CRS4) is a condition of primary chronic kidney disease that leads to reduction of cardiac function, ventricular hypertrophy, and risk of cardiovascular events. Objective: Our aim was to understand the mechanisms involved on the onset of CRS4. Methods: We used the nephrectomy 5/6 (CKD) animal model and compared to control (SHAM). Serum biomarkers were analyzed at baseline, 4, and 8 weeks. After euthanasia, histology and immunohistochemistry were performed in the myocardium. Results: Troponin I (TnI) was increased at 4 weeks (W) and 8W, but nt-proBNP showed no difference. The greater diameter of cardiomyocytes indicated left ventricular hypertrophy and the highest levels of TNF-α were found at 4W declining in 8W while fibrosis was more intense in 8W. Angiotensin expression showed an increase at 8W. Conclusions: TnI seems to reflect cardiac injury as a consequence of the CKD however nt-proBNP did not change because it reflects stretching. TNF-α characterized an inflammatory peak and fibrosis increased over time in a process connecting heart and kidneys. The angiotensin showed increased activity of the renin-angiotensin axis and corroborates the hypothesis that the inflammatory process and its involvement with CRS4. Therefore, this animal study reinforces the need for renin-angiotensin blockade strategies and the control of CKD to avoid the development of CRS4.

RESUMO Introdução: A síndrome cardiorrenal (SCR) tipo 4 é uma afecção da doença renal crônica primária que leva a redução da função cardíaca, hipertrofia ventricular e risco de eventos cardiovasculares. Objetivo: O objetivo do presente estudo foi compreender os mecanismos envolvidos no surgimento da SCR tipo 4. Métodos: Um modelo animal de nefrectomia 5/6 (DRC) foi comparado a animais de controle (Placebo). Biomarcadores séricos foram analisados no início do estudo e com quatro e oito semanas de estudo. Após eutanásia, foram realizados exames histológicos e de imunoistoquímica no tecido miocárdico. Resultados: Troponina I (TnI) estava aumentada nas semanas quatro (S4) e oito (S8), mas o NT-proBNP não apresentou diferenças. O diâmetro maior dos cardiomiócitos indicava hipertrofia ventricular esquerda. Os níveis mais elevados de TNF-α foram identificados na S4 com redução na S8, enquanto fibrose foi mais intensa na S8. A expressão de angiotensina mostrou elevação na S8. Conclusões: TnI parece sugerir lesões cardíacas em consequência da DRC, porém o NT-proBNP não sofreu alterações por refletir alongamento. O TNF-α evidenciou um pico inflamatório e a fibrose aumentou ao longo do tempo devido ao processo de conexão entre rins e coração. A angiotensina mostrou aumento da atividade do eixo renina-angiotensina, corroborando a hipótese do processo inflamatório e seu envolvimento com SCR tipo 4. Portanto, o presente estudo em modelo animal reforça a necessidade de em adotar estratégias com bloqueadores de renina-angiotensina e controle da DRC para evitar o desenvolvimento de SCR tipo 4.

Ecocardiografia nas doenças não-coronárias / Role of echocardiography in noncoronary diseases

A ecocardiografia representa hoje técnica não-invasiva de investigação diagnóstica amplamente empregada na avaliação de pacientes portadores de valvopatias, de cardiomiopatias não relacionadas a doença arterial coronária, assim como de indivíduos apresentando doenças do pericárdio. A ecocardiografia caracteriza-se por ser método de investigação cardíaca anatômica não-invasiva, não-radioativa, apresentando alta reprodutibilidade, fácil acesso, baixo custo e grande correlação com métodos invasivos hemodinâmicos de aferição de pressões cardíacas...

Chronic eosinophilic leukemia with a unique translocation.

We report a case of chronic eosinophilic leukemia in a 9 year old girl who presented with anemia, thrombocytopenia, leucocytosis (mostly dysplastic eosinophils), lymphadenopathy and hepatosplenomegaly. There was no increase in blasts but myelofibrosis was seen in the bone marrow. A previously unreported translocation 46,XX,t(1;4)(q24;q35), was found on cytogenetic analysis and involvement of the myocardium was also present. Shortly after commencing steroids, the family abandoned therapy.

Electrocardiographic and echocardiographic changes in perinatal asphyxia.

OBJECTIVE: To study the usefulness of cardiac enzymes in evaluating myocardial damage in perinatal asphyxia. METHODS: Thirty term babies with perinatal asphyxia and without any congenital malformations were selected as cases. They were compared with thirty healthy term babies without asphyxia. Myocardial dysfunction was evaluated using clinical, electrocardiography, echocardiography and cardiac enzymes i.e, troponin-T and CK-MB levels. RESULTS: Among the 30 cases 23 had evidence of myocardial involvement while one baby in the control group had ECG evidence compatible with cardiac involvement. Cardiac enzymes were significantly increased in babies with perinatal asphyxia. The mean level of C-troponin-T among cases and controls were 0.22+/-0.28 and 0.003+/-0.018 while CK-MB levels were 121+/-77.4 IU/L and 28.8 +/- 20.2 IU/L respectively. C-troponin-T had higher sensitivity and specificity compared to CK-MB levels. Moreover, C troponin-T levels correlated well with severity and outcome in babies with perinatal asphyxia. CONCLUSION: C-Tropopnin assay is useful in evaluating the severity of myocardial damage and outcome in perinatal asphyxia.

Circulating adhesion molecules in patients with Keshan disease and their relationship with Coxsackie B virus infection / 华中科技大学学报（医学）（英德文版）

This study determined the levels of serum soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecular-1 (sVCAM-1) in patients with different types of Keshan disease (KD), examined the relationship between Coxsackie B virus-specific IgM antibody (CBV-IgM) and sICAM-1 or sVCAM-1 in KD patients, and investigated the role of these adhesion molecules in the pathogenesis of KD and their clinical implications. The levels of serum sICAM-1, sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in 22 patients with chronic Keshan disease (CKD), 27 with latent Keshan disease (LKD) and 28 healthy controls. The subjects in different groups were adjusted for sex and age. Echocardiography was adopted to determine left ventricular ejection fraction (LVEF) in 22 patients with CKD. The results showed that CKD patients had significantly higher levels of sICAM-1 and sVCAM-1 than LKD patients and healthy controls (P<0.01 for all). And there was significant difference in the levels of the 2 adhesion molecules between LKD patients and healthy controls (P<0.05). A negative correlation was found between LVEF and sICAM-1 or sVCAM-1 in CKD patients. The percentage of CBV-specific IgM positive individuals in KD patients was significantly higher than that of healthy controls. In CVB-specific IgM positive patients, the levels of serum sICAM-1 and sVCAM-1 were significantly greater than those in CBV-specific IgM negative counterpart. It was concluded that the increase in the levels of sICAM-1 and sVCAM-1 suggests the progression of inflammation in KD. sICAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function. The increased serum sICAM-1 and sVCAM-1 in KD patients may be related to CBV infection.

Níveis séricos de NT pro-BNP: relação com função sistólica e diastólica nas miocardiopatias e pericardiopatias / Serum NT pro-BNP: relation to systolic and diastolic function in cardiomyopathies and pericardiopathies

FUNDAMENTO: O NT pro-BNP é marcador de disfunção sistólica e diastólica. OBJETIVO: Determinar os níveis de NT pro-BNP em pacientes com cardiopatia chagásica, hipertrófica, restritiva e afecções pericárdicas, e sua relação com medidas ecocardiográficas de disfunção sistólica e diastólica. MÉTODOS: Cento e quarenta e cinco pacientes foram divididos nos respectivos grupos: 1) cardiopatia chagásica (CCh) - 14 pacientes; 2) miocardiopatia hipertrófica (CMH) - 71 pacientes; 3) endomiocardiofibrose (EMF) - 26 pacientes; 4) derrame pericárdico (DP) - 18 pacientes; 5) e pericardite constritiva (PC) - 16 pacientes. Foi constituído um grupo-controle de 40 indivíduos sem doença cardíaca. O grau de acometimento miocárdico e o derrame pericárdico foram avaliados pelo ecocardiograma bidimensional e a restrição pelo Doppler pulsátil do fluxo mitral. O diagnóstico de PC foi confirmado por meio da ressonância magnética. Os níveis de NT pro-BNP foram medidos por imunoensaio com detecção por eletroquimioluminescência. RESULTADOS: O NT pro-BNP esteve aumentado (p < 0,001) na CCh (mediana 513,8 pg/ml), CMH (mediana 848 pg/ml), EMF (mediana 633 pg/ml), PC (mediana 568 pg/ml), DP (mediana 124 pg/ml), quando comparados ao grupo-controle (mediana 28 pg/ml). Não foram observadas diferenças estatisticamente significativas entre PC e EMF (p = 0,14). No grupo hipertrófico, o NT pro-BNP correlacionou-se com tamanho de átrio esquerdo (r = 0,40; p < 0,001) e relação E/Ea (p < 0,01). No grupo restritivo, houve uma tendência de correlação com pico de velocidade de onda E (r = 0,439; p = 0,06). CONCLUSÃO: O NT pro-BNP encontra-se aumentado nas diversas miocardiopatias e afecções pericárdicas, e apresenta relação com o grau de disfunção sistólica e diastólica.

BACKGROUND: NT pro-BNP is a marker of systolic and diastolic dysfunction. OBJECTIVE: To determine NT pro-BNP levels in patients with chagasic, hypertrophic, and restrictive heart diseases, as well as with pericardial diseases, and their relation to echocardiographic measurements of systolic and diastolic dysfunction. METHODS: A total of 145 patients were divided into the following groups: 1) Chagas' heart disease (CHD) - 14 patients; 2) hypertrophic cardiomyopathy (HCM) - 71 patients; 3) endomyocardial fibrosis (EMF) - 26 patients; 4) pericardial effusion (PE) - 18 patients; and 5) constrictive pericarditis (CP) - 16 patients. The control group was comprised of 40 individuals with no heart disease. The degree of myocardial impairment and pericardial effusion were assessed by two-dimensional echocardiography and the degree of restriction by pulsed Doppler transmitral flow. The diagnosis of CP was confirmed through magnetic resonance imaging. NT pro-BNP levels were determined through electrochemiluminescence immunoassay. RESULTS: NT pro-BNP was increased (p < 0.001) in CHD (median = 513.8 pg/ml), HCM (median = 848 pg/ml), EMF (median = 633 pg/ml), CP (median = 568 pg/ml), and PE (median = 124 pg/ml), when compared with the control group (median = 28 pg/ml). No statistically significant differences were found between CP and EMF (p = 0.14). In the hypertrophic group, NT pro-BNP was correlated with left atrial size (r = 0.40; p < 0.001) and with E/Ea ratio (p < 0.01). In the restrictive group, there was a trend of correlation with E-wave peak velocity (r = 0.439; p = 0.06). CONCLUSION: NT pro-BNP is increased in the different cardiomyopathies and pericardial diseases and is correlated with the degree of systolic and diastolic dysfunction.

Serum zinc level in dilated and ischemic cardiomyopathy

Serum trace element alteration has been reported in dilated and ischemic cardiomyopathy. The reports were controversial. We have studied serum Zinc level in cardiomyopathy patients in northern province of Mazandaran and compared them with healthy volunteers. Serum Zinc level was measured in 30 ischemic and 18 dilated cardiomyopathy patients against 27 healthy volunteers. It was measured using atomic absorption spectrophotometry. Statistical analysis was performed using SPSS for Windows version 14 and independent t-test was used for comparing serum Zinc level in ischemic and dilated cardiomyopathy. Pearson correlation and ANOVA tests were used for numeric variables in three different groups. P<0.05was considered as statistically significant. The mean serum Zinc level was 0.97 +/- 0.25, 1.05 +/- 0.27, 1.21 +/- 0.42 mg/L for idiopathic dilated cardiomyopathy, ischemic cardiomyopathy and healthy volunteers respectively. There was no significant difference between three groups. There was also no correlation between echocardiography data and serum Zinc level. This study showed serum Zinc level might not have a role in pathogenesis of ischemic and dilated cardiomyopathy. As intracellular Zinc level play a role in heart subjected to ischemia- reperfusion, measuring intracellular Zinc may give us a better clue about role of Zinc or other trace elements in pathogenesis of cardiomyopathy

Leukotrienes excretion in acute myocardial ischemia

The role of leukotrienes, released at the site of myocardial ischemia, in attraction of neutrophils and contribution in cardiac dysfunction were suggested. Leukotrienes, having rapid metabolism and excretion, are difficultly measured in blood, their major metabolite leukotriene E4 [LTE4] detected in urine is a sensitive index for their production. In this study, the evaluation of the role of LTE4 measured in urine as an index for acute myocardial ischemia. Patients admitted to ICU complaining of acute myocardial ischemia were subdivided into group 1 [15 patients with acute myocardial infraction], group 2 [10 patients with unstable angina], control group [4 patients with chronic stable myocardial ischemia and 5 normal controls]. All patients and controls were subjected to clinical, ECG and echocardiographic examination, together with laboratory measurement of serum cardiac enzymes and urinary ITE4 by ELISA technique. The results demonstrated higher concentration of LTE4 in urine samples from AMI subjects 8 +/- 2 hours after infarction compared with samples collected two days later. A similar significant increase in LTE4 was observed in acute angina group. Two patients were given omega 3 fatty acids [EPA] for one month in a trial to lower urinary LTE4. The results were equivocal