Temporal Frame of Immune Cell Infiltration during Heart Failure Establishment: Lessons from Animal Models.

Heart failure (HF) is a cardiovascular syndrome characterized by maladaptive changes with an underlying inflammatory mediated pathogenesis. Nevertheless, current therapy is aimed at the heart workload and neurohormonal axis; thus, prognosis remains poor. To continue improving treatment, we rely on murine models for a better understanding of HF pathophysiology. Among them, pressure overload HF (PO-HF) animal models are a common strategy. Development of PO-HF is characterized by monocyte infiltration, which orchestrates a cascade of events leading to sustained inflammation and maladaptive changes. Here, we divide the PO-HF model progression into four phases and describe the inflammatory, structural, and gene expression profiles. This division is relevant due to its similarities with clinical hypertensive heart disease progression to HF. Evidence shows improvement in hemodynamic and other local parameters by altering the inflammatory response in a specific immune response at a specific point of time. Thus, it is relevant to focus on the time-dependent immune response interaction in order to provide more effective therapy. This review summarizes the pathogenesis of PO-HF murine models, highlighting the inflammatory events in a time frame view. By this approach, we expect to provide researchers with a better understanding of the intertwining time-dependent events that occur in PO-HF.

The Effects of Diabetes Induction on the Rat Heart: Differences in Oxidative Stress, Inflammatory Cells, and Fibrosis between Subendocardial and Interstitial Myocardial Areas.

Diabetic cardiomyopathy (DCM) is characterized by cardiac remodeling and impaired diastolic function that may lead to heart failure. The aim of this study was to evaluate oxidative stress, inflammatory cells, and fibrosis in both subendocardial (SEN) and interstitial (INT) areas of the myocardium. Male Wistar rats were allocated to 2 groups of 9 animals, a control (CT) group and streptozotocin-induced diabetes (DM). After 8 weeks, echocardiography morphometry, protein expression, and confocal microscopy in SEN and INT areas of the left ventricle (LV) were performed. The echocardiographic analysis showed that diabetes induction leads to cardiac dilation, hypertrophy, and LV diastolic dysfunction. As compared to CT, the induction of diabetes increased inflammatory cells and fibrosis in both SEN and INT areas of DM myocardium and increased ROS generation only in SEN. Comparing the SEN and INT areas in the DM group, inflammatory cells and fibrosis in SEN were greater than in INT. In conclusion, diabetic myocardium SEN area, wherein oxidative stress was more pronounced, is more susceptible to cardiac dysfunction than INT area. This finding can be important for the understanding of the heart remodeling process occurring in DCM and perhaps to engender targeted therapies to attenuate or revert DCM-related diastolic dysfunction.

Peripartum cardiomyopathy. Insights from Haiti regarding a disease of unknown etiology.

Peripartum cardiomyopathy (PPCM) is a disease of unknown etiology characterized by the onset of left ventricular failure during the period of 1 month antepartum to 5 months postpartum. The PPCM Project at Hospital Albert Schweitzer (HAS) in Haiti has identified 78 cases of PPCM since February 1, 2000, representing an incidence of 1 case per 350 to 400 live births, which is severalfold the estimated incidence in the United States. The reasons for this high incidence in Haiti are unknown. Ongoing investigations have identified the presence of several anticardiac antibodies in many women at HAS who have PPCM, suggesting that PPCM is a unique form of dilated cardiomyopathy and supporting the hypothesis that PPCM has an autoimmune basis. Identification of a high-incidence area for PPCM presents a unique opportunity to make progress in defining potential risk factors, identifying high-risk mothers, detecting underlying etiologies, and discovering more effective new treatments of this often-fatal disease.

[Humoral rejection in heart transplantation. Report of 2 cases]. / Rechazo humoral en trasplante cardíaco. Comunicación de dos casos.

Heart transplantation is a therapeutic alternative for selected patients with refractory heart failure. Acute allograft rejection is one of the main causes of early death after transplantation. The cellular rejection is characterized by cellular infiltrates with or without myocyte necrosis. However, some patients develop left ventricular dysfunction due to rejection without evidence of cellular infiltration. In these patients, the rejection is mediated by antibodies and complement. Humoral rejection is a relative rare but potentially fatal form of acute allograft rejection. We report two patients with left ventricular dysfunction secondary to humoral rejection, shortly after cardiac transplantation. Both patients were treated with methylprednisolone, and azathioprine was substituted by cyclophosphamide. One patient underwent plasmapheresis. The clinical outcome was satisfactory and the left ventricular function returned to normal in both cases. The diagnostic and therapeutic strategies for the management of humoral rejection are reviewed.

Doppler echocardiographic evaluation of HIV-positive patients in different stages of the disease.

OBJECTIVE: To evaluate by Doppler echocardiography (DE) early abnormalities of ventricular function in HIV-positive patients, as well as other cardiac abnormalities that can be detected by this method, with special emphasis on mitral valve flow. METHODS: 84 HIV-positive patients, 59 with CD4 cell count > 500/mm3 (Group A) and 25 with CD4 cell count < 500/mm3 (Group B), were analyzed. CD4 cells were counted and matched with structural data and systolic and diastolic function of the left ventricle (LV), as analyzed by DE. The results were compared with those obtained in 47 healthy individuals (Group C). RESULTS: 8% of patients in Group B had mild pericardial effusion; 31.5% showed decreased systolic function of the LV, and 12% had moderate mitral regurgitation. A wave velocity from the mitral inflow was different among the 3 groups, being higher in Group B, where the deceleration time of the E wave of the mitral inflow and the E/A ratio were significantly lower with a normal value of the isovolumic relaxation time (IVRT). CONCLUSION: HIV-positive patients with a CD4 cell count > 500/mm3 had no abnormalities by DE. Patients with a more advanced infection (those with a CD4 cell count < 500/mm3), had a significantly abnormal LV systolic function and a higher incidence of pericardial effusion and mitral regurgitation. Mitral valve inflow by Doppler did not indicate diastolic dysfunction.

Reposta proliferativa das células T contra a cruzipaina na cardiopatia chagásica crônica / T cells proliferative responses to cruzipaina in chronic chagasic cardiopathy

In this paper, we sought to determine if chronic chagasic patients with cardiopathy could be distinguished from those displaying non-chagasic cardiopathy on the basis of T cell proliferative responses to cruzipain (GP57/51), a major antigen of T. cruzi. Assays were performed with peripheral blood mononuclear cells from 24 individuals classified as follows: normal donors (n = 8), patients with non-chagasic cardiopathy (n = 8), patients with chronic chagasic cardiopathy without morbid associations (n = 8). The analysis of variance indicated that the proliferative responses stimulated by cruzipain were significantly higher in the group of chagasic patients (p = 0.0001). Turkey's multiple comparison test showed that the proliferative index medium from normal and non-chagasic cardiopathy was not significantly different from each other. We conclude that the T cell responses against T. cruzipain, as measured by proliferative indices of cells found in peripheral blood, are exclusively associated with Chagas, disease. In view of the abundance of cruzipain antigen in amastigotes it is possible that these T cell specificities contribute to the heart tissue damage observed in chronic Chagas, disease patients.

[The proliferative response of T cells against cruzipain in chronic chagasic cardiopathy]. / Reposta proliferativa das células T contra a cruzipaina na cardiopatia chagásica crônica.

In this paper, we sought to determine if chronic chagasic patients with cardiopathy could be distinguished from those displaying non-chagasic cardiopathy on the basis of T cell proliferative responses to cruzipain (GP57/51), a major antigen of T. cruzi. Assays were performed with peripheral blood mononuclear cells from 24 individuals classified as follows: normal donors (n = 8), patients with non-chagasic cardiopathy (n = 8), patients with chronic chagasic cardiopathy without morbid associations (n = 8). The analysis of variance indicated that the proliferative responses stimulated by cruzipain were significantly higher in the group of chagasic patients (p = 0.0001). Turkey's multiple comparison test showed that the proliferative index medium from normal and non-chagasic cardiopathy was not significantly different from each other. We conclude that the T cell responses against T. cruzipain, as measured by proliferative indices of cells found in peripheral blood, are exclusively associated with Chagas, disease. In view of the abundance of cruzipain antigen in amastigotes it is possible that these T cell specificities contribute to the heart tissue damage observed in chronic Chagas, disease patients.

[Left ventricular thrombosis complicating systemic lupus erythematosus]. / Thrombus intraventriculaire gauche compliquant une maladie lupique.

The authors report an isolated pediculated thrombus in the left ventricle of a young 14 year old girl with systemic lupus erythematosus with antiphospholipid antibodies without any other cardiovascular abnormality, especially ventricular wall motion abnormalities. After surgical ablation of the thrombus, the patient was followed up to avoid recurrence. This type of cardiac lesion (ventricular thrombosis without underlying myocardial disease) is exceptionally rare. Echocardiographic follow-up after surgical ablation showed no recurrence of thrombosis after four years.