Pathogenesis Of Cardiac Involvement Research Articles

Cardiac Manifestations in Systemic Lupus Erythematosus: A Case Report and Review of the Literature.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical features and variable clinical course. SLE tends to affect women during childbearing years and is characterized by multi-organ involvement. Cardiac complications in SLE, which have been described to occur in about 50% of the cases, contributes to significant morbidity and mortality in this population. We describe a patient with SLE and established lupus nephritis who subsequently developed cardiac manifestations including valvular abnormalities, arrythmia and end stage heart failure. The clinical features, work up and management will be discussed. A 35 year-old African American woman diagnosed with SLE in her twenties presented to our hospital for evaluation of shortness of breath. After SLE diagnosis, the patient had been prescribed hydrochloroquine and low dose steroids for joint and skin manifestations. Four years after initial presentation, she developed biopsy proven lupus nephritis for which standard induction therapy was administered. She was placed on maintenance immunosuppression with stable renal function. On admission, the patient's symptoms included dyspnea on exertion, chest pain, palpitations, and a non-productive cough. Initial evaluation identified atrial fibrillation and new onset of heart failure given elevated brain natriuretic peptide (BNP) levels and left ventricular ejection fraction (EF) of 15% by echocardiogram. Cardiac catheterization revealed global hypokinesis and non-obstructive coronary artery disease (CAD). The patient was deemed not a suitable candidate for cardiac transplant and was offered a life vest as bridging to an implantable cardioverter (ICD). Twenty-four months after discharge, the patient continued to be managed medically and has not had any subsequent hospitalizations. Cardiac complications, reported in about 50% of SLE patients, are associated with high morbidity and mortality. Pericarditis is the most common, however conduction defects, valvular damage and heart failure are also observed among SLE patients. The pathogenesis of cardiac involvement seems to be multifactorial. The management of heart failure in SLE entails medical therapy and implantable device use. Further research is needed to explore new options to arrest the development and progression of cardiac disease among lupus patients.

Heart‐ and skeletal muscle‐specific antigens recognized by trichinellosis patient sera

The heart can be seriously affected in human trichinellosis, and cardiac involvement can cause death. Experimental infections in rats have suggested the possible participation of immunopathological processes. The aim of the present paper was to investigate the possible presence in trichinellosis patient sera of antibodies recognizing host tissues and particularly the myocardium. Nineteen sera from late period trichinellosis patients, who acquired infection in the Poznan region (Poland), were tested by immunoblot on extracts from normal rat or human heart ventricle wall, spleen, placenta, kidney and skeletal muscle. Patients' sera recognized several antigens that were not recognized by normal sera. On rat and human heart ventricle wall, a high proportion of sera (42%) reacted with a protein of 68 kDa (P < 0.05 compared to normal sera). The reactivity with this antigen, however, was not significantly different in patients with or without cardiac involvement. When sera were tested on skeletal muscle we found that 47% reacted with a protein of 27 kDa and 53% reacted with a protein of 41 kDa (P < 0.05 for both proteins, compared with normal sera). The reactivity against the 68 kDa antigen and against the 27 and 41 kDa skeletal muscle antigens was not observed on kidney, placenta and spleen extracts. Moreover, very few bands were observed on these tissues as compared to heart and skeletal muscle tissues, thus suggesting a high tissue specificity of the reactivity of trichinellosis sera. In conclusion, this study identifies organ-specific autoantibodies in trichinellosis patient sera, their role in the pathogenesis of cardiac involvement being still unclear.

Diabetes-induced Myocardial Structural Changes: Role of Endothelin-1 and its Receptors

S. Chen, T. Evans, K. Mukherjee, M. Karmazyn and S. Chakrabarti. Diabetes-induced Myocardial Structural Changes: Role of Endothelin-1 and its Receptors. Journal of Molecular and Cellular Cardiology (2000) 32, 1621–1629. Several metabolic abnormalities may be triggered secondary to hyperglycemia in diabetes. Some of these abnormalities may alter expression of vasoactive factors in the target organs of diabetic complications. We investigated alterations of endothelin-1 (ET-1) and its receptors, ETAand ETB, and associated structural changes in the myocardium of streptozotocin-induced diabetic rats after 6 months of hyperglycemia. We further assessed the preventive effects of an ET-receptor antagonist bosentanTMon these changes. Compared to the non-diabetic, age- and sex-matched control animals, diabetic rats showed hyperglycemia, glucosuria, reduced body weight gain and elevated glycated Hb levels. Measurement of ET-1, ETAand ETBmRNAs by semiquantitative RT-PCR showed significantly increased mRNA levels in the hearts of diabetic rats. Treatment with bosentanTMfailed to reduce ET-1 or ETBmRNA expression in diabetes, however ETAmRNA expression was reduced. Immunocytochemically, ET-1 was detected in the cardiomyocytes, endothelium and smooth muscle cells of the larger blood vessels and was increased in diabetes. Autoradiographic localization of ET-1 receptors, using125I-ET-1, showed increased binding in the endothelium and myocardium of diabetic animals. Histologically, focal fibrous scarring with apoptotic cardiomyocytes, consistent with changes secondary to microvascular occlusion, was only present in the diabetic rats. In keeping with focal fibrosis, myocardium from diabetic rats further showed significantly increased mRNA expression of two extracellular matrix protein transcripts, fibronectin and collagen α 1(IV) which were completely prevented by treatment with bosentanTM. These data suggest that hyperglycemia-induced upregulation of the ET-system in the heart may be important in the pathogenesis of cardiac involvement in diabetes.