Sex-related differences in age-associated downregulation of human ventricular myocardial ß1-adrenergic receptors.

BACKGROUND: With increasing age, human ventricular myocardium exhibits selective downregulation of ß1-adrenergic receptors (ß1-ARs). We tested the hypothesis that sex differences exist in age-related changes in ß1-ARs. METHODS: Left (LV) and right (RV) ventricular tissue was obtained from 61 unplaceable potential organ donor hearts ages 1 to 71 years with no known cardiac history and from LVs removed from 56 transplant recipients with idiopathic dilated cardiomyopathy. ß1-AR and ß2-AR densities, the frequency of ß1-AR389 gene variants, and ß-AR function were determined. RESULTS: Sex had a marked effect on the age-related decrease in ß1-ARs. Female LVs had more pronounced downregulation (by 42% [p < 0.001] vs 22% [p = 0.21] in 31 male LVs) comparing the youngest (average age, 15.3 ± 5.5 years) to the oldest (average age, 50.8 ± 9.1 years) sub-groups. On regression analyses, female LVs exhibited a closer relationship between ß1-AR density and age (r = -0.78, p <0.001 vs r = -0.46, p = 0.009 in males), with a second-degree polynomial yielding the best fit. There was no statistically significant relationship of ß1-ARs to age in female or male idiopathic dilated cardiomyopathy LVs. CONCLUSIONS: Sex affects age-related ß-AR downregulation in normal human ventricles, with females exhibiting more profound decreases with increasing age. The curvilinear relationship between age and receptor density that plateaus around age 40 in women suggests an effect of sex hormones on ß1-AR expression in the human heart.

Intraoperative thrombosis of right coronary artery drug-eluting stent after 2 years of dual antiplatelet therapy.

This study presents the case of intraoperative thrombosis of a right coronary drug-eluting stent and subsequent right heart ischemia more than 2 years poststent placement and after recent withdrawal of clopidogrel therapy. Dual antiplatelet therapy had been continued uninterrupted since placement until 7 days prior to surgery when clopidogrel was stopped. This case highlights the emerging evidence that drug-eluting stents are susceptible to late occlusive thrombosis on acute withdrawal of antiplatelet therapy. Right heart ischemia resolved with rapid intraoperative management and emergent cardiac catheterization. This emphasizes the necessity of immediate availability to cardiac interventional facilities, which can influence outcomes.

Cystic appearance of low-grade endometrial stromal sarcoma in the right atrium: case report.

A 71-year-old woman presented with a right adnexal solid mass invading the right gonadal vein and inferior vena cava up to the hepatic veins revealed by CT and confirmed by MRI. A thin-walled cyst and a solid mass were unexpectedly found in the right atrium by transesophageal echocardiography (TEE) in the operating room. Using color Doppler and air bubbles as contrast material a circumscribed cyst was confirmed and localized close to the IVC. The cyst was connected to the mass in the inferior vena cava. The tumor, including the cyst, was removed without using cardiopulmonary bypass and described as a low-grade endometrial stromal sarcoma, a rare slowly growing tumor. This is the first TEE description of endometrial stromal sarcoma manifesting as a right atrial cyst.

Hypoplastic left heart syndrome myocytes are differentiated but possess a unique phenotype.

INTRODUCTION: Hypoplastic left heart syndrome (HLHS) is the term used to describe a group of congenital malformations characterized by marked underdevelopment of the left side of the heart. HLHS accounts for nearly 25% of cardiac deaths in the first year of life. Although much has been reported regarding diagnosis, gross morphology and surgical treatment, no information on gene expression in HLHS myocytes is available. METHODS: We examined heart tissue from patients with HLHS using routine histology, immunohistochemistry, quantitative polymerase chain reaction (PCR), two-dimensional (2-D) gel electrophoresis and protein identification by mass spectrometry. RESULTS: Histologic examination of right and left ventricles from HLHS patients revealed characteristic features of myocyte differentiation, including striations and intercalated disc formation. Immunohistochemical staining using antibody to N-cadherin demonstrated clear development of intercalated discs between myocytes. However, many of the myocytes contained scant cytoplasm and were grouped in small, disorganized bundles separated by abundant connective tissue and dilated, thin-walled vessels. Quantitative PCR analysis demonstrated that both left and right ventricular tissue from HLHS hearts expressed the fetal or "heart failure" gene expression pattern. Two-dimensional gel electrophoresis and protein identification by mass spectrometry also confirmed that myocytes from HLHS ventricles were differentiated but expressed the fetal isoform of some cardiac specific proteins. However, HLHS myocytes in all of the heart samples (n=21) were inappropriately expressing platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31), a member of the cell adhesion molecule (CAM) family that has a primary role in the regulation of tissue morphogenesis. These findings indicate that myocytes from HLHS syndrome patients, while differentiated, have a unique gene expression pattern.