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Background With increasing age, human ventricular myocardium exhibits selective downregulation of β 1 -adrenergic receptors (β 1 -ARs). We tested the hypothesis that sex differences exist in age-related changes in β 1 -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. β 1 -AR and β 2 -AR densities, the frequency of β 1 - AR389 gene variants, and β-AR function were determined. Results Sex had a marked effect on the age-related decrease in β 1 -ARs. Female LVs had more pronounced downregulation (by 42% [ p 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 β 1 -AR density and age ( r = –0.78, p r = –0.46, p = 0.009 in males), with a second-degree polynomial yielding the best fit. There was no statistically significant relationship of β 1 -ARs to age in female or male idiopathic dilated cardiomyopathy LVs. Conclusions Sex affects age-related β-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 β 1 -AR expression in the human heart.

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.

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.