Publications

Depression is associated with increased morbidity and mortality in patients with coronary heart disease (CHD). Increased platelet activation has been proposed as a potential mechanism by which depression may lead to adverse cardiovascular outcomes. In this cross-sectional study, we measured platelet activation in 104 patients with stable CHD, including 58 with a current episode of major depression and 46 without past or current major depression. Participants were instructed not to take aspirin for 7 days prior to the study appointment. Platelet activation was measured by plasma concentrations of platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG), and by 24-h urinary concentrations of 11-dehydro-thromboxane B(2) (TBXB2). We observed no differences in the mean levels of PF4, B-TG or TBXB2 in patients with and without major depression. Results were unchanged after adjustment for age, smoking, use of aspirin, and use of any psychotropic medication. We found no evidence of an association between major depression and platelet activation as measured by plasma concentrations of PF4 and beta-TG, or urinary TBXB2 in 104 outpatients with stable CHD. These findings do not support a role for platelet activation in the association between depression and cardiovascular disease among patients with stable CHD.

BACKGROUND

Microcomputed tomography (micro-CT) has been used extensively in research to generate high-resolution 3D images of calcified tissues in small animals nondestructively. It has been especially useful for the characterization of skeletal mutations but limited in its utility for the analysis of soft tissue such as the cardiovascular system. Visualization of the cardiovascular system has been largely restricted to structures that can be filled with radiopaque intravascular contrast agents in adult animals. Recent ex vivo studies using osmium tetroxide, iodinated contrast agents, inorganic iodine, and phosphotungstic acid have demonstrated the ability to stain soft tissues differentially, allowing for high intertissue contrast in micro-CT images. In the present study, we demonstrate the application of this technology for visualization of cardiovascular structures in developing mouse embryos using Lugol solution (aqueous potassium iodide plus iodine).

METHODS AND RESULTS

We show the optimization of this method to obtain ex vivo micro-CT images of embryonic and neonatal mice with excellent soft-tissue contrast. We demonstrate the utility of this method to visualize key structures during cardiovascular development at various stages of embryogenesis. Our method benefits from the ease of sample preparation, low toxicity, and low cost. Furthermore, we show how multiple cardiac defects can be demonstrated by micro-CT in a single specimen with a known genetic lesion. Indeed, a previously undescribed cardiac venous abnormality is revealed in a PlexinD1 mutant mouse.

CONCLUSIONS

Micro-CT of iodine-stained tissue is a valuable technique for the characterization of cardiovascular development and defects in mouse models of congenital heart disease.