Partial list of projects:

1. The timing of surgery in patients with chronic mitral regurgitation is problematic. Although the ventricle seems to contract extremely well as tested by echocardiograms, an examination of single cells from these ventricles (by force-frequency relationships) show that the cells are phenotypically failing. We will study the events taking place over time, and try to find a non-invasive marker of impending failure for affected patients by analyzing changes in:

a. Function (whole ventricle by end-systolic pressure-volume relationship, echocardiography),
b. Tissue composition (apoptosis, intracellular signaling mechanisms, extra cellular matrix and MMPs), and
c. The general "milieu," involving the activation of "inflammatory" factors (TNF, IL-6) and neuro-humoral factors (BNP, Angiotensin, ET-1, etc.).

2. A study of the interaction between endothelin, a very potent vasoconstrictor, and C-type natriuretic peptide (CNP), both paracrine factors secreted by endothelial cells and cardiac myocytes, acting on neighboring cells should lead to insights into cardiac dysfunction such as congestive heart failure, ventricular overload and hypertrophy, diastolic dysfunction and cardiomyopathy.

While CNP reduces myocyte contraction amplitude, endothelin abolishes this effect. We intend to investigate the modulating effect of endothelin on the inotropic effect of CNP and gain insights into the mechanisms involved.