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Heart & Vascular Institute

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Weiss Lab Projects

Coronary Endothelial Function

Coronary vascular function plays a critical role in the development, progression, and clinical manifestations of coronary artery disease. One defining characteristic of non-diseased vascular tissue is endothelial release of nitric oxide which inhibits platelet aggregation, attenuates inflammation, decreases cellular proliferation, and induces local vascular smooth muscle vasodilation.  The latter effect has been used to assess vascular function for over two decades, by describing the direction and magnitude of changes in arterial diameter and flow velocity in response to endothelial-dependent vasomotor interventions.   We are developing ways to non-invasively measure coronary endothelial function for the first time in people in order to characterize the extent of endothelial dysfunction in patients with coronary  disease as well as those at risk for its development. 

Human Heart Failure:  Is the Failing Heart Energy Starved?

Chemical energy in the form of ATP fuels the heart’s continuously beating engine that pumps blood to the body.  As a result the chemical energy demands of the heart are the highest of any organ in the body.  Our laboratory is interested in the chemical reactions or metabolic pathways in the heart that generate ATP and the ways those reactions are altered by common diseases as well as ways abnormalities in energy-generating metabolic pathways adversely affect heart function.  The creatine kinase reaction is the prime energy reserve of the heart and abnormalities in creatine kinase are observed in experimental and human heart failure.   We are investigating whether a decrease in ATP production through the creatine kinase reaction is an important factor causing poor pump function in heart failure.

Specifically we are studying ATP and the creatine kinase reaction in mice and people with heart failure.  In people we measure cardiac ATP and ATP flux through the creatine kinase reaction with magnetic resonance (MR) techniques.   From the first measures of the rate of ATP turnover through creatine kinase in the human heart, we have shown that ATP flux through the creatine kinase reaction is reduced in the most common forms of human heart failure, is deceased in both systolic and in diastolic dysfunction, and is one of the most severe energetic abnormalities.  To determine whether an abnormality in energy production or transfer causes pump dysfunction in heart failure we are using genetic manipulation techniques in animals and MR methods to determine the functional consequences of improving metabolism.  Thus studies from literally mice to humans probing cardiac metabolism in heart failure are occurring in our laboratory.  

Echocardiogram from a patient with hypertrophy and corresponding spectra Figure: Axial spin-echo MR image (A)of a patient with hypertrophy and heart failure lying prone over a 31P surface coil (white box) and the corresponding localized 31P MR spectra from the chest (lower 2 spectra) and left ventricle (upper 2 spectra).  The spectra were acquired with a 60° flip angle in the presence of chemically selective saturating irradiation (arrows) either in the control (B) or ?-ATP position (C). The decrease in the height of the PCr peak between control and ?-ATP saturation (dotted lines) is directly related to the rate of ATP synthesis through the CK reaction.  (from Smith et al Circulation 2006)