Diastolic Heart Failure

Diastolic heart failure afflicts about 2.5 million Americans and describes a situation in which the heart has a normal ejection fraction (>0.50) but is unable to pump blood at a sufficient rate to meet the body's basal metabolic demands. This often reflects a situation in which the ventricles are too stiff to distend fully at normal filling pressures.

Our lab is interested in trying to understand which molecular components are responsible for the excessive stiffness in different forms of diastolic heart failure.

The experimental techniques we use include:

Animated sequence showing cell stretching

Mechanical measurements with single cardiac cells

We measure the mechanical properties of single cardiac cells by gluing them between a force transducer and a motor and measuring the force produced as the cells are stretched. Sarcomere length is calculated automatically by fitting damped sine-wave functions to the autocorrelation of the striation pattern.

Force records from a rat multicellular preparation

Mechanical measurements with multicellular preparations

We can also measure the mechanical properties of chemically permeabilized multicellular preparations when they are activated in solutions with different free Ca²⁺ concentrations. Custom-written software is used to analyze the records and deduce parameters such as short-range stiffness, rate of tension recovery etc.

Schematic of whole heart apparatus

Mechanical measurements with Langendorff-perfused hearts

Eric Reid, an ex-Campbell Lab undergraduate student, developed a technique to measure ventricular stiffness in an isolated perfused rat heart. This project was further developed by Jenn Peterson, a subsequent undergraduate student, and is now being run by Premi Shekar.

GelBandFitter

Biochemistry

We are also interested in using techniques such as electrophoresis to analyze the protein content of the myocardium tissue in different forms of cardiovascular disease. GelBandFitter is a computer program that we developed to get better estimates of the relative content of two proteins when they run as overlapping bands on a conventional gel.