The Cardiome Project. An integrated view of cardiac metabolism and regional mechanical function

Abstract

The goal, to develop a functioning three-dimensional computational model of the excitation, metabolism and contraction of the heart within three years, is one of the beginnings for the Cardiome Project. Our first stage will not be likely to provide highly accurate prediction of physiological behavior in general, but will be focussed so that it is adequate for at least three specific purposes: response to regional flow reduction, response to heart rate changes, and response to increased metabolic drive. We would like to make the model visualizable by three-dimensional viewing, with cross-sectional and transparency viewing approaches, illustrate the fiber directions, the arteries, the deformation with contraction and images of regional functions such as oxygen consumption, preejection strain, or lactate concentration. The display techniques developed by Hunter et al. and by McCulloch et al. would be excellent for such demonstration and teaching purposes, and should be attractive enough for public display. The Physiome Project is underway now, with growing government and private support. Now we are going from the era of molecular biology, led by the Genome Project, into a new era of integrative biology. The goal is to understand biology so deeply and so broadly that predictions about interventions can be made. Methods of experimentation and of diagnosis are critical to acquiring the data, and therefore in making the prediction, and so all aspects of our Society's efforts and interests are relevant to undertaking this grand challenge.

Figure 1

Overall diagram of the Cardiome Model components.

Figure 2

Dual capillary-tissue model for ¹⁵O-oxygen transport and metabolism into ¹⁵O-water. The four concentric regions are red blood cells (rbc), plasma (p), interstitial fluid (isf) and parenchymal cells (pc). The symbols used are F for flow, ml min⁻¹g⁻¹; V for anatomical volumes and V’ for volumes of distribution, ml g⁻¹; PS for permeability-surface area product, ml min⁻¹g⁻¹; G for the first-order consumption rate, ml min⁻¹g⁻¹; and D for the axial dispersion coefficient, cm² s⁻¹. The superscripted “o” and “w” denote oxygen and water, respectively.

Figure 3

Correlation between blood flow (rMBF) and oxygen consumption (rMRO₂) in regions of interest (0.9 ± 0.3 g) of the LV myocardium of a closed-chest dog.