Blood Flows and Metabolic Components of the Cardiome

This is a plan for the first stage of The Cardiome Project. The cardiome is the representation, in quantitative, testable form, of the functioning of the normal heart and its responses to intervention. The goal is to integrate the efforts of many years into a comprehensive understandable scheme. Past efforts have spanned the fields of transport within blood vessels, the distributions of regional coronary blood flows, permeation processes through capillary and cell walls, mediated cell membrane transport, extra- and intracellular diffusion, cardiac electrophysiology, the uptake and metabolism of the prime substrates (fatty acid and glucose), the metabolism of the purine nucleosides and nucleotides (mainly adenosine and ATP), the regulation of the ionic currents and of excitation-contraction coupling and finally the regulation of contraction. The central theme is to define the coronary flows and metabolic components of a computer model that will become a part of a three-dimensional heart with appropriate fibre shortening and volume ejection. The components are: (a) coronary flow distributions with appropriate heterogeneity, (b) metabolism of the substrates for energy production, (c) ATP, PCr and energy metabolism and (d) calcium metabolism as it relates to excitation-contraction coupling. The modeling should provide: (1) appropriate responses to regional ischemia induced by constriction of a coronary artery, including tissue contractility loss and aneurysmal dilation of the ischemic region; (2) physiological responses to rate changes such as treppe and changes in metabolic demand and (3) changes in local metabolic needs secondary to changes in the site of pacing stimulation and shortening inactivation or stretch activation of contraction.