BLOOD FLOWS AND METABOLIC COMPONENTS OF THE CARDIOME

This is a plan for the first stage of The Cardiome Project. The cardio me is the representation, in quantitative, testable form, of the funct ioning of the normal heart and its responses to intervention. The goal is to integrate the efforts of many years into a comprehensive unders tandable scheme. Past efforts have spanned the fields of transport wit hin 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 electr ophysiology, the uptake and metabolism of the prime substrates (fatty acid and glucose), the metabolism of the purine nucleosides and nucleo tides (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 met abolic components of a computer model that will become a part of a thr ee-dimensional heart with appropriate fibre shortening and volume ejec tion. The components are: (a) coronary flow distributions with appropr iate heterogeneity, (b) metabolism of the substrates for energy produc tion, (c) ATP, PCr and energy metabolism and (d) calcium metabolism as it relates to excitation-contraction coupling. The modeling should pr ovide: (1) appropriate responses to regional ischemia induced by const riction of a coronary artery, including tissue contractility loss and aneurysmal dilation of the ischemic region; (2) physiological response s to rate changes such as treppe and changes in metabolic demand and ( 3) changes in local metabolic needs secondary to changes in the site o f pacing stimulation and shortening inactivation or stretch activation of contraction. (C) 1998 Elsevier Science Ltd. All rights reserved.