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Abstract
Grant Number: 7R01HL072011-02 Project Title: Integrated Modeling of Cardiac Metabolism and Transport
PI Information: Name Title BEARD, DANIEL A. dbeard@mcw.edu ASSOCIATE PROFESSOR Abstract: DESCRIPTION (provided by applicant): The overall goal of this proposed theoretical study is to develop cardiac tissue computer modeling tools to be used for the following applications: (1) analysis of steady-state data on myoglobin saturation and oxygen distribution in isolated perfused hearts; (2) analysis of transient data on energetics metabolism and oxygen transport in cardiac tissue; and (3) design and analysis of experiments for probing signaling and control mechanisms linking metabolic and transport processes. The proposed project takes a step toward a (more) complete multi-scale description of molecular, cellular, and tissue function by focusing on the coupling between substrate transport and cellular energetics in cardiac muscle tissue. The tools that we develop will integrate state-of-the-art knowledge of the relevant pathways of metabolism and energy transduction in working cardiomyocytes, oxygen transport in cardiac muscle tissue, and microvascular blood flow in coronary capillary networks. Spectrographic measurements of myoglobin saturation in isolated perfused guinea pig hearts have prompted us to develop a transport model for oxygen in cardiac tissue to be used to analyze and interpret the experimental findings. With this model, we are beginning to make quantitative sense of the data from the isolated hearts. Next, we aim to extend this model to link to a model of distributed energy transduction. This integrated model will allow us to investigate more complex phenomena, including transient data on oxygen uptake and 31P-NMR data on cardiac energetics. Further applications of the proposed integrated model include profiling physiological responses to several challenges, such as (1) exercise; (2) ischemia; and (3) myoglobin and adenylate kinase gene deletions.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
bioenergetics, cardiovascular system, computer program /software, computer simulation, computer system design /evaluation
adenosine triphosphate, biological model, biological signal transduction, blood flow, capillary, enzyme substrate, hemodynamics, microcirculation, model design /development, muscle cell, myocardium, myoglobin, oxygen transport
animal tissue, nuclear magnetic resonance spectroscopy
Institution: MEDICAL COLLEGE OF WISCONSIN 8701 WATERTOWN PLANK RD MILWAUKEE, WI 532260509 Fiscal Year: 2004 Department: PHYSIOLOGY Project Start: 01-APR-2004 Project End: 28-FEB-2008 ICD: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE IRG: ZRG1