This project is a continuation of applicant's work to apply concepts from engineering and physics to better define the determinants of cardiac function in the intact beating heart. Dog experiments would be combined with theoretical analysis to define the relative importance of these determinants during both diastole and systole as the heart adapts to mechanical changes. The project has four Specific Aims.1) To test the hypothesis that the upward shift in the left ventricular diastolic pressure-volume curve results from a combination of slowed relaxation (early diastole) and stretch activation of the ischemic myocardium (late diastole). 2) To measure experimentally the quantitative roles of the proposed determinants of filling, including: passive myocardial elasticity, ventricular interaction, the pericardium and lungs, active relaxation, and stretch activation, with particular emphasis on early diastole and the rapid filling phase. 3) To continue to develop and validate experimentally a deterministic model of ventricular interaction that explicitly considers the effect of right ventricular output and the transit time through the lungs as well as the lungs' mechanical infringement on the heart. 4) To use the data gathered in Specific Aims 1 and 2 to develop and validate a mathematical model of the entire diastolic period and could account for the effects of ischemia or calcium channel blockers, which change passive elasticity and ventricular interaction as well as active relaxation and stretch activation of the myocardium.
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