There is a very high incidence of heart failure in this country -- particularly, failure manifest as impairments in ventricular relaxation, impairments of filling, and decreased ventricular compliance. In consideration of this, successful efforts to extend the concept of ventriculo-vascular coupling to the filling side of the heart (a concept which has been so productive with respect to ejection, i.e., systolic interaction) would represent direct advancements toward the elucidation of mechanisms by which the filling ventricle interacts with the vascular load during health and failure. This is crucially important since it is the nature of this dynamic interaction that will determine the extent of ventricular filling versus regurgitation into the venous vascular system. Although characterization of ventricular dynamic properties during filling has been fairly successful, there is presently no complete quantitative representation of vascular load at the veno-atrio-ventricular junction sufficient to enable prediction of the instantaneous pulmonary venous flow response to dynamic changes in left atrial pressure. The overall goal of this project is to identify linear and nonlinear dynamic properties of the pulmonary venous system to better understand how the venous vascular load interacts with the left ventricle to determine filling during failure. A major specific aim is to determine a linear systems representation of pulmonary venous dynamic pressure-flow characteristics. Preliminary data indicates that the """"""""white-noise approach"""""""" to admittance determination in conjunction with multiple-input multiple-output systems analysis techniques make it possible with few assumptions to overcome difficulties in this regard that may have defused the enthusiasm of previous investigators: low-amplitude venous pulsations, inaccurate flow determination, and low-frequency contamination from the pulmonary arterial port. Another specific aim is to characterize nonlinearities (in dynamic pressure-flow characteristics) that are expected to exist in the pulmonary vascular bed. If in the """"""""white-noise"""""""" approach for linear identification the input sequence of pressure perturbations is not only """"""""white"""""""" but also """"""""Gaussian"""""""", then the extent and nature of the nonlinearities can be identified. As a final specific aim, a computer simulation of a quantitative model derived from the analysis of biological data will be evaluated in terms of its predictive and explanative validity. The model will then be incorporated in iterative modifications of experimental protocol in order to optimize animal usage as well as identify parameters that sensitively affect ventriculo-vascular interaction during filling in health and LV failure.
