The diastolic function of the heart has interested physiologists and clinicians for many years. In the normal state, the manner in which the heart fills influences beat-to-beat changes in stroke volume and respiratory variation in cardiac function. In pathologic conditions, abnormalities of diastolic function are common, and contribute toward pulmonary venous hypertension. The purpose of the proposed research is to provide a clearer understanding of certain factors which influence the relation between filling pressure and volume in the intact heart in the dog, primarily in the quasi-normal state. Five hypotheses (along with sub-hypotheses) will be tested, three relating to external influences on filling and two to properties of the myocardium which influence filling. In project 1 the hypothesis that pericardial restraint to filling is more important for the right than the left ventricle will be tested by measuring ventricular dimensions (sonomicrometry) over a wide range of filling pressures before and after pericardiectomy. Relative alterations in the diastolic pressure-dimension relation after pericardiectomy will be analyzed to compare the two chambers. In project 2, the hypothesis that pericardial """"""""contact"""""""" pressure varies by region over the surface of the heart will be tested. Low-profile balloons will be used to measure regional pericardial pressure. In project 3 a number of hypotheses having to do with the influence of the cardiac fossa (i.e., the lungs within the intact thoracic cavity) on cardiac filling will be tested. These hypotheses stem from a recent observation which indicates that the cardiac fossa influences the relation between right and left heart transmural filling pressures. To test these hypotheses, cardiac dimensions and pressures will be measured with the chest closed and then widely opened. In project 4 the hypothesis that the beating left ventricle is not passive, even during """"""""diastatic"""""""" portions of the filling cycle, will be tested. Here, pressure-dimension relations obtained in the beating heart will be compared to those obtained in the freshly arrested left ventricle. In project 5, the hypothesis that the mechanics of contraction influence peak left ventricular lengthening/filling rates will be tested. Left ventricular dimensions and volumes (impedance catheter) will be measured during transient, non-steady state alterations in loading conditions in order to determine the influence of end-systolic dimension/volume, extent of shortening and timing of load changes on peak lengthening/filling rates.
