Classically, the heart is viewed-as consisting of two pumps in series. with the out. put of one ventricle becoming the input to the other ventricle. Thus, one ventricle could only influence the other ventricle by changing its output, thereby eventually changing the input to the other ventricle. However, the anatomical association between the ventricles suggests that a direct myocardial relationship exists. Changes in the volume or pressure of one ventricle have been shown to affect the diastolic compliance and shape of the contralateral ventricle. In isolated heart preparations, changes in the left ventricular volume and free wall integrity have been shown to alter right ventricular systolic pressure. Recent experimental studies have shown changes in left ventricular filling characteristics caused by acute changes in right ventricular volume. Experimental and clinical data suggest that ventricular interactions are also important in the pathophysiology conditions. However, the previous studies have been empirical with no direct, quantifiable measurement of ventricular interdependence. Also, a theoretical analysis or comprehensive view of ventricular interdependence is needed. To better understand diastolic ventricular interdependence, this grant proposal will develop techniques to quantify ventricular interdependence and will develop a theoretical model to explain the transfer of pressure and volume information between the ventricles. Based upon the balance of forces across the septum. four equations will be derived to explain the changes in ventricular pressure or volume caused by changing the pressure or volume of the contralateral ventricle. Using previously developed experimental techniques, this grant proposal will validate the theoretical analysis. More importantly, this grant proposal will quantify ventricular interdependence both in vivo and in vitro in the normal heart, will examine the effects of altered regional compliance on ventricular interdependence, and will determine the atrial contribution to ventricular interdependence. This grant proposal will also quantify pericardial effects on ventricular interdependence at normal and elevated levels of pericardial pressure. The information obtained in this study will provide new insight into the ventricular mechanics in normal and pathological conditions; will provide a direct means to measure changes in ventricular interdependence; and will improve the understanding of the mechanisms of ventricular interdependence.
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