Acute right ventricular (RV) pressure overload may be caused by pulmonary embolism, hypoxic pulmonary vasoconstriction, left ventricular failure, or following cardiac transplantation or prolonged cardiopulmonary bypass. RV pressure overload may result in RV failure or dysfunction, and is a major cause of morbidity and mortality in these conditions. Preliminary studies by the applicant have demonstrated that RV systolic function remains depressed even after restoration of normal loading conditions. Recent evidence suggests that passive mechanical factors, such as myocardial creep, as well as active contractile processes, may contribute to systolic function following acute RV pressure overload. If disruption of collagen architecture contributes to RV dysfunction after pressure overload, then therapies directed at preserving the integrity of the extracellular matrix may provide a therapeutic modality complementary to inotropic stimulation in acute RV failure. Quantitative assessment of regional RV systolic function will be performed using pressure-segment length loop analysis in an open-chest pig model of RV pressure and volume overload. Histologic and ultrastructural measurements of collagen architecture will e performed using optical and electron microscopy following perfusion-fixation of hearts. The histologic and ultrastructural measurements will then be related to changes in derived indices of ventricular function, to determine whether specific changes in collagen architecture cause predictable changes in ventricular function.
