Thein vivoQuantification of Myocardial Performance in Rabbits: a Model for Evaluation of Cardiac Gene Therapy

Evaluating cardiac gene therapy in the intact animal requires an index of cardiac function capable of detecting regional differences in contractility in a load-independent fashion. Potentially load-insensitive measures of ventricular performance were therefore evaluated in 10 open- and closed-chested, anesthetized rabbits. LV transmural pressure and myocardial segment length were measured using micromanometry and sonomicrometry during steady-state and transient inferior vena caval occlusion, over a range of inotropic and loading conditions. For each intervention, segmental stroke work was calculated as the area within the left ventricular transmural pressure-length loops at a given end-diastolic segment length during inferior vena caval occlusion; regression analysis was applied to obtain the linear Frank–Starling relationship. In both open- and closed-chested states, these relationships were highly linear (r=0.97±0.1) and reproducible. The slope of the linear relationship between segmental stroke work and end-diastolic segment length increased significantly with calcium and epinephrine infusions (P<0.05vcontrol) but was not significantly altered by decreased afterload or increased afterload (P>0.4). The x-intercept was not significantly altered by changes in intropy or afterload (P>0.4). These data validate the linear Frank–Starling relationship and the slope, MW, as a load-insensitive index of contractility in the intact rabbit. This study presents a novel approach to the quantification of regional cardiac function in smaller animals.