THE IN-VIVO QUANTIFICATION 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 cont ractility in a load-independent fashion. Potentially load-insensitive measures of ventricular performance were therefore evaluated in 10 ope n- and closed-chested, anesthetized rabbits, LV transmural pressure an d myocardial segment length were measured using micromanometry and son omicrometry during steady-state and transient inferior vena caval occl usion, over a range of inotropic and loading conditions, For each inte rvention, segmental stroke work was calculated as the area within the left ventricular transmural pressure-length loops at a given end-diast olic segment length during inferior vena caval occlusion; regression a nalysis was applied to obtain the linear Frank-Starling relationship. In both open- and closed-chested states, these relationships were high ly linear (r=0.97 +/- 0.1) and reproducible. The slope of the linear r elationship between segmental stroke work and end-diastolic segment le ngth increased significantly with calcium and epinephrine infusions (P <0.05 v control) but was not significantly altered by decreased afterl oad or increased afterload (P>0.4). The x-intercept was not significan tly altered by changes in intropy or afterload (P>0.4). These data val idate the linear Frank-Starling relationship and the slope, M(W), as a load-insensitive index of contractility in the intact rabbit. This st udy presents a novel approach to the quantification of regional cardia c function in smaller animals. (C) 1996 Academic Press Limited