Pressure-volume analysis as a method for quantifying simultaneous drug (amrinone) effects on arterial load and contractile state in vivo

Pressure-volume relation analysis was used to independently quantify changes in ventricular contractile performance and vascular loading in intact anesthetized dogs before and after a single bolus of intravenous amrinone. Ventricular systolic property changes were characterized by the end-systolic elastance (Ees = slope of the end-systolic pressure-volume relation) and arterial properties by the effective arterial elastance (Ea = end-systolic pressure/stroke volume ratio). Pressure-volume data were obtained by the conductance catheter technique with loading varied by transient inferior vena cava occlusion. Amrinone induced a 27% increase in ejection fraction at 10 min (from 44% to 56%) as a result of both a significant rise in contractility (mean Ees 4 ± 2 to 6± 3 mm Hg/ml, p < 0.001) and simultaneous reduction in arterial loading (Ea reduction from 6 ± 2 mm Hg/ml to 5 mm Hg/ml, p < 0.001). Over the subsequent 30 min, Ea revealed a significant recovery toward baseline, whereas Ees was less altered. Mean percent changes (%Δ) in both variables were linearly correlated: %ΔEa = -1.6 × %ΔEes + 3.1, r = 0.96, p < 0.001. In addition to separating ventricular from vascular property changes, the pressure-volume coupling framework was used to predict net pump performance (ejection fraction). Model predictions showed good agreement with experimental data. Thus, pressure-volume relations can be used to separately quantitate simultaneous changes in ventricular and vascular loading properties in vivo produced by pharmacologic agents with complex actions. Use of this approach in drug testing in humans should simplify data interpretation regarding mechanisms of action in specific clinical settings.