Single beat estimation of the slope of the end-systolic pressure-volume relation assumes symmetric left ventricular pressure increase and decay and requires extrapolation of peak isovolumic developed pressure (Pmax) from the left ventricular pressure curve of an ejection contraction. To test the sensitivity of this slope to positive inotropic stimuli, biplane cineangiocardiography and simultaneous high-fidelity left ventricular pressure measurements were performed in 50 patients with heart disease. The end-systolic pressure-volume relations were assessed under baseline conditions and during norepinephrine infusion (n = 19) or after postextrasystolic potentiation (n = 24), or both (n = 7). Norepinephrine did not change left ventricular end-systolic volume despite significant elevations of end-systolic pressure. Postextrasystolic potentiation significantly decreased end-systolic volume in association with an unaltered left ventricular end-systolic pressure. The potentiation significantly decreased the pressure half-time of contraction, an index of the speed of the left ventricular pressure increase, while it increased the pressure half-time of relaxation, an index of the speed of the pressure decline, indicating asymmetric pressure increase and decay. The slope of the end-systolic pressure-volume relation increased from 3.3 to 4.4 mm Hg/ml/m2 (p less than 0.001) during norepinephrine infusion. In contrast, despite an augmented contractility, the slope decreased significantly from 3.2 to 2.4 mm Hg/ml/m2 (p less than 0.0001) after the potentiation. The slope showed a high correlation with Pmax (r = 0.86, p less than 0.0001, n = 107). Thus, the slope of the end-systolic pressure-volume relation derived from single beat analysis is not always sensitive to inotropic interventions.(ABSTRACT TRUNCATED AT 250 WORDS)