Hypotension has been the most frequently reported adverse reaction associated with infusion of the beta 1-adrenergic receptor antagonist esmolol. In some patients, this hypotension has apparently occurred independent of reduction in heart rate or systemic vascular resistance, suggesting decreased stroke volume. In the present study, the preload recuitable stroke work area (PRSWA) model was used to evaluate the negative inotropic effects of esmolol in nine chronically instrumented awake dogs. Left ventricular (LV) transmural pressure and minor axis diameter were measured by micromanometers and sonomicrometry, respectively. Vena caval occlusions were performed so that an analog of stroke work (area within LV transmural pressure-diameter loop) could be measured over a range of preloading conditions during esmolol infusions of 0, 100, 300, 1000, and 3000 micrograms/kg-1.min-1 (n = 9), and at 15 and 30 min after termination of esmolol (n = 8). The linear relationship between stroke work and end-diastolic diameter was characterized for each caval occlusion by a slope and x-intercept. PRSWA was calculated for each caval occlusion as slope/two times the square of the difference between x-intercept and the largest end diastolic diameter observed in the study of a particular dog. Heart rate was different from control (91 +/- 4) only at the highest esmolol dose (127 +/- 4). LV peak positive dP/dt, minor axis ejection shortening, stroke work, and PRSWA were depressed from control at esmolol doses greater than or equal to 300 micrograms.kg-1.min-1. All parameters except dP/dt recovered within 30 min following termination of esmolol.(ABSTRACT TRUNCATED AT 250 WORDS)