In the recently published clinical study (UNLOAD), sodium nitroprusside (NTP) improved cardiac function in patients with severe aortic stenosis (AS) and left ventricular (LV) systolic dysfunction. We explored possible mechanisms of these findings using a series of numerical simulations. A closed-loop lumped parameters model that consists of 24 differential equations relating pressure and flow throughout the circulation was used to analyze the effects of varying hemodynamic conditions in AS. Hemodynamic data from UNLOAD study subjects were used to construct the initial simulation. Systemic vascular resistance, heart rate and aortic valve area were directly entered into the model while end-systolic and diastolic pressure-volume (PV) relationships were adjusted using previously published data to match modeled and observed end-systolic and end-diastolic pressures and volumes. Initial simulation of NTP treatment by reduction of SVR was not adequate. In order to obtain realistic model hemodynamics that reliably reproduce NTP treatment effects, we performed a series of simulations while simultaneously changing end-systolic elastance (E_es), end-systolic volume at zero pressure (V₀), and diastolic pressure volume shift. Our data indicate that either E_es increase or V₀ decrease is necessary to obtain realistic model hemodynamics. In 5 patients, we corroborated our findings by using the model to duplicate individual PV loops obtained before and during NTP treatment. In conclusion, using a numerical model, we identified ventricular function parameters that are responsible of improved hemodynamics during NTP infusion in AS with LV dysfunction.