Doppler echocardiographic indexes of ventricular inflow have been used clinically to characterize left ventricular (LV) diastolic function. The reliability of these indexes as markers for intrinsic myocardial diastolic properties has been questioned. Micro-manometer left atrial (LA) and LV pressures as well as transmitral Doppler flow velocity signals and M-mode and 2-dimensional echocardiograms were simultaneously recorded. These unique measurements were acquired in patients with dilated cardiomyopathy under baseline conditions and during infusion of high dose amrinone. The response to amrinone was chosen as a hemodynamic model because this drug has previously been described as having beneficial effects on overall LV systolic and diastolic performance. At peak amrinone effect, LV contractility increased (as assessed using load independent end-systolic indexes) and early diastolic relaxation improved whereas passive chamber stiffness, heart rate and stroke volume were unchanged. There was a significant decrease in LV end-diastolic pressure as well as a parallel downward shift of the entire LV diastolic pressure-dimension relation. These findings, which indicated an improvement in overall LV diastolic properties, probably represent the combination of more rapid early diastolic relaxation in conjunction with a reduction in venous return, the relief of pericardial restraint or the reduction in right ventricular-LV interaction. In contrast, the ratios of Doppler-determined peak transmitral early-to-late flow velocities and early-to-late diastolic flow velocity integrals decreased with amrinone infusion, thereby suggesting a drug-induced decrease in LV diastolic compliance. Thus, in patients with idiopathic dilated cardiomyopathy, administration of amrinone has a complex effect on LV diastolic properties.(ABSTRACT TRUNCATED AT 250 WORDS)