True positive inotropy of enoximone is hard to prove clinically. It could increase the risk of myocardial ischemia when used in coronary artery disease (CAD). The analysis of the end-systolic pressure-volume relationship (ESPVR) as a load-independent parameter of the contractile left ventricular function (LVF) allows for differentiation of enoximone's unloading effects. Therefore, we analyzed ESPVR and LVF in 12 of 18 CAD patients before and after enoximone, 0.75 mg/kg intravenously. The slope k increased (seven patients) and loops of the ESPVR (12 patients) moved leftward with the enoximone an average of 32% and downward 19%, in the diastolic portion. The delta percent changes in enoximone versus control (18 patients) indicated an improved LVF via load changes: LV filling pressure fell by 50% and end-systolic volume by 28%, while dp/dt max rose by 25%, LV work by 10%, and ejection fraction by 11%. Lastly, the pacing-induced myocardial ischemia threshold increased from an average of 58 +/- 18 sec to 89 +/- 12 sec after eximone, while ischemic postpacing LV filling pressure and ST-segment changes normalized under the drug's influence. Thus, enoximone improved LVF, both by unloading and by true positive inotropy. Lack of enoximone-induced angina and an increased anginal threshold indicate that the drug can be used safely in CAD patients as well.