A novel physiological cardiac assist device (PCAD), otherwise known as the LEVRAM assist device, which is synchronized with the heartbeat, was developed to assist the left ventricle (LV) in chronic heart failure (CHF). The PCAD utilizes a single cannula, which is inserted in less than 15 s through the apex of the beating LV by means of a specially designed device. Blood is withdrawn from the LV into the PCAD in diastole and is injected back to the LV, through the same cannula, during the systolic ejection phase, thereby augmenting stroke volume (SV) and stroke work (SW). CHF with dilated LV was induced in sheep by successive intracoronary injections of 100-microm beads. The sheep (92.2 +/- 25.9 kg, n = 5) developed stable CHF with increased LV end-diastolic diameter (69.4 +/- 3.3 mm) and end-diastolic volume (LVEDV = 239 +/- 32 mL), with severely reduced ejection fraction (23.8 +/- 7.6%), as well as mild-to-moderate mitral regurgitation. The sheep were anesthetized, and the heart was exposed by left thoracotomy. Pressure was measured in the LV and aorta (Millar). The SV was measured by flow meters and the LV volume by sonocrystals. Assist was provided every 10 regular beats, and the assisted beats were compared with the preceding unassisted beats, at the same LVEDV. The PCAD displaced 13.6 +/- 3.4 mL, less than 8% of LVEDV. Added SW was calculated from the assisted and control pressure-volume loops. The efficiency, defined as an increase in SW divided by the mechanical work of the PCAD, was 85.4 +/- 16.9%. We conclude that the PCAD, working with a small displaced blood volume in synchrony with the heartbeat, efficiently augments the SW of the dilated failing LV. The PCAD is suggested for use as a permanent implantable device in CHF.