Direct mechanical ventricular actuation (DMVA) is a unique, non blood contacting method for biventricular cardiac assist. Although DMVA has successfully provided cardiac assist for more than 7 days in humans, with long-term survival, its potential for long-term circulatory support has not been adequately investigated. DMVA has not been studied in the large ruminants commonly used to evaluate support devices. To develop a large animal experimental model of prolonged total circulatory support using DMVA, Suffolk sheep (n = 10) underwent sterile instrumentation for hemodynamic and chemistry monitoring. After baseline values were obtained, a left lateral thoracotomy and pericardotomy were performed. Upon electrical ventricular fibrillation (VF), DMVA was begun and the thoracotomy closed. Total circulatory support was continued until mean arterial pressure (MAP) persisted below 50% of the baseline value for more than 1 hr, with a goal of 7 days' support. Mean duration (plus or minus the standard deviation [SD]) of circulatory support was 65.9 +/- 56.8 hr (range, 10-168 hr). Pressors were not used during DMVA support. The subject supported for the maximal time (7 days) was defibrillated into sinus rhythm. No CK-MB fraction was greater than 1%, suggesting that DMVA, even with prolonged application during VF, does not result in myocardial injury. Blood urea nitrogen and creatinine levels indicate renal function was preserved. The model described represents the longest period any animal has been supported in VF using DMVA. This new model will be useful in determining what limitations, if any, exist to the prolonged use of DMVA for circulatory support.