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Right ventricular failure (RVF) is a major cause of mortality in pulmonary hypertension (PH) patients. Mechanical circulatory support holds promise for this population, but there are currently no clinical devices for long-term right ventricular (RV) support. Investigations into optimal device parameters and cannulation configurations for PH-induced RVF (PH-RVF) are needed. We developed and evaluated a low-profile, ventricular assist device (VAD)-quality pump combined with a low-resistance membrane oxygenator, the Pulmonary Assist Device (PAD), for RV support in 11 sheep with chronic PH and RV hypertrophy. Four central cannulation configurations were evaluated: (1) right atrium-to-left atrium (RA-LA, N=3), (2) RA-to-pulmonary artery (RA-PA, N=3), (3) pumpless PA-to-LA (PA-LA, N=2), and (4) RA-ascending aorta (RA-Ao, N=3). Acute RVF was induced, and mechanical support was provided for up to 6 hours with blood flow rates of 1-3 L/min. Circuit, hemodynamic and echocardiographic data were collected. RA-LA achieved blood flow of 3 L/min within pump's operable speed, while RA-PA and RA-Ao were flow-limited due to higher circuit afterload. PA-LA could not achieve flow above 1 L/min. The oxygenator maintained a low resistance of <4 mmHg/L/min and provided oxygen delivery of 114 mL/min. RA-LA demonstrated serial RV unloading and lower inotropic dependence with increasing circuit flow. RA-Ao exhibited some RV unloading, but to a lesser extent compared to RA-LA. Meanwhile, the hemodynamic response was highly variable in RA-PA. In one trial of RA-PA, the circuit elicited severe pulmonary hemorrhage. Based on echocardiograms, only RA-LA preserved physiologic ventricular geometry. RA-LA successfully unloads the RV at a lower pump speed, lower inotrope requirement, and improved LV filling compared to RA-Ao. RA-PA and pumpless PA-LA configurations were less viable as RV support in this study. [ABSTRACT FROM AUTHOR]