Irradiation before and donor splenocyte infusion immediately after transplantation induce tolerance to lung, but not heart allografts in miniature swine.

Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four and left-sided lung transplantation (LTX) in seven minipigs from gender- and SLA-mismatched donors. All recipients received nonmyeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, and three further animals rejected 119, 239 and 360 days post-transplantation. In both groups, peripheral blood donor leucocyte chimerism peaked 1 h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of passenger leucocyte chimerism.

Two axial-flow Synergy Micro-Pumps as a biventricular assist device in an ovine animal model.

OBJECTIVE: This study investigated the use of 2 Synergy Micro-Pumps for full biventricular assist device (BiVAD) support. We examined right-sided and left-sided hemodynamic parameters over a range of right-sided and left-sided pump speeds in an acute, fibrillating, non-beating-heart model in sheep. METHODS: Five juvenile sheep (43 ± 2 kg) were implanted with two Synergy Micro-Pumps (CircuLite Inc, Saddle Brook, NJ), 1 in the right (RV) and 1 in the left ventricle (LV), through a median sternotomy. The RVAD outflow graft was anastomosed end-to-side to the pulmonary artery and the LVAD outflow to the ascending aorta. After surgical implantation of both pumps, ventricular fibrillation was induced and hemodynamic parameters were measured at 9 different levels of RVAD pump speed (from 20,000 to 28,000 rpm at 1,000-rpm increments), while the speed of the LVAD was set constant at 24,000, then at 26,000, and finally, at 28,000 rpm. RESULTS: At a fixed LVAD speed, RVAD and LVAD flow both increased identically as RVAD speed was increased. This was due to redistribution of blood volumes that resulted in resetting of pressure gradients across each pump and each vascular bed in a manner dictated by the pump pressure-flow characteristics. Results were similar with LVAD set at 24,000, 26,000, or 28,000 rpm. At the highest LVAD and RVAD speeds, flow averaged 3.1 ± 0.7 liters/min, and pressures in the right atrium, pulmonary artery, left atrium, and aorta averaged 2.2 ± 3.7, 24.4 ± 6.5, 22.4 ± 5.5, and 56.6 ± 8.5 mm Hg, respectively. CONCLUSION: BiVAD support with the 2 Synergy Micro-Pumps is feasible and able to provide full hemodynamic support in sheep. This approach holds promise for providing biventricular partial support in humans and, in particular, for full support in small adults and children.