Cardiac and Pulmonary Histopathology in Baboons Following Genetically-Engineered Pig Orthotopic Heart Transplantation

BACKGROUND: Although improving, survival after pig orthotopic heart transplantation (OHTx) in baboons has been mixed and largely poor. The causes for the high incidence of early failure remain uncertain. MATERIAL/METHODS: We have carried out pig OHTx in 4 baboons. Two died or were euthanized within hours, and 2 survived for 3 and 8 months, respectively. There was evidence of a significant ‘cytokine storm’ in the immediate post-OHTx period with the elevations in IL-6 correlating closely with the final outcome. RESULTS: All 4 baboons demonstrated features suggestive of respiratory dysfunction, including increased airway resistance, hypoxia, and tachypnea. Histopathological observations of pulmonary infiltration by neutrophils and, notably, eosinophils within vessels and in the perivascular and peribronchiolar space, with minimal cardiac pathology, suggested a role for early lung acute inflammation. In one, features suggestive of transfusion-related acute lung injury were present. The 2 longer-term survivors died of (i) a cardiac dysrhythmia with cellular infiltration around the conducting tissue (at 3 months), and (ii) mixed cellular and antibody-mediated rejection (at 8 months). CONCLUSIONS: These initial findings indicate a potential role of acute lung injury early after OHTx. If this response can be prevented, increased survival may result, providing an opportunity to evaluate the factors affecting long-term survival.