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08 June 2022 : Original article  

[In Press] Cardiac and Pulmonary Histopathology in Baboons Following Genetically-Engineered Pig Orthotopic Heart Transplantation

Silvio H. Litovsky1BDE, Jeremy B. Foote2BCDE, Abhijit Jagdale3BE, Gregory Walcott4BE, Hayato Iwase3BDE, Mohamed H. Bikhet3BDE, Takayuki Yamamoto3BE, Christophe Hansen-Estruch3BE, Mohamed B. Ezzelarab5BE, David Ayares6AE, Waldemar F. Carlo7BE, Leslie A. Rhodes7BE, Jack H. Crawford8BE, Santiago Borasino8BE, Robert J. Dabal8BE, Luz A. Padilla8BE, Hidetaka Hara3BE, David K.C. Cooper3ABDEFG, David C. Cleveland8ABDEFG

DOI: 10.12659/AOT.935338

Ann Transplant In Press; DOI: 10.12659/AOT.935338  

Available online: 2022-06-08, In Press, Corrected Proof

Publication in the "In-Press" formula aims at speeding up the public availability of the pending manuscript while waiting for the final publication. The assigned DOI number is active and citable. The availability of the article in the Medline, PubMed and PMC databases as well as Web of Science will be obtained after the final publication according to the journal schedule


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.
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.
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).
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.

Keywords: Baboon; Heart Transplantation; Lungs; Pig; Xenotransplantation


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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358