Pig Orthotopic Heart Transplantation (ohtx) in Baboons: Is an Acute Pulmonary Inflammatory Response the Key Problem?

A. Jagdale¹, D. Cleveland², M. Bikhet¹, J. Foote³, G. Walcott⁴, H. Iwase¹, T. Yamamoto¹, H. Hara¹, C. Hansens-Estruch¹, D. Ayares⁵, S. Litovsky⁶, L. Rhodes², W. Carlo⁷, J. Crawford², R. Dabal², S. Borasino², D. Cooper¹

¹Surgery, University of Alabama at Birmingham, Birmingham, AL, ²Cardiothoracic Surgery, Children's of Alabama, Birmingham, AL, ³Medicine and Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, AL, ⁴Medicine, University of Alabama at Birmingham, Birmingham, AL, ⁵Surgery, Revivicor, Blacksburg, VA, ⁶Pathology, University of Alabama at Birmingham, Birmingham, AL, ⁷Division of Pediatric Cardiology, Department of Pediatrics, University of Alabama at Birmingham, Children's of Alabama, Birmingham, AL

Meeting: 2021 American Transplant Congress

Abstract number: 347

Keywords: Heart, Heart preservation, N/A, Outcome

Topic: Basic Science » Xenotransplantation

Session Information

Session Name: Xenotranplantation and Preclinical Studies

Session Type: Rapid Fire Oral Abstract

Date: Tuesday, June 8, 2021

Session Time: 6:00pm-7:00pm

Presentation Time: 6:25pm-6:30pm

Location: Virtual

*Purpose: To investigate the mechanism of early cardio-pulmonary dysfunction after genetically engineered pig OHTx in baboons.

*Methods: OHTx from pigs expressing different genetic modifications, α‐galactosyltransferase knockout with human CD55 (GTKO/hCD55) [n=2]; α‐galactosyltransferase knockout with human CD46 and human thrombomodulin (GTKO/hCD46/hTBM) [n=2] was carried out in 4 baboons. The immunosuppressive regimen included induction with ATG (Thymoglobulin), anti-CD20mAb (Rituximab), and cobra venom factor or a C1-esterase inhibitor, and maintenance with an anti-CD40mAb, rapamycin, and low-dose steroids.

*Results: Four baboons (<12 kg) underwent orthotopic cardiac transplant of a genetically engineered pig xenograft. All four successfully emerged from cardio-pulmonary bypass. Two baboons were euthanized a few hours after OHTx while the other 2 baboons survived 3 and 8 months, respectively. Features of pulmonary dysfunction in the early post-operative period (e.g., tachypnea, reduced pO₂, reduced sO₂ etc.), particularly in the 24 hours following weaning from the ventilator, developed in all 4 baboons. The 2 baboons that were euthanized showed very high levels of IL-6, IL-8, and IFN-γ compared to the 2 that survived longer, suggesting a possible association between cytokine storm and acute pulmonary injury. Histopathological examination confirmed inflammatory lung injury in 3 baboons, including the 3-month survivor (that died from a dysrhythmia).

*Conclusions: After pig OHTx in baboons, all of our baboons experienced acute pulmonary dysfunction. Because pulmonary dysfunction can lead to impaired cardiac graft function, further research is indicated regarding the role of cytokine storm in acute pulmonary dysfunction particularly since treatment with IL-6 blockade or dexamethsone can attenuate this cytokine response.

To cite this abstract in AMA style:

Jagdale A, Cleveland D, Bikhet M, Foote J, Walcott G, Iwase H, Yamamoto T, Hara H, Hansens-Estruch C, Ayares D, Litovsky S, Rhodes L, Carlo W, Crawford J, Dabal R, Borasino S, Cooper D. Pig Orthotopic Heart Transplantation (ohtx) in Baboons: Is an Acute Pulmonary Inflammatory Response the Key Problem? [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/pig-orthotopic-heart-transplantation-ohtx-in-baboons-is-an-acute-pulmonary-inflammatory-response-the-key-problem/. Accessed November 21, 2024.

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