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05 July 2022 : Original article  

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 2022; 27:e935338

Table 1 Experimental details of pig orthotopic heart transplants in baboons (n=4).

Baboon (weight)Pig genotype (weight)Cold ischemic time (mins)SurvivalClinical courseCause of death
B217 (8.5 kg)GTKO. hCD55 (13.0 kg)130(a)3 hoursVentricular arrhythmiasVentricular fibrillationCardiac arrest
B15416 (9.5 kg)GTKO.hCD55 (12.1 kg)63(b)3 monthsSinus tachycardia (days 0–30)Hypoxia (days 0–7)Hypertension (days 0–30)Central line infection( – day 14)Left ventricular hypertrophy (day 30)Sudden death – dysrhythmia suspected
B 1917 (8.3 kg)GTKO.hCD46. hTBM (9.9 kg)77(b)8 monthsHypoxia (days 0–7)Hypertension (days 0–90)Tachycardia (days 0–90)Increased troponin I (day 180)Sudden death (day 241)AMR and CMR
B37367 (6.0 kg)GTKO.hCD46. hTBM (6.0 kg)71(b)4 hoursHypoxia, Tachypnea, Tachycardia, Hypertension followed by hypotension, Ventricular fibrillation with resuscitationIdioventricular rhythm, cardiac arrest
(a) Stored in cold University of Wisconsin (UW) solution in ice for 60 minutes before OHTx. (b) Perfused with cold del Nido solution, and immediately transplanted. No ice storage. GTKO – α1,3-galactosyltransferase gene-knockout; hCD46 – human complement-regulatory protein CD46; hCD55 – human complement-regulatory protein CD55; hTBM – human thrombomodulin; AMR – antibody-mediated rejection; CMR – cell-mediated rejection.

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