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05 July 2022: Original Paper

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

Silvio H. Litovsky 1BDE , Jeremy B. Foote 2BCDE , Abhijit Jagdale 3BE , Gregory Walcott 4BE , Hayato Iwase 3BDE , Mohamed H. Bikhet 3BDE , Takayuki Yamamoto 3BE , Christophe Hansen-Estruch 3BE , Mohamed B. Ezzelarab 5BE , David Ayares 6AE , Waldemar F. Carlo 7BE , Leslie A. Rhodes 7BE , Jack H. Crawford 8BE , Santiago Borasino 8BE , Robert J. Dabal 8BE , Luz A. Padilla 8BE , Hidetaka Hara 3BE , David K.C. Cooper 3ABDEFG* , David C. Cleveland 8ABDEFG

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