PMID- 34820778
OWN - NLM
STAT- MEDLINE
DCOM- 20220616
LR  - 20220808
IS  - 1869-4098 (Electronic)
IS  - 1869-408X (Print)
IS  - 1869-408X (Linking)
VI  - 13
IP  - 3
DP  - 2022 Jun
TI  - Biological Equivalence of GGTA-1 Glycosyltransferase Knockout and Standard 
      Porcine Pericardial Tissue Using 90-Day Mitral Valve Implantation in Adolescent 
      Sheep.
PG  - 363-372
LID - 10.1007/s13239-021-00585-0 [doi]
AB  - OBJECTIVE: There is growing interest in the application of genetically engineered 
      reduced antigenicity animal tissue for manufacture of bioprosthetic heart valves 
      (BHVs) to reduce antibody induced tissue calcification and accelerated structural 
      valve degeneration (SVD). This study tested biological equivalence of valves made 
      from Gal-knockout (GalKO) and standard porcine pericardium after 90-day mitral 
      valve implantation in sheep. METHODS: GalKO (n = 5) and standard (n = 5) porcine 
      pericardial BHVs were implanted in a randomized and blind fashion into sheep for 
      90-days. Valve haemodynamic function was measured at 30-day intervals. After 
      explantation, valves were examined for pannus, vegetation, inflammation, 
      thrombus, and tissue calcification. RESULTS: Nine of 10 recipients completed the 
      study. There was no difference between study groups for haemodynamic performance 
      and no adverse valve-related events. Explanted BHVs showed mild pannus 
      integration and minimal thrombus, with no difference between the groups. Limited 
      focal mineral deposits were detected by x-ray. Atomic spectroscopy analysis 
      detected tissue calcium levels of 1.0 microg/mg +/- 0.2 for GalKO BHVs and 1.9 microg/mg +/- 
      0.9 for standard tissue BHVs (p = 0.4), considered to be both low and equivalent. 
      CONCLUSIONS: This is the first demonstration of biological equivalence between 
      GalKO and standard pig pericardium. The GalKO mutation causes neither intrinsic 
      detrimental biological nor functional impact on BHV performance. Commercial 
      adaptation of GalKO tissue for surgical or transcatheter BHVs would remove the 
      clinical disparity between patients producing anti-Gal antibody and BHVs 
      containing the Gal antigen. GalKO BHVs may reduce accelerated tissue 
      calcification and SVD, enhancing patient choices, especially for younger 
      patients.
CI  - (c) 2021. The Author(s).
FAU - McGregor, Christopher
AU  - McGregor C
AD  - Institute of Cardiovascular Science, University College London, London, UK. 
      mcgre256@umn.edu.
AD  - Department of Surgery, University of Minnesota, 8195B, MMC 195 Mayo, Minneapolis, 
      MN, 55455, USA. mcgre256@umn.edu.
FAU - Salmonsmith, Jacob
AU  - Salmonsmith J
AD  - Department of Surgery, University of Minnesota, 8195B, MMC 195 Mayo, Minneapolis, 
      MN, 55455, USA.
AD  - Department of Mechanical Engineering, University College London, London, UK.
FAU - Burriesci, Gaetano
AU  - Burriesci G
AD  - Department of Mechanical Engineering, University College London, London, UK.
AD  - Ri.MED Foundation, Bioengineering Group, Palermo, Italy.
FAU - Byrne, Guerard
AU  - Byrne G
AD  - Institute of Cardiovascular Science, University College London, London, UK.
AD  - Department of Surgery, University of Minnesota, 8195B, MMC 195 Mayo, Minneapolis, 
      MN, 55455, USA.
LA  - eng
GR  - MR/R006393/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/L005891/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211124
PL  - United States
TA  - Cardiovasc Eng Technol
JT  - Cardiovascular engineering and technology
JID - 101531846
RN  - EC 2.4.- (Glycosyltransferases)
SB  - IM
MH  - Animals
MH  - *Bioprosthesis/adverse effects
MH  - *Calcinosis
MH  - Glycosyltransferases
MH  - *Heart Valve Prosthesis
MH  - Humans
MH  - Mitral Valve/surgery
MH  - Pericardium/transplantation
MH  - Sheep
MH  - Swine
PMC - PMC9197892
OTO - NOTNLM
OT  - Biological heart valve
OT  - Gal knockout
OT  - Tissue equivalency
OT  - Xenogeneic antigens
EDAT- 2021/11/26 06:00
MHDA- 2022/06/18 06:00
PMCR- 2021/11/24
CRDT- 2021/11/25 06:47
PHST- 2021/05/11 00:00 [received]
PHST- 2021/10/19 00:00 [accepted]
PHST- 2021/11/26 06:00 [pubmed]
PHST- 2022/06/18 06:00 [medline]
PHST- 2021/11/25 06:47 [entrez]
PHST- 2021/11/24 00:00 [pmc-release]
AID - 10.1007/s13239-021-00585-0 [pii]
AID - 585 [pii]
AID - 10.1007/s13239-021-00585-0 [doi]
PST - ppublish
SO  - Cardiovasc Eng Technol. 2022 Jun;13(3):363-372. doi: 10.1007/s13239-021-00585-0. 
      Epub 2021 Nov 24.