Reduction of consumptive coagulopathy using porcine cytomegalovirus-free cardiac porcine grafts in pig-to-primate xenotransplantation.
BACKGROUND
Xenotransplantation using pigs as the source species for organs carries a potential risk for transmission and activation of porcine herpesviruses. Activation of porcine cytomegalovirus (PCMV) in pig-to-baboon xenotransplantation is associated with xenograft injury and possibly an increased incidence of consumptive coagulopathy (CC).


METHODS
To further investigate the role of PCMV activation in the occurrence of CC, a strategy to exclude PCMV from the donor was developed. To exclude PCMV, piglets were early-weaned and raised separated from other swine. These piglets were used as donors in an experimental protocol of pig-to-baboon heart xenotransplantation.


RESULTS
Early weaning of piglets was successful in excluding PCMV. Use of PCMV-free cardiac porcine xenografts in baboons resulted in prolonged graft survival and prevented consumptive coagulopathy in all recipients.


CONCLUSIONS
The use of PCMV-free cardiac grafts is beneficial in reducing the direct effects of PCMV activation in the graft (tissue damage) and the indirect effects of PCMV activation in the recipient (consumptive coagulopathy).
Mueller
Nicolas J
NJ
Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRJ 504, Boston, MA 02114, USA. jfisherman@partners.org
Kuwaki
Kenji
K
Dor
Frank J M F
FJ
Knosalla
Christoph
C
Gollackner
Bernd
B
Wilkinson
Robert A
RA
Sachs
David H
DH
Cooper
David K C
DK
Fishman
Jay A
JA
D000818:Animals; D001483:Base Sequence; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification*; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics; D004211:Disseminated Intravascular Coagulation / Q000517:prevention & control*; D005340:Fibrinogen / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology; D016027:Heart Transplantation / Q000009:adverse effects / Q000502:physiology*; D010215:Papio; D010976:Platelet Count; D016133:Polymerase Chain Reaction; D013552:Swine; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000502:physiology*
D017931:DNA Primers; D004279:DNA, Viral; D005340:Fibrinogen