Improved long-term graft survival after HO-1 induction in brain-dead donors.
Brain death (BD) of the donor, a risk factor uniquely relevant for organs derived from cadaver donors, influences organ quality by induction of various inflammatory events. Consequently ischemia/reperfusion injury is deteriorated and acute and chronic rejections accelerated. Donor treatment might be an approach to improve the quality of the graft. The induction of heme oxygenase 1 (HO-1) has been shown to exert beneficial effects in living-donor transplantation models. Therefore, we examined the impact of donor treatment with the selective inducer of HO-1, cobalt protoporphyrin (CoPP), on organ quality and transplant outcome in a standardized BD model in a F344-->LEW kidney transplant rat model. Immediately after BD induction, donor animals were administered a single dose of CoPP (5 mg/kg) and in control groups, HO-1 activity was blocked with zinc protoporphyrin (ZnPP, 20 mg/kg). Recipients of organs from brain-dead donors treated with CoPP survived significantly better than those from untreated brain-dead donors (p < 0.05) and intra-graft analysis showed improved histology (p < 0.05). Blockade of HO-1 with ZnPP decreased the survival rates (p < 0.05) comparable to untreated brain-dead donors. Our results demonstrate that HO-1 induction by one single treatment of CoPP in brain-dead donors leads to enhanced allograft survival.
Institute of Medical Immunology, Universitätsmedizin Charité Campus Mitte, Schumannstrasse 20/21, 10117 Berlin, Germany.
K
K
Kotsch
M
M
Francuski
A
A
Pascher
R
R
Klemz
M
M
Seifert
J
J
Mittler
G
G
Schumacher
R
R
Buelow
H-D
HD
Volk
S G
SG
Tullius
P
P
Neuhaus
J
J
Pratschke
D000818:Animals; D001926:Brain Death; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016030:Kidney Transplantation; D011379:Prognosis; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012307:Risk Factors; D013997:Time Factors; D014019:Tissue Donors
D004791:Enzyme Inhibitors; D011524:Protoporphyrins; C017803:zinc protoporphyrin; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1