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...

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Bibliographic Details
Published in:American journal of transplantation 2006-03, Vol.6 (3), p.477-486
Main Authors: Kotsch, K., Francuski, M., Pascher, A., Klemz, R., Seifert, M., Mittler, J., Schumacher, G., Buelow, R., Volk, H.‐D., Tullius, S.G., Neuhaus, P., Pratschke, J.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain Death
Disease Models, Animal
Enzyme Inhibitors - pharmacology
Follow-Up Studies
Graft Rejection - enzymology
Graft Rejection - pathology
Graft Rejection - prevention & control
Graft Survival - drug effects
Graft Survival - physiology
heme oxygenase
Heme Oxygenase-1 - antagonists & inhibitors
Heme Oxygenase-1 - metabolism
Kidney Transplantation
Medical sciences
Prognosis
Protoporphyrins - pharmacology
Rats
Rats, Inbred F344
Rats, Inbred Lew
Risk Factors
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the urinary system
Time Factors
Tissue Donors
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Summary: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.
ISSN:1600-6135
1600-6143
DOI:10.1111/j.1600-6143.2005.01208.x