Improved long-term graft survival after HO-1 induction in brain-dead donors.

Abstract

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.

• Authors: K Kotsch, M Francuski, A Pascher, R Klemz, M Seifert, J Mittler, G Schumacher, R Buelow, H-D Volk, S G Tullius, P Neuhaus, J Pratschke
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 6 Issue 3 Pg. 477-86 (Mar 2006) ISSN: 1600-6135 [Print] United States
• PMID: 16468956 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Protoporphyrins
• zinc protoporphyrin
• cobaltiprotoporphyrin
• Heme Oxygenase-1

Topics

• Animals
• Brain Death
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Follow-Up Studies
• Graft Rejection (enzymology, pathology, prevention & control)
• Graft Survival (drug effects, physiology)
• Heme Oxygenase-1 (antagonists & inhibitors, metabolism)
• Kidney Transplantation
• Prognosis
• Protoporphyrins (pharmacology)
• Rats
• Rats, Inbred F344
• Rats, Inbred Lew
• Risk Factors
• Time Factors
• Tissue Donors