Heme oxygenase-1 (HO-1) degrades heme into iron, biliverdin, and carbon monoxide (CO). HO-1 expression can be used therapeutically to ameliorate undesirable consequences of ischemia reperfusion injury (IRI), but the mechanism by which this occurs, remains to be established. Rat hearts, exposed to a prolonged period (24 h) of cold (4 degrees C) ischemia, failed to function upon transplantation into syngeneic recipients. Induction of HO-1 expression by administration of cobalt protoporphyrin IX (CoPPIX) to the graft donor restored graft function. Inhibition of HO-1 enzymatic activity, by administration of zinc protoporphyrin (ZnPPIX) at the time of transplantation, reversed the protective effect of HO-1. Exposure of the graft donor as well as the graft (during ischemia) to exogenous CO mimicked the protective effect of HO-1. This was associated with a significant reduction in the number of cells undergoing apoptosis in the graft with no apparent decrease of intravascular fibrin polymerization, platelet aggregation, or P-selectin expression. In conclusion, HO-1-derived CO prevents IRI associated with cardiac transplantation based on its antiapoptotic action. The observation that exposure of the donor and the graft to CO is sufficient to afford this protective effect should have important clinical implications in terms of preventing IRI associated with heart transplantation in humans.

No abstract

ATG induction was associated with an improved (but n.s.) trend in patient and graft survival. Patients induced with ATG had a higher rate of CMV infections and haematological complications.

Because PRA-STAT is very reproducible, detects both HLA class I and II antibodies, and is not influenced by rejection therapy, we consider it an additional tool for pre- and posttransplant monitoring of kidney allograft recipients.

We evaluated survival and renal function of cadaveric donor grafts according to donor age. The median age of the pediatric donors was 7.0 (0.7-16) years in 46 patients [median age 11.8 years (range) 3-16.8 years]. The median age of the adult donors was 34.4 (19-54) years in 59 patients [median age 12.1 years (range) 7-17.3 years]. Thirty patients were treated with azathioprine and prednisolone and 75 with cyclosporine A and prednisolone. The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were determined by the clearances of 51chromium-EDTA and 125iodine-hippurate 1-48 months after kidney transplantation. There was no difference in graft survival between pediatric and adult grafts. There were also no differences in GFR in patients receiving grafts from pediatric or adult donors; 2-3 months after transplantation the GFR in recipients of pediatric grafts was 62 +/- 20 ml/min per 1.73 m2 compared with 61 +/- 21 in those receiving adult grafts. The ERPF in recipients of adult grafts was significantly higher in the 1st month after transplantation: 486 +/- 239 versus 362 +/- 158 ml/min per 1.73 m2. From the 4th to the 6th month after transplantation this difference disappeared: the ERPF of grafts from pediatric donors was 279 +/- 131 ml/min per 1.73 m2 compared with 273 +/- 123 ml/min per 1.73 m2 in grafts from adult donors. Using the single-kidney GFR and ERPF on an age-matched group of probands with minor diseases as references, 2-3 months after transplant the mean GFR of grafts from pediatric donors increased to 118% +/- 51%, whereas the GFR of adult donor grafts fell to 60% +/- 22% over the same period. After 4-6 months the ERPF in pediatric grafts was 96% +/- 55% compared with 50% +/- 22% in adult grafts. We conclude that graft survival and function in children with either a pediatric or an adult graft may not differ because graft function adapts to the requirement of the recipient.