title: Decreasing ratios of phosphocreatine to beta-ATP correlates to progressive acute rejection in a concordant mouse heart to rat xenotransplantation model.
abstract: Biopsies are difficult to perform in rodent heart transplant models without compromising the graft function and therefore other means to evaluate the grafts repeatedly and noninvasively are warranted. The goal of the present study was to measure changes in ratios of high energy phosphorus containing metabolites detected with in vivo 31Phosphorous Magnetic Resonance Spectroscopy ((31)P MRS) in a xenotransplantation model and to investigate if these ratios correlated to histological signs of acute xenograft rejection. Thirty-five heart transplantations were performed (NMRI-mice to Lewis (RT1(1)) rats). Thirteen heart transplants underwent repeated daily in vivo (31)P MRS measurements and 22 grafts were measured on any of 4 postoperative days and thereafter sacrificed for histology. A modified scoring system based on Billingham's criteria was used to stage the rejection process. The median graft survival was 3.0 +/- 0.44 (median +/- SD) days (n = 17). Significant differences, both overall and interday, could be calculated for the phosphocreatine (PCr)/beta-adenosine triphosphate (beta-ATP) ratios and for the rejection score. The decreases in PCr/beta-ATP ratios correlated significantly to the progressive acute rejection process in the sacrificed grafts (P = 0.01). Further studies are indicated to establish the potential of (31)P MRS in immunosuppressed recipients of vascularized xenotransplants with prolonged graft survival.
authors.affiliation: Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: D J
authors.initials: DJ
authors.lastname: Lukes
authors.forename: B
authors.initials: B
authors.lastname: Madhu
authors.forename: C
authors.initials: C
authors.lastname: Kjellström
authors.forename: M L
authors.initials: ML
authors.lastname: Gustavsson
authors.forename: L
authors.initials: L
authors.lastname: Mjörnstedt
authors.forename: M
authors.initials: M
authors.lastname: Olausson
authors.forename: B
authors.initials: B
authors.lastname: Soussi
mesh_terms: D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000032:analysis*; D000818:Animals; D004734:Energy Metabolism; D006084:Graft Rejection / Q000175:diagnosis / Q000378:metabolism*; D016027:Heart Transplantation / Q000276:immunology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009200:Myocardial Contraction; D009206:Myocardium / Q000737:chemistry*; D010725:Phosphocreatine / Q000032:analysis*; D010759:Phosphorus Isotopes / Q000032:analysis*; D011184:Postoperative Period; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous / Q000276:immunology*; D016042:Transplantation, Heterotopic
chemical_list: D010759:Phosphorus Isotopes; D010725:Phosphocreatine; D000255:Adenosine Triphosphate