Decreasing ratios of phosphocreatine to beta-ATP correlates to progressiveacute rejection in a concordant mouse heart to rat xenotransplantation model

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 (31)Phosphorous Magnetic Resonance Spect roscopy (P-31 MRS) in a xenotransplantation model and to investigate if the se ratios correlated to histological signs of acute xenograft rejection. Th irty-five heart transplantations were performed (NMR1-mice to Lewis (RT1(1) ) rats). Thirteen heart transplants underwent repeated daily in vivo P-31 M RS 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 phospho creatine (PCr)/beta -adenosine triphosphate (beta -ATP) ratios and for the rejection score. The decreases in PCr/beta -ATP ratios correlated significa ntly to the progressive acute rejection process in the sacrificed grafts (P = 0.01). Further studies are indicated to establish the potential of P-31 MRS in immunosuppressed recipients of vascularized xenotransplants with pro longed graft survival.