Metabolic changes preceding functional and morphologic indices of rejection in heterotopic cardiac allografts. A 31P nuclear magnetic resonance study.

Eight beagles receiving heterotopic (cervical) cardiac allografts from outbred donors were evaluated by serial 31P NMR, septal endocardial biopsy, and left ventricular pressure measurements for signs of rejection. Early postoperative myocardial energy levels, as assessed by ratios of phosphocreatine to inorganic phosphate (PCr/Pi) and phosphocreatine to beta-ATP (PCr/B-ATP), were acceptable in all recipients. In these nonimmunosuppressed animals, the mean ratios of PCr/Pi and PCr/B-ATP progressively decreased, with a greater than 25% reduction noted by postoperative day two and greater than 50% reduction by day three. In sharp contrast, left ventricular end-diastolic pressures remained stable and at baseline levels for the first three postoperative days, and only then markedly increased. Likewise, histologic evidence of rejection did not become prominent until postoperative day four. These results suggest that metabolic abnormalities significantly precede either functional or histologic changes in rejecting allografts. The early detection of these metabolic changes by 31P NMR appears to have important potential for the noninvasive diagnosis of cardiac allograft rejection.