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The present study was designed to assess whether acute rejection affects myocardial energy content of the human orthotopically transplanted heart. Adenosine triphosphate content was measured in one tissue sample obtained during 46 routine right ventricular endomyocardial biopsies 6 to 455 days (98 +/- 110) after transplantation in 19 cyclosporine-treated transplant recipients. Tissue samples were immediately frozen in liquid nitrogen within 10 seconds after excision. Adenosine triphosphate analysis was performed with high performance liquid chromatography. Three groups of biopsy specimens were classified according to the standardized cardiac biopsy grading system. Group 1: Eight biopsy specimens without rejection; group 2: 24 biopsy specimens with mild rejection; group 3: 14 biopsy specimens with moderate or severe rejection. Graft systolic function evaluated by echocardiographic fractional shortening was in the normal range the day of biopsy. All patients had normal coronary angiograms within 1 month of the study. In the presence of mild rejection (grade 1A or 1B), adenosine triphosphate content was not significantly different from that of nonrejecting hearts (26.15 +/- 7.1 and 28.57 +/- 8.23 nmol/mg protein, respectively). By contrast, a significant decrease in adenosine triphosphate content was observed when moderate or severe rejection with focal or diffuse aggressive infiltrates were present (10.46 +/- 4.11 nmol/mg protein; p < 0.01 versus two other groups). In seven cases, sequential analysis showed a significant increase in adenosine triphosphate content after rejection therapy concomittant with histologic improvement: 10.19 +/- 2.9 before and 30.13 +/- 7.0 nmol/mg protein after treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)