Comparison of myocardial cell injury in acute cellular rejection versus acute vascular rejection in cyclosporine-treated heart transplants.

BACKGROUND

Myocyte necrosis has been cited as a key feature in the diagnosis and classification of both moderate and severe acute cellular rejection (International Society for Heart and Lung Transplantation grades 3A to 4). However, our previous work suggests that myocyte necrosis is not a typical feature of cellular rejection.

METHODS

To clarify this point and to elucidate differences between cellular rejection and acute vascular rejection, we compared the light and electron microscopic features of 35 consecutive endomyocardial biopsy specimens from six patients with acute vascular rejection diagnosed with positive immunofluorescence, 12 consecutive endomyocardial biopsy specimens from three patients with mixed acute vascular rejection and cellular rejection, and 435 endomyocardial biopsy specimens of International Society for Heart and Lung Transplantation grades 2 to 4 cellular rejection.

RESULTS

Endomyocardial biopsy specimens from eight of nine patients with acute vascular rejection and mixed acute vascular rejection/cellular rejection exhibited classic myocyte necrosis as the typical form of myocardial cell injury. Myocyte necrosis was characterized by lysis of the sarcolemma, marked swelling of mitochondria, and intramitochondrial flocculent densities. In contrast, the typical form of myocardial cell injury in cellular rejection was reversible. Reversible cellular rejection was characterized by extensive loss of myosin filaments and Z-lines with subsarcolemmal and intracytoplasmic accumulation of Z-band material. Cell swelling, mitochondrial swelling, intramitochondrial densities, and lysis of sarcolemma were not observed.

CONCLUSIONS

We conclude that myocyte necrosis is a characteristic feature of acute vascular rejection, whereas reversible myocardial cell injury is characteristic of cellular rejection, including grade 4. Myocyte necrosis is not a feature of cellular rejection. The presence of true myocyte necrosis in endomyocardial biopsy specimens from cyclosporine-treated heart transplants implicates some process other than cellular rejection. Processes producing myocyte necrosis include acute vascular rejection, peritransplantation ischemia, and accelerated atherosclerosis.