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 di agnosis and classification of both moderate and severe acute cellular rejection (International Society for Heart and Lung Transplantation gr ades 3A to 4). However, our previous work suggests that myocyte necros is is not a typical feature of cellular rejection. Methods: To clarify this point and to elucidate differences between cellular rejection an d acute vascular rejection, we compared the light and electron microsc opic features of 35 consecutive endomyocardial biopsy specimens from s ix patients with acute vascular rejection diagnosed with positive immu nofluorescence, 12 consecutive endomyocardial biopsy specimens from th ree patients with mixed acute vascular rejection and cellular rejectio n, and 435 endomyocardial biopsy specimens of International Society fo r Heart and Lung Transplantation grades 2 to 4 cellular rejection. Res ults: 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 my ocardial cell injury. Myocyte necrosis was characterized by lysis of t he sarcolemma, marked swelling of mitochondria, and intramitochondrial flocculent densities. In contrast, the typical form of myocardial cel l injury in cellular rejection was reversible. Reversible cellular rej ection was characterized by extensive loss of myosin filaments and Z-l ines with subsarcolemmal and intracytoplasmic accumulation of Z-band m aterial. Cell swelling, mitochondrial swelling, intramitochondrial den sities, and lysis of sarcolemma were not observed. Conclusions: We con clude that myocyte necrosis is a characteristic feature of acute vascu lar rejection, whereas reversible myocardial cell injury is characteri stic of cellular rejection, including grade 4. Myocyte necrosis is not a feature of cellular rejection. The presence of true myocyte necrosi s in endomyocardial biopsy specimens from cyclosporine-treated heart t ransplants implicates some process other than cellular rejection. Proc esses producing myocyte necrosis include acute vascular rejection, per itransplantation ischemia, and accelerated atherosclerosis.