Histologic pattern of early heart allograft rejection under cyclosporine treatment

The histologic abnormalities associated with early heart rejection in cyclosporine-treated patients are not fully characterized. To study these abnormalities, Lewis rats received ACI heart-lung allografts and two weeks of cyclosporine treatment. Then the therapy was discontinued. Controls were sacrificed at that time; other animals were sacrificed three, six, and nine days later. The rejection score was determined solely by the percentage of necrotic myocardium, while 13 other histologic parameters were semi-quantitatively graded to identify parameters of early rejection of the heart. There was no evidence of myocardial necrosis or significant inflammation three days after discontinuation of therapy. At six and nine days, despite the absence of myocyte necrosis, there were significant increases in the grades for interstitial and endocardial inflammation, venous cuffing, perivascular inflammation with intermyocyte extension and arterial vasculitis. Our quantitative and semi-quantitative histologic analysis identified abnormalities of the early stage of heart rejection that may provide clues in defining rejection prior to the development of myocyte necrosis.