Circulation, Vol 84, 1246-1255, Copyright © 1991 by American Heart Association
M Isobe, E Haber and BA Khaw
BACKGROUND. Mice (n = 58) with abdominal heterotopic heart transplants were
studied to examine the effectiveness of 111In-labeled antimyosin
scintigraphy in the detection of rejection and to determine the consequence
of cyclosporine therapy on the results. METHODS AND RESULTS. Allografts
from B10D2 donors were transplanted into B6AF1 recipients. Of the 49
allografted mice, 19 were treated with cyclosporine (15 mg/kg.day). Nine
isografted mice served as controls. Scintigraphy was performed by injecting
100 muCi 111In antimyosin monoclonal antibody 2-15 days after
transplantation. An increase in the ratio of percent dose of antimyosin
injected per gram (% dose/g) of the grafted heart (G) to that of the
autologous heart (A) (G/A) as well as the increasing percent dose per gram
of antimyosin in the grafts reflected the severity of histopathological
rejection regardless of the presence or absence of cyclosporine.
Scintigraphic images demonstrated unequivocally intense accumulation of
111In in rejected allografts as confirmed by histologically demonstrable
myocyte necrosis. The G/A ratio in allografted mice with mildly
deteriorated mechanical activity (4.2 +/- 1.0, mean +/- SD) was greater
than that in mice with normal contractility (1.8 +/- 0.7) (p less than
0.001), and the necrosis correlated with this modest decline in mechanical
function could be scintigraphically identified. Of mice with normally
contracting allografts, the G/A ratio was greater in animals with
demonstrated myocyte necrosis (2.6 +/- 0.5) than in those without necrosis
(1.5 +/- 0.5) (p less than 0.001). In contrast, isografted mice or a subset
of allografted mice treated with cyclosporine and not showing evidence of
rejection did not manifest any significant change in G/A ratio, nor did
they have scintigrams positive for rejection as late as 15 days after
transplantation. CONCLUSIONS. These findings suggest that antimyosin
scintigraphy is a sensitive and early indicator of cardiac transplant
rejection and that it could be useful as a noninvasive method for assessing
the efficacy of cyclosporine treatment.
ARTICLES
Early detection of rejection and assessment of cyclosporine therapy by 111In antimyosin imaging in mouse heart allografts
Cardiac Unit, Massachusetts General Hospital, Boston 02114.
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