Kinetics and dynamics of acute rejection after heterotopic heart transplantation

Right cervical, heterotopic heart transplantation was performed in 18 mongrel dogs. Study design was based on three different groups (n = 3 x 6). Standard immunosuppression consisted of triple drug therapy in all dogs. Groups II and III received high dose steroids during acute rejection. In group III the native hearts of previous recipients (groups I and II) were used as donors for heterotopic transplantation ("domino" principle). The hearts were examined by daily transmural biventricular biopsies and graded according to Billingham classification. Cytoimmunologic monitoring (n = 345; activation index from peripheral and coronary sinus blood) and fast Fourier transformation ECG (n = 80; area under the curve; surface recordings) served as daily noninvasive methods. Optionally antimyosin scintigraphy (n = 25; single photon emission computed tomography; heart-to-lung ratio) was performed and immunohistologically confirmed by peroxidase staining of the antibody (n = 61). Kinetics of rejection was not uniform in group I (onset after 5.7 days) and biphasic in group II (clear rejection-free interval: 6.8 days). Group III developed a continuously persisting rejection, despite repeated high-dose steroids, with an early onset (3.2 days). The invasive data, consisting of 587 punch biopsies, showed no significant difference between right and left ventricular rejection. Clearly focal rejection appeared in 51.5% of the cases, with subendocardial involvement in 54%. Cytoimmunologic monitoring significantly (p less than 0.001) correlated with daily biopsies in groups I and II. The activation index from coronary sinus blood was two times higher than in peripheral blood. Fast Fourier transform ECG identified the onset of rejection with great accuracy (p less than 0.01). The heart-to-lung ratio of antimyosin scintigraphy corresponded exactly to the various stages of rejection (p less than 0.001). High-dose steroids led to a clear reduction of the ratio in 26% cases. Peroxidase staining showed typical locations of the antibody, depending on the grade of rejection (p less than 0.001). Considering the results of pathology in this transplantation model, relying on endomyocardial biopsy alone in a clinical setting may not seem advisable. Although the results of this study must be confirmed clinically, the simultaneous use of cytoimmunologic monitoring and fast Fourier transformation ECG may prove to be valuable to day-to-day monitoring for acute rejection in the early postoperative course. If both methods indicate the onset of an acute rejection, antimyosin scintigraphy and endomyocardial biopsy, respectively, should be performed to confirm and grade the suspected diagnosis.