Use of cyclosporine in the mouse heterotopic heart transplant model

We refined the mouse ear-heart transplant model developed by Fulmer and coworkers and tested cyclosporine as a sole immunosuppressive agent in this model. Three-week-old CBA mice were used as heart recipients, and unsexed newborn BALB/c mice were used as heart donors. The heart grafts were examined for visible pulsations at 10-fold to 20-fold magnification daily for the first 10 days and every other day thereafter. Graft electrocardiograms were also obtained on the same schedule. Preliminary studies had established that a dose of 15 mg/kg/day was the optimal cyclosporine dose in our model. This dose was administered subcutaneously to each of two treatment groups. Group 2 received this dose for the entire 30-day experimental period. Group 3 received this dose for the first 16 days of the experimental period. Group 1 consisted of allografts receiving no immunosuppression. Group 1 grafts showed evidence of initial successful engraftment by day 7; however, by day 13 none of the grafts remained viable. In group 2, 19 of 23 grafts remained viable for the entire experimental period. In group 3, all of the grafts remained viable until day 17 (after day 16 cyclosporine was discontinued) and rapidly lost evidence of viability thereafter. By day 21, none of the grafts in group 3 remained viable. Survival curves for the three groups as determined by electrocardiogram and visible pulsations were constructed, and the differences between the curves were significant (p = 0.001). The results of this study demonstrate the potential usefulness of the ear-heart transplantation model in screening immunosuppressive agents.(ABSTRACT TRUNCATED AT 250 WORDS)