Coronary blood flow and thallium 201 uptake in rejecting rat heart transplantations

The effects of rejection on coronary flow (CAF) in heart allografts are unclear, although previous evidence with cardiac imaging agents indicates impaired flow during advanced rejection. The purpose of this study was to measure CAF in heterotopically placed heart grafts. Lewis rats (LEW) received grafts from either syngeneic Lewis rats (LEW/LEW group) or allogeneic ACI rats (ACI/LEW group). CAF was measured in both the transplanted and native hearts with radiolabeled microspheres. Rejection was measured histologically (grades 0 [absent] to 4+ [severe]). In addition systemic blood pressure and cardiac outputs of the native hearts were determined with microspheres. Different animals were studied during relatively early (4 days) and late (6 day) rejection. Among the 4-day animals a cyclosporine-treated group was included (ACI/LEW CyA). In 6-day rats CAF in allografts was lower (0.56 ± .06 ml/gm/min) compared with syngeneic grafts (1.72 ± 0.4 ml/gm/min) (p < 0.05). The CAF in the native hearts did not differ significantly but was higher than in the grafts in both groups. Heart rates were reduced in allografts (p < 0.05). It is interesting that arterial pressure and cardiac output were significantly lower in animals bearing allogeneic than syngeneic grafts. In rats studied at 4 days graft CAF was lower than in the native heart in both the LEW/LEW and ACI/LEW groups, but there was no significant difference in behavior between groups. The same was true for a cyclosporine-treated group. Graft heart rates were similar in all 4-day rats. These data suggest that the reduction in CAF seen in allografts in late rejection may be the result of reduced heart rate but does not exclude that a primary reduction in graft flow contributes to allograft destruction. The reduced systemic blood pressure and cardiac output in animals bearing allografts in severe rejection indicates the release of a cardiodepressant during rejection, because the graft does not contribute to systemic circulation in this model.