Cyclosporine Dose, Serum Trough Levels, and Allograft Preservation in a Rat Model of Laryngeal Transplantation

Using a rat model of laryngeal transplantation, we sought to define the relationships between acute laryngeal rejection grade (RG) and cyclosporin A (CSA) concentration and CSA dosage. Five recipient Lewis rat groups (N = 10 per group) were administered intramuscular CSA doses of 1.0 (group 1), 2.5 (group 2), 5.0 (group 3), 7.5 (group 4), and 10 mg/kg per day (group 5) for 14 days. Immediately before sacrifice, 5 mL of whole blood was obtained to assay CSA trough levels by high-performance liquid chromatography. The specimens were graded microscopically by blinded reviewers by day of RG, 0 to 14 days after transplantation, as described in earlier reports. Despite high intragroup variability in CSA levels, significantly different mean CSA concentrations were achieved among all CSA dosage groups: 1,2,3,4, and 5 (.0001 < p < .02). The mean laryngeal RGs did not test significantly different from each other with groups 3, 4, and 5 (RG, 2.3 ± 1.3 versus 1.9 ± 1.1 versus 1.7 ±0.3, respectively, .2 < p < .6). The RG for group 1 was significantly greater than those for groups 2 through 5 (p < .001), and the group 2 RG was greater (p < .02) than those for groups 3, 4, and 5. Polynomial fitting was used to determine the continuous relationship between each individual specimen's CSA concentration and the RG. Significant pathological allograft rejection correlated with CSA concentrations below 250 ng/mL.