Abstract
OBJECTIVES: This study evaluated the effects of sarpogrelate, a selective 5-hydroxytryptamine (5-HT) 2A receptor antagonist, on the preservation of residual hearing and modulation of inflammatory responses following cochlear implantation (CI) in an animal model. METHODS: The damaging effects of CI were simulated in male albino guinea pigs using a dummy electrode. Animals were allocated to three groups: control (n=12, dummy electrode insertion only), SPG-1004 (n=7, low-capacity pump delivering sarpogrelate), and SPG-2004 (n=6, high-capacity pump delivering sarpogrelate). Sarpogrelate was administered via osmotic pumps at two different volumes, and its effects on hearing thresholds, histological outcomes, and expression of inflammation-related genes were assessed. Hearing was evaluated using auditory brainstem response (ABR) thresholds measured at baseline (preoperatively) and at 1, 7, and 30 days postoperatively. RESULTS: Administration of sarpogrelate via an osmotic pump resulted in significant hearing preservation across all tested frequencies at 1 month post-surgery (P<0.05) compared with the control group, which underwent dummy electrode insertion only. Histological analysis revealed that cochlear fibrosis and inflammatory cell infiltration were markedly reduced in the sarpogrelate-treated groups, especially in the group receiving the higher pump volume. Gene expression analysis supported these findings by showing a significant reduction in inflammation-related markers in the sarpogrelate-treated groups. CONCLUSION: Sarpogrelate exhibited a protective effect against the loss of residual hearing after CI, likely due to its anti-inflammatory and antifibrotic properties. In addition, the osmotic pump enabled controlled, sustained delivery of the drug over time. These findings indicate that administering sarpogrelate via an osmotic pump represents a promising pharmacological strategy for improving postoperative outcomes in CI patients by preserving residual hearing.