IC87201, a PSD-95/nNOS Inhibitor, Ameliorates Heart Rate Variability in the Rat Model of Middle Cerebral Artery Occlusion

Abstract

Objective: Assessment of heart rate variability (HRV) is a non-invasive and reliable method to evaluate autonomic disorders after cerebral ischemia. The present study was conducted to investigate the therapeutic potential of IC87201 in reducing post-stroke cardiac dysfunction. Materials and methods: Cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) method in 15 anesthetized adult male rats in three MCAO, MCAO+ DXM, and MCAO+ IC87201 groups, for one hour. Electrocardiogram was recorded before, and 48 hours after ischemia and drug administration, and HRV parameters were calculated from R-R intervals. In the treatment groups, IC87201 and Dextromethorphan hydrobromide monohydrate (DXM) were injected after an ischemic period. Results: After brain ischemia, the R-R interval decreased and consequently heart rate increased. The R-R intervals were used to extract the HRV frequency and time domains, including normalized low frequency (LF), high frequency (HF), LF/HF ratio, and standard deviation of R-R interval (SDRR). Normalized LF and LF/HF ratio enhanced 48 hours after ischemia, while normalized HF and SDRR significantly reduced compared to the pre-ischemic state. All HRV parameters had returned to their pre-ischemic level 48 hours after IC87201 and DXM administration, except SDRR, which recovered only in the IC87201 administered group. Conclusion: Based on our findings, it can be concluded that cerebral ischemia significantly worsens HRV parameters as a result of sympathetic overactivity. These changes were reversed by administering DXM and IC87201, but IC87201 has generally been more effective in lowering lesions. As a result, IC87201 can be introduced as an effective substance for the treatment of post-ischemic cardiac side effects.