Optical and Microdialysis Monitoring of Succinate Prodrug Treatment in a Rotenone-Induced Model of Mitochondrial Dysfunction in Swine

Abstract Succinate prodrug NV354 is a promising therapy for mitochondrial dysfunction. We used diffuse optical and microdialysis techniques to characterize its effects on cerebral oxygen metabolism during rotenone poisoning. One-month-old swine received a four-hour co-infusion of rotenone with either the succinate prodrug NV354 (n = 5) or placebo (n = 5). Cerebral interstitial lactate continually increased in the placebo group (p < 0.01), but lactate levels plateaued in the NV354 group (p = 0.90), which is consistent with NV354’s ability to increase oxygen metabolism in large animals. The study presents first in vivo optical measurements of changes in cytochrome-c-oxidase redox state induced by primary mitochondrial dysfunction and mitochondrial-targeted drugs.