Intragastric ketone ester administration prevents CNS oxygen toxicity (CNS‐OT) and modulates tidal volume and respiratory frequency in rats

Abstract

In clinical and military operations, hyperbaric oxygen (HBO) can generate central nervous system oxygen toxicity (seizures). In a previous study, we demonstrated that the intragastric administration of ketone ester (KE), a non‐ionized ketone bodies precursor, has a prominent anti‐seizure effect. In this follow‐up study, we tested the anticonvulsant properties of multiple KEs, and their effects on cardio‐respiration.60 male rats were implanted with radio‐telemetry devices to record EEG, diaphragmatic electromyogram (dEMG) and ECG. Rats were orally administered with one of four KEs: beta hydroxybutyrate, R,S‐1,3‐butanediol, acetoacetate monoester (AcAc), and acetoacetate diester (AcAc2). 30 min later, rats were exposed to HBO at 5 atmosphere absolute, until the onset of CN‐SOT, and the latency to seizure (LS) was measured.Our results showed that: a) AcAc2 was found to be the most potent anticonvulsant ester, as it increased the LS of 574%, compared to controls; b) AcAc and AcAc2 administration caused a significant increase in tidal volume (VT) and thus minute ventilation c) while stabilizing respiratory frequency (fresp) between 15 min before and after seizure, compared to controls.We report that 1) KEs (notably AcAc and AcAc2) increase the animal's resistance to seizures, and 2) ventilation (VT and fresp) was significantly stimulated by the oral administration of KEs.