Effects of 5-Hydroxymethyl-2-Furfural (5-HMF) on Skeletal Muscle Performance in Rats Exposed to an Acute Bout of Hypobaric Hypoxia
Exposure to high altitude is associated with a reduction in the partial pressure of oxygen (PO2) that subsequently affects all components of the oxygen transport cascade, from lung to mitochondria. Impaired oxygen transport contributes to decrements in exercise capacity at high altitude. Strategies aimed at improving blood oxygenation are therefore an important focus of study. 5-hydroxymethyl-2-furfural (5-HMF) may offer prophylaxis at high altitude due to induction of a leftward-shift in the oxygen-hemoglobin dissociation curve that results in increased arterial blood oxygen saturation. The objective of this research is to determine whether the benefits afforded by 5-HMF to blood oxygenation create a measureable attenuation in the decline in physical performance known to occur in hypoxia. Fisher 344male rats (n=40) were implanted with osmotic pumps to continuously deliver either inactive saline or 5-HMF (40 mg/kg/d), and exposed to either sea level(SL, n=20/group) or a simulated altitude of 18,000 feet (HH, n=20/group) in ahypobaric hypoxic chamber for 24 hours. Muscle function testing was conducted both pre- and post-HH and SL exposures, including peak torque output, force-frequency analysis, and time to fatigue. Following SL/HH exposure, animals had repeat muscle function testing, then were weighed, had blood collected for determination of blood gases and complete blood counts (CBC), and were humanely euthanized. Muscles were then harvested with wet weights recorded. Rats exposed to HH for 24 hours displayed a 9% decrease in body mass. In 5-HMF treated animals, increases in erythrocytes (14%), hemoglobin (14%) and hematocrit (16%) were documented. HH led to a 38% reduction in PO2; however 5-HMF did not attenuate this decline. Posterior crural muscle strength was unaltered in HH-exposed rats, and although non-significant, a 9% increase in peak torque output was documented in 5-HMF treated animals. In spite of 5-HMFimproving blood oxygen carrying capacity, only modest improvements were observed in muscle function following a 24 hour exposure to a simulated altitude of 18,000 ft. Current studies are underway to assess the benefits of5-HMF on blood oxygenation with extended HH exposure. In addition, these experiments will determine whether overt alterations in anabolic pathways occur and precede outward functional changes in muscle.
