This proposal outlines the first systematic study of the metabolic impact of apnea on a mammalian species that routinely withstands long duration breath-holds while sleeping. The northern elephant seal pup experiences hypoxic conditions during sleep apnea that can not be withstood by terrestrial mammals. As pups and adults, these seals are capable of long duration sleep apnea of up to 30 minutes. The findings will allow basic biological and medical comparisons to humans and other mammals that exhibit abnormal respiratory patterns during sleep. Preliminary studies suggest that sleep apnea in the juvenile seal is a non-steady state condition during which hypoxia tolerance, heart rate changes, blood chemistry variations and substrate utilization patterns are significantly different from patterns seen in sleeping terrestrial mammals and remarkably similar to those seen when seals dive. This study has three major objectives: 1) The basic metabolic characterization of the sleep apnea phenomenon in juvenile seals. 2) The elucidation of similarities between hypoxia tolerance during sleep apnea and metabolic regulation during breath-hold diving. 3) Application of the findings to comparative studies of hypoxia tolerance during sleep apnea or chronic hypoxia in terrestrial species. Studies will include: Measuring shifts in blood gases, heart rate and blood pH during apnea; following the metabolism of plasma borne substrates through aerobic and anaerobic pathways (glucose, fatty acids, lactate); examining the metabolism of hypoxanthine as a clinical marker of hypoxia; following changes in blood flow pattern, hematocrit regulation and peripheral organ perfusion and function; examining tissues for biochemical adaptations to hypoxia. Similar studies on both forced and unrestrained diving seals will provide the data for comparing sleep apnea to the apnea experienced while the seal is awake and diving. Finally, using accepted clinical techniques for modifying central sleep apnea patterns in humans (e.g. oxygen supplementation), efforts will be made to modify and further characterize sleep apnea patterns in seals. This proposal will allow this basic investigation of sleep apnea in the seal to best be used for biological and medical comparative studies.
