Sleep apnea syndrome affects at least 3% - 5% of the adult population in this country and significant morbidity or even mortality can result from this disorder. It is now well established that the prevalence of sleep-related apnea is dramatically elevated in the elderly with recent estimates ranging from 28% - 67% for elderly males and from 20% - 54% for elderly females. Additional epidemiological data demonstrate strong associations of sleep apnea with hypertension and obesity, and suggest that sleep-related apnea may be an independent risk factor for cardiovascular morbidity and mortality. Despite these facts, the mechanisms of apnea genesis remain poorly understood. This uncertainty stems in part from the lack of an appropriate animal model by which apneas may be studied in all stages of sleep. We have recently extended the work of others to characterize a rat model of physiological apnea, demonstrating that rats of various strains, including obese, hypertensive, pigmented and albino rats, express spontaneous apnea at rates of 3 - 10 and 10 - 30 per hour of nonrapid eye movement and rapid eye movement sleep, respectively. We have collected preliminary data which indicate that: 1) apnea expression increases robust1y as individual rats age from 3 months to 12 months and 2) in comparison to 3 month old rats, apnea indexes are higher in groups of 17 and 26 months old rats; thus suggesting that the rat may serve as a valuable animal model of the age-related increase in sleep apnea. In this pilot study we will measure sleep-related respiratory and cardiovascular behaviors longitudinally in multiple age-cohorts of Sprague-Dawley rats, the strain for which apnea expression has been best characterized in young adults. These protocols will clearly determine any age-related changes in apnea expression as well as the sleep state dependencies of this effecL Correlated changes in chemoreflexes and baroreflexes during sleep will also be identified. At the conclusion of this one year program, the feasibility of using the rat as an animal model of sleep apnea in aging should be clearly demonstrated. If positive, these findings will constitute the core of preliminary work necessary for a competitive R01 application to either the NIA or the NHBLI focused on identifying the mechanisms underlying age-related changes in apnea expression in the rat.
| Carley, D W; Berecek, K; Videnovic, A et al. (2000) Sleep-disordered respiration in phenotypically normotensive, genetically hypertensive rats. Am J Respir Crit Care Med 162:1474-9 |
| Carley, D W; Radulovacki, M (1999) Role of peripheral adenosine A(1) receptors in the regulation of sleep apneas in rats. Exp Neurol 159:545-50 |
| Carley, D W; Radulovacki, M (1999) Role of peripheral serotonin in the regulation of central sleep apneas in rats. Chest 115:1397-401 |
| Carley, D W; Radulovacki, M (1999) Mirtazapine, a mixed-profile serotonin agonist/antagonist, suppresses sleep apnea in the rat. Am J Respir Crit Care Med 160:1824-9 |
| Carley, D W; Trbovic, S M; Radulovacki, M (1998) Diazepam suppresses sleep apneas in rats. Am J Respir Crit Care Med 157:917-20 |
