No abstract

In the adult rat, exposure to intermittent hypoxia (IH), such as occurs in sleep-disordered breathing, is associated with neurobehavioral impairments and increased apoptosis in the hippocampal CA1 region and cortex. We hypothesized that the episodic hypoxic-reoxygenation cycles of IH would induce oxidant stress, and the latter may underlie the IH-associated spatial learning and retention deficits. Adult male rats were therefore exposed to IH (90-second alternations of 10% oxygen and 21% oxygen) or room air (RA) for 7 days, and received twice-daily injections of either 3 mg/kg of the antioxidant PNU-101033E (PNU) or vehicle (V). Rats were then trained in a standard place-training task in the water maze. V-IH displayed significant impairments of spatial learning in the water maze, which were attenuated by PNU-101033E. Post hoc analyses further revealed that V-IH had significantly longer latencies and pathlengths to locate the hidden platform than PNU-IH, V-RA, or PNU-RA, indicating that PNU-101033E treatment reduced the behavioral impairments associated with IH. In addition, treatment with PNU-101033E markedly attenuated the increase in lipid peroxidation, and isoprostane concentrations associated with exposure to IH. Collectively, these findings indicate that the IH exposure is associated with increased oxidative stress, which is likely to play an important role in the behavioral impairments observed in a rodent model of sleep-disordered breathing.

Financial Disclosure: Drs Kheirandish and Gozal are the recipients of an investigator-initiated grant from Astra Zeneca Ltd for an unrelated research project on the effect of intranasal budesonide in mild sleepdisordered breathing in children. Dr Gozal serves on the national speaker bureau of Merck. ABSTRACTOBJECTIVE. Tonsillectomy and adenoidectomy (T&A) is the primary therapeutic approach for sleep-disordered breathing (SDB) in children. However, residual mild SDB will be found in more than one third of these patients after T&A. We hypothesized that combined therapy with the leukotriene receptor antagonist montelukast and intranasal budesonide would result in normalization of residual SDB after T&A.METHODS. During the period of October 2002 to February 2005, children who underwent T&A for SDB underwent a routine postoperative (second) overnight polysomnographic evaluation (PSG) 10 to 14 weeks after T&A surgery. In children with residual apnea hypopnea index (AHI) Ͼ1 and Ͻ5/hour of total sleep time (TST), treatment with montelukast and intranasal budesonide aqueous solution was administered for a period of 12 weeks (M/B group), at which time a third PSG was performed. Children who had residual SDB and did not receive M/B therapy from their treating physicians were recruited as control subjects.RESULTS. Twenty-two children received M/B, and 14 children served as control subjects. Mean age, gender distribution, ethnicity, and BMI were similar in the 2 treatment groups. The mean AHI at the second PSG was 3.9 Ϯ 1.2/hour of TST and 3.6 Ϯ 1.4/hour of TST in M/B-treated and control patients, respectively. Similar nadir arterial oxygen saturation (87.3 Ϯ 1.2%) and respiratory arousal index (4.6 Ϯ 0.7/hour of TST) were recorded for both groups. However, the M/B group demonstrated significant improvements in AHI (0.3 Ϯ 0.3/hour of TST), in nadir arterial oxygen saturation (92.5 Ϯ 3.0%), and in respiratory arousal index (0.8 Ϯ 0.7/hour of TST) on the third PSG, whereas no significant changes occurred over time in control subjects.CONCLUSIONS. Combined anti-inflammatory therapy that consists of oral montelukast and intranasal budesonide effectively improves and/or normalizes respiratory and sleep disturbances in children with residual SDB after T&A. O BSTRUCTIVE SLEEP APNEA and sleep-disordered breathing (SDB) is a common and highly prevalent disorder in the pediatric age range that affects 2% to 3% of all children. 1 When left untreated, SDB is associated with substantial morbidity, primarily affecting neurobehavioral and cardiovascular systems. 2-9 Thus, because in otherwise normal children SDB is attributed primarily to adenotonsillar hypertrophy, 10,11 tonsillectomy and adenoidectomy (T&A) is currently the most common treatment for children with SDB. 12 However, although a recent meta-analysis of the published literature suggested a relatively high success rate for T&A, averaging ϳ85%, 13 the overall short-term cure rates for this surgical procedure in otherwise healthy children may not be as favorable as previously an...