Quantitative spectral analysis of vigilance EEG in patients with obstructive sleep apnoea syndrome: EEG mapping in OSAS patients.

INTRODUCTION: Sleep disruption and blood gas abnormalities, observed in patients with obstructive sleep apnoea (OSA) syndrome, prevent sleep-related restorative processes and induce chemical or structural central nervous system cellular injury. The aim of the study was to determine electroencephalogram (EEG) alterations related to the severity of OSA in patients with OSAS and the effect of the nasal continuous positive air pressure (nCPAP) treatment. MATERIALS AND METHODS: Polysomnography and vigilant EEGs were performed in subjects with possible OSA. The mean relative power was calculated for delta, theta, alpha and beta frequency bands. Thirty subjects without and 131 with OSA participated in this study. In 29 male patients with severe OSA, quantitative EEGs were re-evaluated after 6 months of CPAP treatment. RESULTS: Compared to subjects without OSA, patients with severe OSA showed an increase in relative theta and delta power (occipital, temporal and parietal areas). Six months of nCPAP treatment improved daytime sleepiness of OSA patients. EEG demonstrated a decrease in alpha (frontal, central and temporal areas) and theta (frontal areas) relative power. However, beta relative power was increased mainly in central, and delta relative power, in all brain areas. DISCUSSION: In conclusion, EEG slowing was observed in OSA patients. CPAP treatment improved daytime sleepiness of OSA patients in contrast to the alterations in alpha (decreased) and delta (increased) relative power suggesting a possible persistent brain dysfunction.

Resting tension affects eNOS activity in a calcium-dependent way in airways.

The alteration of resting tension (RT) from 0.5 g to 2.5 g increased significantly airway smooth muscle contractions induced by acetylcholine (ACh) in rabbit trachea. The decrease in extracellular calcium concentration [Ca2+]o from 2 mM to 0.2 mM reduced ACh-induced contractions only at 2.5 g RT with no effect at 0.5 g RT. The nonselective inhibitor of nitric oxide synthase (NOS), N(G)-nitro-L-arginine methyl ester (L-NAME) increased ACh-induced contractions at 2.5 g RT. The inhibitor of inducible NOS, S-methylsothiourea or neuronal NOS, 7-nitroindazole had no effect. At 2.5 g RT, the reduction of [Ca2+]o from 2 mM to 0.2 mM abolished the effect of L-NAME on ACh-induced contractions. The NO precursor L-arginine or the tyrosine kinase inhibitors erbstatin A and genistein had no effect on ACh-induced contractions obtained at 2.5 g RT. Our results suggest that in airways, RT affects ACh-induced contractions by modulating the activity of epithelial NOS in a calcium-dependent, tyrosine-phosphorylation-independent way.

Azithromycin has a direct relaxant effect on precontracted airway smooth muscle.

Macrolides have been proven to have beneficial bacteriostatic and anti-inflammatory properties, but very little is known about the potential value of their bronchodilatory effect. Therefore, in the present study we investigated the effect of azithromycin on contractile responses of isolated rabbit tracheal strips to carbachol or KCl. Azithromycin has a relaxant, concentration-dependent effect on tracheal strips precontracted with carbachol (300 nM), significant from the concentration of 1 muM. The mechanical removal of epithelium did not alter the effect of azithromycin. Azithromycin (100 microM) also relaxed tracheal strips precontracted with KCl (80 mM) even in the presence of atropine (100 microM). Moreover, azithromycin (100 microM) decreased contractions induced by 300 nM and 10 microM carbachol to 55.4% and 80.5% of initial contraction, respectively. The relaxant effect of azithromycin persisted in both calcium free solution and in the presence of the calcium channel antagonist, verapamil. The relaxant effect of azithromycin was not altered by the pre-treatment of preparations with the inhibitors of Ca(2+)-ATPase (cyclopiazonic acid), Na(+)-K(+) ATPase (ouabain), Rho-associated kinase [(R)-(+)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride] (Y-27632) or the non-specific cAMP and cGMP phosphodiesterases inhibitor 3-isobutyl-1-methyl-2,6(1H,3H)-purinedione (IBMX). These results suggest that azithromycin has a concentration-dependent, epithelium-independent, direct relaxant effect on precontracted tracheal strips that is not mediated via inhibition of Ca(2+) influx or Ca(2+) release from intracellular stores. Also, it is not due to alteration of the function of Na(+)-K(+) ATPase and does not depend on the formation of cAMP/cGMP or the Rho/Rho-activated kinase pathway.

Resting tension effect on airway smooth muscle: the involvement of epithelium.

We studied the influence of resting tension (RT) on rabbit tracheal smooth muscle (TSM) contractions induced by acetylcholine or KCl as well as the role of epithelium and the endogenously produced nitric oxide, prostanoids and endothelin on these responses. The alteration of RT from 0.5 to 2.5 g increased the responsiveness of TSM to KCl. The presence of atropine decreased KCl-induced contractions obtained only at 2.5 g RT. The removal of epithelium increased acetylcholine-induced contractions, only at 2.5 g RT. At 0.5 g RT, the presence of L-NAME had no effect on acetylcholine-induced contractions while indomethacin decreased contractions induced by 10(-3) M acetylcholine. At 2.5 g RT, the presence of L-NAME increased acetylcholine-induced contractions while indomethacin, BQ-123 and BQ-788 had no effect. These results demonstrate that RT affects the responsiveness of TSM differentially, depending on the agonist or integrity of the epithelium. Airway epithelium modulates acetylcholine-induced contractions, only at 2.5 g RT partly via NO release. At 0.5 g RT, the endogenous production of prostanoids by sources other than epithelium modulates the contractility of TSM to acetylcholine.

Epithelium-dependent effect of L-glutamate on airways: involvement of prostaglandins.

We investigated the effect of the excitatory amino acid (EAA) receptor agonists L-glutamate, N-methyl-D-aspartate (NMDA), (RS)-a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainic acid on KCl-induced contractions of rabbit tracheal smooth muscle, as well as the role of epithelium and endogenously produced nitric oxide and prostaglandins on these responses. L-Glutamate decreased KCI-induced contractions up to 30%. This effect was attenuated by epithelium removal, tetrodotoxin, methylene blue and indomethacin but not by NG-nitro-L-arginine methyl ester. While NMDA, AMPA and kainic acid had no effect, the combination of NMDA + kainic acid decreased KCI-induced contractions. These results suggest that, in rabbit trachea, L-glutamate has, at least in part, an epithelium-dependent effect mediated via prostaglandin formation and that the EAA receptors involved are non-classical.