Sleep Apnea and Oxidative Stress and Nitric Oxide

We performed a single-center, prospective, randomized, double-blind, placebo-controlled and cross-over clinical study, in which patients received CPAP and sham therapy for two 12-week periods. Baseline measurements in healthy controls matched for age and gender were also obtained. At recruitment, 24-h blood pressure monitoring (ABPM), an echocardiogram (to rule out any cardiac dysfunction) and a sleep study was obtained in all participants . After fasting overnight, a venous blood sample (anti-coagulated with dipotassium EDTA, for 8-isoprostane and total nitrate and nitrite concentration (NOx) determinations) and a urine sample were collected in all of them between 08:00 and 10:00 hours. Within 30 minutes of blood collection, plasma was obtained by centrifugation at 3000 rpm for 15 min. All plasma samples were stored at -60°C until analysis. Patients with OSAS underwent a full-night CPAP titration study using an automated pressure setting device (Auto Set; ResMed, Sydney, Australia). Compliance with therapy was obtained from a built-in run-time counter. After 12 weeks, CPAP device was switched to the alternate mode of therapy and ABPM,, plasma and urine sampling were repeated in patients

Inclusion criteria

• apnea-hypopnea index (AHI) ≥10 h-1
• excessive daytime sleepiness defined by an Epworth scale score ≥11 points
• no treatment for OSAS. Inclusion criteria for healthy control subjects were AHI <5 h-1 and Epworth sleepiness scale <10.

Exclusion criteria

• unwillingness or inability to participate in the study
• obstructive or restrictive lung disease as identified by pulmonary function testing
• use of cardioactive drugs
• cardiac rhythm disturbances, including sinus bradycardia and sinus tachycardia
• known arterial hypertension, or 24-hour mean blood pressure of 135 and/or 85 mm Hg or more
• left ventricular ejection fraction <50%, ischemic or valve heart disease, hypertrophic, restrictive or infiltrative cardiomyopathy, pericardial disease or stroke, by history, physical examination, ECG, chest radiography, conventional exercise stress testing, and echocardiography
• diabetes mellitus, by history or 2 random blood glucose levels ≥126 mg/dl
• morbid obesity (body mass index >40 Kg/m2)
• daytime hypoxemia (PaO2 <70 mm Hg) or hypercapnia (PaCO2 >45 mm Hg)
• need to change medication
• hospital admission for 10 or more days
• average nightly CPAP usage less than 3.5 hours.