Cardiovascular Effects of Partial Sleep Deprivation
Condition: Sleep Deprivation
MeSH terms: Sleep Deprivation
Study type: Interventional
Phase: Phase 3

Summary: 
      Background: Sleep curtailment is common and is associated with increased mortality due to
      cardiovascular causes. However, the mechanisms are not completely understood.We hypothesized
      that partial sleep deprivation caused however significant changes in sympathetic activity and
      endothelial function in healthy volunteers.

      Methods: Thirteen young healthy male volunteers will be monitored during 12 days by sleep
      diary and wrist actigraphy. The subjects will keep under their usual daily activities and
      randomized to 5 nights of prolonged sleep (control) or partial sleep deprivation, interposed
      by 2 nights of unrestricted sleep (wash out). At the end of each period, the subjects will be
      evaluate by: 1. electrocardiogram and beat-to-beat blood pressure with spectral analysis of
      heart rate and blood pressure in the supine position and after head up tilt test maneuver; 2.
      resting plasma norepinephrine; 3. venous endothelial function (dorsal hand vein technique).
    

Detailed description: 
      Volunteers Healthy young male volunteers from the urban area of Sao Paulo city will be
      recruited to the study. All subjects will be clinically evaluated, including measurements of
      weight and height. Exclusion criteria include age less than 21 and more than 45 years, body
      mass index (BMI) >25 kg/m2, smoking, use of chronic medications and any established medical
      condition including diabetes mellitus, hypertension, dyslipidemia, heart diseases and sleep
      disordered breathing. After obtaining written informed consent, all participants will be
      submitted to overnight polysomnography.

      Polysomnography Overnight polysomnography will be performed to discarded sleep breathing
      using a digital system (17 channels, EMBLA Medicare - Flaga hf. Medical Devices). All
      polysomnograms will be performed and scored based on the guidelines for sleep studies. The
      apnea-hypopnoea index (AHI) was defined by the number of apneas and hypopnoeas per hour of
      sleep. Sleep disordered breathing was defined by an AHI above 5 events/hour, according to
      standard criteria.

      Sleep Monitoring During the study period all subjects will be continuously monitored by a
      sleep diary and wrist actigraphy (Basic Mini Motionlogger Actigraph Ambulatory Monitoring,
      Inc., Ardsley , New York, USA ) worn on the non-dominant hand. The actigraph will set to
      sample movements in 1 min periods. Actigraph records will automatically process by use of the
      AW2 software version 2.3.01 program (Ambulatory Monitoring, Inc.) to extract information on
      sleep duration.

      Blood Samples Venous blood will be collected from all participants between 8 and 10 AM for
      the measurement of glucose, total cholesterol, low-density lipoprotein, high-density
      lipoprotein, and red blood cell count. Plasma catecholamine (norepinephrine) will be measured
      by High-Performance Liquid Chromatography.

      Hemodynamic and autonomic measurements Hemodynamic and autonomic evaluations will be
      performed in the morning between 8 and 10 AM. The intervals between adjacent QRS complexes
      resulting from sinus node depolarization will be determined (RR intervals). Heart rate will
      be calculated by expressing RR intervals as beats per minute. Non-invasive beat-to-beat blood
      pressure (Finometer, Finapres Medical System BV, Holland) and electrocardiogram (ECG) will be
      continuously recorded by the software AT/MCA-CODAS (DATAC Instruments Inc., Akron, Ohio,
      EUA). The sampling rate was 1000 Hz per channel.

      Autonomic measurements will be derived from spectral analysis of HR and systolic blood
      pressure (SBP). For frequency domain analysis, power spectral density will be obtained by the
      Fast Fourier Transformation using the Welch's method over 16,384 points with a Hanning window
      (512) and 50% overlapping. Spectral power for low- (LF 0.04-0.15 Hz), and high- (HF 0.15-0.4
      Hz) frequency bands will be calculated by means of power spectrum density integration within
      each frequency bandwidth, using a customized routine (MATLAB 6.0, Mathworks). LF/HF ratio
      will be also calculated to evaluate the sympathovagal balance. In addition, we will also
      evaluated the power spectral analysis of SBP.

      The measurements will be evaluated while awake in supine position (5 minutes) and
      subsequently during head up tilt test maneuver (60 degree inclination, 5 minutes). The
      results of tilt test will be expressed as the change between rest and head up tilt .

      Endothelial function Venous endothelial function will be measured by Dorsal Hand Vein
      technique, previously described by Aellig.

      Briefly, a 23-gauge butterfly needle will be inserted into a suitable vein on the back of the
      hand, with the arm positioned at an upward angle of 30 to allow the complete emptying of
      veins. A tripod, holding a linear variable differential transformer (LVDT) (Shaevitz
      Engineering, Pennsuaken, NJ), will be mounted on the back of the hand with the central
      aperture of the LVDT, containing a movable metal core, at a distance of 10 mm downstream from
      the dip of the needle. The signal output of the LVDT, which will be linearly proportional to
      the vertical movement of the core, give a measure of the diameter of the vein. Readings will
      be taken under a congestive pressure of 40 mm Hg by inflating a blood pressure cuff placed on
      the upper portion of the arm under study. Results will be presented as normalized
      dose-response curves in which the diameter of the vein during saline infusion will be defined
      as 100% dilatation. The vein will be preconstricted to 20% of the baseline size by infusing
      increasing doses of phenylephrine, a selective A-adrenergic receptor agonist (25-3166
      ng/min). The infusion rate of phenylephrine inducing 80% venoconstriction will be kept
      constant during the entire study, rate, and this degree of constriction will be defined as 0%
      dilatation for the purpose of subsequent calculations. The vasodilator response expressed in
      this study will be calculated as a percentage of the range between 0 and 100% dilatation.
      Drugs will be infused using a Harvard infusion pump (Harvard Apparatus, South Natick, MA) at
      a flow rate of 0.3 ml/min. After preconstriction of the vein by using phenylephrine, a
      dose-response curve of acetylcholine (0.36-3600 ng/min) and sodium nitroprusside (50-1000
      ng/min) will be constructed with 6 and 2 infusion doses, respectively. Systolic and diastolic
      BP will be determined before and after each experimental phase with a mercury
      sphygmomanometer, and heart rate will be measured by the pulse at the radial artery.

      Experimental Design The entire study period will be of 12 nights. Using a cross over design
      the subjects will keep under their usual daily activities and randomized to 5 nights of
      control sleep or partial sleep deprivation, interposed by 2 nights of wash out (unrestricted
      sleep). During control period, subjects will be instructed to sleep 8 hours, ranging from a
      minimal of 7 hours and a maximum of 9 hours and 30 minutes. Partial sleep deprivation will
      consist of a target sleep between of less than 5 hours, but no less than 3 hours and 30
      minutes. Subjects who will not comply with the sleep schedule will be excluded from the final
      analysis. All measurements described above will be made at the end of control and partial
      sleep deprivation periods.
    

Intervention name(s): Partial sleep deprivation
Intervention type(s): Behavioral
Intervention description(s): Partial sleep deprivation (less than 5 hours, but no less than 3 hours and 30 minutes)
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Keywords: partial sleep deprivation; endothelial dysfunction; sympathetic activity; inflammation