HSF Parent Brand

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Sleep Apnea (Intermittent Hypoxia)
Snoring
Insomnia
Both Partners Are at Risk of Cardiovascular
Disease
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Sleep Apnea (Intermittent Hypoxia)

• Apnea is Greek for without breath.
• Sleep Apnea is a serious disorder that occurs
  when a person's breathing is interrupted
  (stopped) during sleep.
• People with untreated sleep apnea stop breathing
  repeatedly during their sleep, sometimes hundreds
  of times.
• Holding your breath leads to decreased blood
  oxygen levels (hypoxia), which has serious
  consequences on the body.

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There Are 2 Types of Sleep Apnea

• Central Sleep Apnea
• The brain fails to signal the muscles to
  breathe, but the airway is not blocked.
• Obstructive Sleep Apnea (OSA)
• The more common of the two forms of apnea.
• It is caused by a blockage of the airway,
  usually when the soft tissue in the back of the
  throat collapses during sleep.
•  

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Blocked Airflow in Obstructive Sleep Apnea
Decreased blood PO2 (hypoxia)
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• What Are The Effects of Chronic OSA?
• Untreated OSA contributes to
• - Recurrent awakenings or insomnia.
• - Sleepiness during the day.
• - Morning headaches.
• - Waking up with a very sore and/or dry throat,
  choking or gasping sensation.
• - Poor performance at work, motor vehicle
  crashes, as well as academic under-achievement in
  children and adolescents.
• - Forgetfulness, mood changes and a decreased
• interest in sex.

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Cardiovascular Effects of Chronic OSA

• If OSA is left untreated, it can increase the
  risk of mortality or morbidity as a result of
• Atherosclerosis
• Hypertension
• Stroke
• Heart failure
• Irregular heart beats
• Heart attacks
• Weight Gain

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Metabolic Syndrome
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The Metabolic Syndrome
Genetic
Environmental
Visceral Fat Adiponectin
Leptin
Insulin Resistance
Hypertension
Hyperlipidemia
Diabetes
Atherosclerosis
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Obstructive Sleep Apnea Increases the Risk of
Cardiovascular Disease
Obstructive Sleep Apnea Sympathetic
Activity Renin-Angiotensin Oxidative
Stress Insulin Resistance Hypoxemia Vascular
Inflammation
Patients with essential hypertension exhibit
augmented increases in sympathetic nerve activity
to hypoxia
Mechanical Obstruction of Airway
Obese patients exhibit augmented increases in
sympathetic nerve activity
Ginseng?
Ginseng?

Obesity Insulin Resistance Vascular
Inflammation Oxidative Stress Endothelial
Dysfunction Sympathetic Activity Renin-Angiotensin

Cardiovascular Disease (Risk Factors) Hypertension
Stroke Ischemic Heart Disease Cardiac
Arrhythmias Atherosclerosis
Risk Factors
Ginseng?
Dr. John Ciriello, BSc, MSc, PhD Professor of
Physiology, Pharmacology and Neuroscience Schulich
School of Medicine and Dentistry University of
Western Ontario 2009.
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Ginseng

• 3 types
• Panax quinquefolius
• Panax ginseng
• Panax notoginseng
• Useful in the treatment
• of high blood pressure
• Useful in the treatment of obesity

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Ginsenosides

• Protopanaxadiol group (i.e. Rb1, Rd) show
  hypotensive effects
• Protopanaxatriol group (i.e. Rg1, Re) show
  hypertensive effects
• Panax ginseng contains approximately equivalent
  amounts of Rb1 and Rg1
• Panax quinquefolius often Rb1 is
• more abundant

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Previous Studies

• Long-term intake of North American ginseng has no
  effect on 24-hour blood pressure and renal
  function (Stavro et al., 2006)
• Panax quinquefolius
• Hypertensive individuals
• 12 weeks
• 3g/day by capsule
• North American Ginseng Exerts a Neutral Effect on
  Blood Pressure in Individuals With Hypertension
  (Stavro et al., 2005)
• 8 mornings- fasted 10-12h, off anti-hypertensive
  medication 12-24h
• 3g/day by capsule. 7 day washout in between
• BP taken for 160mins after treatment

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• Utilization Study of Stems and Leaves of Tienchi
  Ginseng. I. Anti-Hypertensive Effect of Stems and
  Leaves of Tienchi Ginseng on Stroke-Prone
  Spontaneously Hypertensive Rat (SHRSP) (Yanai et
  al.,2006)
• Panax notoginseng- Tea made with extract (4 or
  1)
• No effect of ginseng on SBP in normotensive
  Wistar Kyoto rats
• Measured body weight, urinary volume,
• water intake, food intake, SBP

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• Anti-hypertensive effect on development of
  hypertension
• SHRSP- alters the development of hypertension
  starting at 8 weeks of age

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• Anti-hypertensive effect in hypertensive SHRSP
• at 9-11 weeks of age (maintenance)

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Ginseng and Leptin

• Leptin
• Circulates proportional to adiposity
• Satiety signal
• Increases energy expenditure through sympathetic
  activation
• Leptin deficiency results in obesity
• Leptin resistance in obesity
• Leptin is considered to play an important role
  in the development of hypertension in obesity.

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• Antiobesity Effects of Wild Ginseng (Panax
• ginseng C.A. Meyer) Mediated by PPAR- ?,
• GLUT4 and LPL in ob/ob Mice (Mollah et al., 2008)
• Body weight decreased after 4 weeks of daily
  ginseng treatment in ob/ob rats (100 or 200mg/kg)
• Effect of Crude Saponin of Korean Red Ginseng on
  High-Fat Diet Induced Obesity in the Rat (Kim et
  al., 2004)
• Panax ginseng
• High fat or normal chow for 8 weeks. 3 weeks of
  IP injections of ginsenosides 200mg/kg
• Body weight was reduced by 20-30 in both HF and
  normal diet rats receiving ginsenosides
• Serum leptin levels were lower in high fat diet
  rats after treatment with ginsenosides

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Rationale

• Cardiovascular disease is a growing concern in
  our society
• Hypertension
• Obesity
• Obstructive Sleep Apnea

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• Increase SNS activity by activating peripheral
  chemoreceptors
• OSA patients have high circulating levels of
  leptin
• Hypothesis Ginseng (Panax quinquefolius) will
  reduce circulating levels of leptin thus
  decreasing SNS activation in OSA. Furthermore,
  leptin will have an affect in brainstem areas
  mediating chemoreceptor reflex
• Objective investigate in SHR the effect of
  ginseng on central and peripheral mechanisms
  mediating the effects of leptin on the
  chemoreceptor reflex

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Model

• Sprague Dawley- normotensive rats on a standard
  chow diet
• SHR rats standard chow diet
• SHR rats high-fat, salt diet (45kcal fat, 1.7
  salt)
• SHR rats standard chow diet exposed to
  intermittent hypoxia
• SHR rats high-fat diet exposed to intermittent
  hypoxia

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Chronic Intermittent Hypoxia

• Hypoxia chamber
• 60s episode at 6-7 O2
• 2 min room air (20.5 O2)
• Total cycle length 3min
• 8 hr/day for 21 days
• Normoxia chamber
• Room air

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• Ginseng extract (Panax quinquefolius) by gavage
  0,125, 250mg/kg in 0.9saline every day before 7
  PM for 21 days
• Ethanol and aqueous
• Biweekly measurements of
• Blood pressure and heart rate by Indirect tail
  cuff method (CODA)
• Body weight
• Metabolism Food/water intake, Urinary
• output, Urine Na, K

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• After sacrifice
• Brainstem effects Fos/Fra to detect central
  areas activated in response to administration of
  ginseng
• Circulating levels of leptin
• Plasma NE
• Obesity study
• Lipid profiles
• Triglycerides
• Cholesterol
• Peritoneal fat pad
• Epididymal fat pad

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Questions