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

2. 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.

3. 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.

4. Blocked Airflow in Obstructive Sleep Apnea Decreased blood PO 2 (hypoxia)

5. 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.

6. APHR SNS Adrenal Gland or Adipose Tissue

7. 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

8. Metabolic Syndrome

9. The Metabolic Syndrome Visceral Fat Adiponectin Insulin Resistance Diabetes Genetic Environmental Atherosclerosis Hypertension Hyperlipidemia Leptin

10. Obstructive Sleep Apnea Sympathetic Activity Renin-Angiotensin Oxidative Stress Insulin Resistance Hypoxemia Vascular Inflammation Obesity Insulin Resistance Vascular Inflammation Oxidative Stress Endothelial Dysfunction Sympathetic Activity Renin-Angiotensin Obstructive Sleep Apnea Increases the Risk of Cardiovascular Disease Mechanical Obstruction of Airway Risk Factors Dr. John Ciriello, BSc, MSc, PhD Professor of Physiology, Pharmacology and Neuroscience Schulich School of Medicine and Dentistry University of Western Ontario – 2009. Cardiovascular Disease (Risk Factors) Hypertension Stroke Ischemic Heart Disease Cardiac Arrhythmias Atherosclerosis Patients with essential hypertension exhibit augmented increases in sympathetic nerve activity to hypoxia Obese patients exhibit augmented increases in sympathetic nerve activity Ginseng?

11.  3 types Panax quinquefolius Panax ginseng Panax notoginseng  Useful in the treatment of high blood pressure  Useful in the treatment of obesity Ginseng

12.  Protopanaxadiol group (i.e. Rb 1, Rd) show hypotensive effects  Protopanaxatriol group (i.e. Rg 1, Re) show hypertensive effects  Panax ginseng contains approximately equivalent amounts of Rb 1 and Rg 1  Panax quinquefolius often Rb 1 is more abundant Ginsenosides

13.  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 Previous Studies

14.  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

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

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

17.  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. Ginseng and Leptin

18.  Antiobesity Effects of Wild Ginseng (Panax ginseng C.A. Meyer) Mediated by PPAR- γ, 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

19.  Cardiovascular disease is a growing concern in our society Hypertension Obesity Obstructive Sleep Apnea Rationale

20.  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

21.  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 Model

22.  Hypoxia chamber 60s episode at 6-7% O 2 2 min room air (20.5% O 2 ) Total cycle length: 3min 8 hr/day for 21 days  Normoxia chamber Room air Chronic Intermittent Hypoxia

23.  Ginseng extract (Panax quinquefolius) by gavage: 0,125, 250mg/kg in 0.9%saline 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+

24.  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 o Triglycerides o Cholesterol  Peritoneal fat pad  Epididymal fat pad

25. Questions