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

Insomnia

Snoring

Sleep Apnea (Intermittent Hypoxia)

Both Partners Are at Risk of Cardiovascular Disease

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.

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.

Blocked Airflow in Obstructive Sleep Apnea

Decreased blood PO2 (hypoxia)

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.

AP

HR

SNS

Adrenal Gland or Adipose Tissue

Cardiovascular Effects of Chronic OSA

If OSA is left untreated, it can increase the risk of mortality or morbidity as a result of:

AtherosclerosisHypertension Stroke Heart failure Irregular heart beatsHeart attacksWeight Gain

Metabolic Syndrome

The Metabolic Syndrome

Visceral FatAdiponectin

Insulin Resistance

Diabetes

GeneticEnvir

onmenta

l

Atherosclerosis

HypertensionHyperlipidemia

Leptin

Obstructive Sleep ApneaSympathetic ActivityRenin-AngiotensinOxidative Stress

Insulin ResistanceHypoxemia

Vascular Inflammation

ObesityInsulin Resistance

Vascular InflammationOxidative Stress

Endothelial DysfunctionSympathetic ActivityRenin-Angiotensin

Obstructive Sleep Apnea Increases the Risk of Cardiovascular Disease

Mechanical Obstruction of Airway

Risk Factors

Dr. John Ciriello, BSc, MSc, PhDProfessor of Physiology, Pharmacology and NeuroscienceSchulich School of Medicine and DentistryUniversity of Western Ontario – 2009.

Cardiovascular Disease(Risk Factors)Hypertension

StrokeIschemic Heart DiseaseCardiac Arrhythmias

Atherosclerosis

Patients with essential hypertension exhibit augmented increases in sympathetic nerve activity to hypoxia

Obese patients exhibit augmented increases in sympathetic nerve activityGinseng? Ginseng?

Ginseng?

3 types• Panax quinquefolius• Panax ginseng• Panax notoginseng

Useful in the treatment

of high blood pressure

Useful in the treatment of obesity

Ginseng

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

Ginsenosides

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

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

• Anti-hypertensive effect on development of hypertension

SHRSP- alters the development of hypertension starting at 8 weeks of age

• Anti-hypertensive effect in hypertensive SHRSP

at 9-11 weeks of age (maintenance)

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

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

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

Rationale

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

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

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

Chronic Intermittent Hypoxia

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+

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 profileso Triglycerideso Cholesterol

Peritoneal fat pad Epididymal fat pad

Questions