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