W. johnson high altitude physiology

Cardiovascular Summit3/5/16

How High Altitude Effects Us

2

What is High Alt i tude ?

5000 – 8000 Moderate Altitude 8000 - 12000 High Altitude 12000 – 18000 Very High Altitude 18000+ Extreme Altitude

High A l t i tude Popu lat ions• Most permanent high altitude dwellers show excellent adaption. >140 million people live above 2500 m (8200’).• Adaption to altitude appears to relate to duration and genetics. Ethiopia - oldest and most completely adapted 70000 years 2400 meters 5000 years >2500 meters Amhara (3000-3500 m) Himalayas – 5000 years Andes - 1000-2000 years Rocky Mountains - youngest and least adapted

Population of Summit Co

• 12000 yrs ago Indian Hunter Gatherers

• 4800 B.C. Ute Indians• 1859 (GOLD RUSH) ~10000• WW 1 ~1000• 1970 2665• 1980 8848

(232%)• 1990 12881

(45%)• 2000 23548

(83%)• 2010 29626

(26%)• 2020 *38788

(31%)• 2025 *43943

(13%)

*Summit County growth projections (www.co.summit.co.us/planning/demographics.html

D i ff e r e n c e s I n H y p o x i c Re s p o n s e s

Groves et al. JAP 1993)

High Altitude Cardiology Conditions

HYPOXIA(Sleep Apnea)

Systemic Hypertensio

nPulmonary Hypertension

ArrhythmiasCoagulation?

Coronary Spasm ?

Heart Failure-Diastolic

Dysfunction

Altitude Related Conditions

Acute Mountain Sickness (AMS) High-Altitude Pulmonary Edema (HAPE) High-Altitude Cerebral Edema (HACE) High-Altitude Pulmonary Hypertension(HAPH) High-Altitude Hypertension Arrhythmias may be induced Sleep Apnea Suicide (17.7 vs 5.7 per 100,000 pop.) Skin Cancer Increased longevity (81.3 vs 78 yrs: high vs sea level) Less obesity, heart dis, diabetes and cancer

HIF-1 alpha

Effects of Hypoxia on Pulmonary & Systemic Physiology

Bärtsch P , and Gibbs J S R Circulation 2007;116:2191-2202

PAH: Hemodynamic and Clinical Course

NORMAL

Time

PAP

PVR

CO

INYHA

Adventitia

Media

Intima

Adapted from Gaine S. JAMA. 2000;284:3160-3168.

NORMAL

Adventitia

Media

Intima

REVERSIBLE DISEASE

Time

PAP

PVR

CO

I II III

BNP

NYHA

PAH: Hemodynamic and Clinical Course

Smooth Muscle Hypertrophy

Early Intimal Thickening

Adapted from Gaine S. JAMA. 2000;284:3160-3168.

NORMAL

Adventitia

Media

Intima

Smooth Muscle Hypertrophy

Early Intimal Thickening

REVERSIBLE DISEASE

IRREVERSIBLE DISEASE

Plexiform Lesions

Thrombosis

Adventitial, Intimal Proliferation

Smooth Muscle Hypertrophy

Time

PAP

PVR

CO

I II III IV

BNP

NYHA

PAH: Hemodynamic and Clinical Course

Adapted from Gaine S. JAMA. 2000;284:3160-3168.

Mechanisms of Action of Therapies for PH

Humbert M et al. N Engl J Med. 2004;351:1425-1436.

cGMP

cAMP

Vasoconstriction and proliferation

Endothelinreceptor A

Exogenous nitric oxide

Endothelin-receptor

antagonists

Endothelinreceptor B

Phosphodiesterase type 5 inhibitor

Vasodilatationand antiproliferation

Phosphodiesterase type 5

Vasodilatationand antiproliferation

Prostacyclin derivatives

Nitric Oxide

Endothelin-1

Pre-proendothelin

L-arginine

Prostaglandin I2

L-citrulline

Nitric OxidePathway

EndothelinPathway

ProstacyclinPathway

Endothelial cells

Proendothelin

Endothelial cells

Arachidonic acid

Smooth muscle cells

Prostacyclin (prostaglandin I2)

Smooth muscle cells

RIGHT HEART CATHETERIZATION HEMODYNAMICS

Date 2/14/2012Patient/DOB #5/45 yrsHeight 62"/157 cmWeight 180lbs/82kgBSA 1.83Hgb 16.3

Baseline Rest w/O2 Bike rest Bike Rm Air Bike Rm Air Bike Rm Air Bike O2/res t Bike O2 Bike O2 Bike O2HR 76 60 82 103 139 160 94 104 131 155BP 127/76 119/80 142/93 150/80 166/110 180/110 140/96 170/94 182/94 210/120BP mean 85 93 109 103 129 133 111 119 123 150Watts 0 25 75 100 0 25 75 100Sx/RPE 2 4 7 4 6Minutes 10 3 3 3 3 5 3 3 3FIO2% Rm Air 100% Rm Air Rm Air Rm Air Rm Air 100%NRB 100%NRB 100%NRB 100%NRBArt O2 sat 96 100 92 88 91 87 100 100 100 98RA O2 sat 56RA mmHg 16/10RA mean 13 12 4 11 8 5 3 6 3 3PA O2 sat 61 76 45 35 26 25 46 38 54PA mmhg 51/24 38/19 30/13 67/36 95/50 97/50 39/18 43/20 51/24 61/29PA mean 36 25 21 49 67 67 27 30 35 40PAW mmHg 18/12 21/15 12/5 15/9 26/10 10/4 16/9 20/11 25/5PAW mean 14 19 9 11 17 13 6 12 17 12CO 4.9 4 5.2 14.6 7 8.1 14.6 16.2CI 2.7 2.2 2.8 3.8 3.8 4.4 8.0 8.9PVR Woods 4.5 1.5 2.3 3.7 3.0 2.2 1.2 1.7PVR dynes 359 120 185 296 240 178 99 138SVR Woods 14.7 20.3 20.2 8.8 15.4 14.0 8.2 9.1SVR dynes 1176 1620 1615 701 1234 1116 658 726

Right Heart Cath PAH

Baseline 25w 75w 100w 150w0

20

40

60

80

100

120

mPAP '12mPAW '12O2 Sat '12mPAW '13mPAP '13O2 Sat'13

O2 sat ’12 &’13

mPAW ‘13

mPAP ‘13

mPAW ‘12

mPAP‘12

R i g h t H ea r t C a t h - E xe rc i seRoo m a i r a n d 1 0 0 % O 2

Rest Rm Air Rest 100% O2

Ex Rm Air Ex 100% O20

1020304050607080

mPAP

PVR

4.5

1.5

3.7

1.7

PVR 3 Woods

36

67

40mPAP

25

Maximum Work Load Decreases With Altitude

300' 3300' 5000' 6600' 9900'

-35

-30

-25

-20

-15

-10

-5

0

NormalMild HFSevere HF

Per

cent

cha

nge

Agostoni. Am J Med 2000;109:450-455:

T h a n k s f o r Yo u r At t e n t i o n

Mechanisms of Action of Therapies for PH

Humbert M et al. N Engl J Med. 2004;351:1425-1436.

cGMP

cAMP

Vasoconstriction and proliferation

Endothelinreceptor A

Exogenous nitric oxide

Endothelin-receptor

antagonists

Endothelinreceptor B

Phosphodiesterase type 5 inhibitor

Vasodilatationand antiproliferation

Phosphodiesterase type 5

Vasodilatationand antiproliferation

Prostacyclin derivatives

Nitric Oxide

Endothelin-1

Pre-proendothelin

L-arginine

Prostaglandin I2

L-citrulline

Nitric OxidePathway

EndothelinPathway

ProstacyclinPathway

Endothelial cells

Proendothelin

Endothelial cells

Arachidonic acid

Smooth muscle cells

Prostacyclin (prostaglandin I2)

Smooth muscle cells

PULMONARY HYPERTENSION CLASSIFICATION

I Idiopathic PH/Hereditary PH(BMPR2) 70%+ Drugs & toxins, connective tissue disease, HIV,

cong. heart disease, persistent PH of the new born, and a few others.

II PH assoc with left heart disease.III PH assoc with hypoxemia (lung disease, sleep

apnea, HAPH)IV Thromboembolic PH (acute and chronic) V Unclear multifactorial mechanisms (hematologic,

systemic[sarcoid, histicytosis, vasculitis] thyroid, dialysis, fibrosing mediastinitis, tumors

*JACC Vol. 54, No.1, Suppl S, 2009 6/30/2009,555-66

Pu lmonary Hyper tens ion Preva lence - USA

• IPAH 5.9/million• PE 3-5 %• Scleroderma 21-26%• Heart Failure• Lung Disease• High Altitude ??%

Non-Acclimated Response To High Altitude At Rest

• Increased ventilation• Increased heart rate• Increased cardiac output• Increased blood pressure• Increased pulmonary pressure

Acute Mountain Sickness Symptoms

• Headache• Nausea / Vomiting• Fatigue or Weakness• Dizziness or Lightheadedness• Difficulty Sleeping

Acute Mountain Sickness• Caused by rapid ascent• Symptoms occur around 3000 m (9842 ft)• Develop 4-12 hours after ascent• Resolve in 3-7 days

• People with known disease and/or arrhythmias, increased age, acute altitude exposure, and exercise should use caution and acclimate for several days. Limit stimulants and alcohol, hydrate.

• People with high risks (family history, hypertension, diabetes, abnormal lipids, known disease, elderly) should have a cardiovascular evaluation.

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