US Army Research Institute of Environmental Medicine Medicine and Work Performance at High Altitude...

US Army Research Institute of Environmental Medicine

Medicine and Work Performance atHigh Altitude

Stephen R. Muza, Ph.D.U.S. Army Research Institute of Environmental Medicine

Natick, MA, USA 01760

The opinions or assertions contained herein are the private views of the author(s) and are not to be construedas official or as reflecting the views of the Army or the Department of Defense.


Overview

1. Biophysics of the Altitude Environment

2. Altitude Acclimatization:

Key Physiological Adaptations

Time-Course

3. High Altitude Stress:

Medical Problems - Altitude Illness

Performance – Physical & Neuropsychological


Easy Access to High Altitude Createsa Health and Performance Problem

Colorado Collegiate Range

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Biophysics of High Altitude

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Mt. Mckinley, AK

Mt. Everest, Nepal

Boston, MA

Salt Lake City, UT

Human Performance Physiology and Environmental Medicine at Terrestrial Extremes, 1988Medical Aspects of Harsh Environments, 2002


PaO2 (mmHg)

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4300 m (Pikes Peak, CO)

Biophysics of High Altitude

SL: CaO2 = 19.6 ml O2%1850 m: CaO2 = 19.2 ml O2%4300 m: CaO2 = 16.5 ml O2%


High Altitude Stress:Impact on Low Altitude Residents

• Decreased Physical Performance (>1,200 m)• Risk of Altitude Sickness (>2,400 m)• Decreased Neuropsychological Performances (>2,400 m)

Medical Aspects of Harsh Environments , 2002


High Altitude Stress:Acute Physiological Responses

• Increased alveolar ventilation• Increased heart rate, and cardiac output• Peripheral vasodilation• Pulmonary arterial vasoconstriction• Increased 2,3-diphosphoglycerate • Increased epinephrine release from adrenal medulla• Increased HIF-1 up regulates >100 genes: EPO, VEGF, HSP(s)• ???

PIO2 PAO2 PaO2 Disruption in Homeostasis


High Altitude Stress:Acute Physiological Responses: HIF Target Genes

Bernhardt, W.M. et al 2007


High Altitude Stress:<1% of All Genes Changed Over Acclimatization


High Altitude Stress:Acute Physiological Responses


e.g.: Increased Alveolar Ventilation Causes Respiratory Alkalosis


High Altitude Stress:Summary of Acute Physiological State

• Systemic hypoxia• Respiratory alkalosis (disrupted acid-base balance)• Orthostatic intolerant (light-headed, syncope)• Pulmonary arterial hypertension (impaired gas exchange)• Altered body fluid regulation: vascular space is leaking, some

tissues develop edema• ???



Altitude AcclimatizationA series of physiological adjustments that

compensate for the reduction in ambient oxygen, and restores homeostasis

Table 2–4Summary of major physiological adaptations characteristic of altitude acclimatizationTable 2–4Summary of major physiological adaptations characteristic of altitude acclimatization

• Restored Mental Performance: 1-2 Days

• Decreased Susceptibility to Altitude Illness: 2-5 Days • Improved Sleep Quality: 5-7 Days

• Improved Physical Work Performance: 5-14 Days

• Overall, improved Resilience

Benefits of Acclimatization:


Altitude Acclimatization

Increase Oxygen Delivery Increase Oxygen UtilizationIncreased Ventilation: Raises partial pressure of arterial O2 (PO2) and arterial oxyhemoglobin saturation (SaO2)

Increased Tissue Extraction of O2 from Capillary Blood

Decreased Plasma Volume: Raises arterial O2 content via increased hemoglobin concentration [Hb]

Increased Carbohydrate Transport and Utilization

Increased 2,3-diphosphoglycerate and Renal Bicarbonate Excretion: Promotes O2 unloading from hemoglobin

Hypoxia-Inducible Factor (HIF)-Mediated Increased Oxidative Enzyme Function

Increased Sympathetic Activity: Sustains blood flow and blood pressure

Erythropoietin Mediated Increase in Red Blood Cell Mass: Raises arterial O2 content


Summary of major physiological adaptations characteristic of altitude acclimatization


Time Course of Altitude Acclimatization




Increase Oxygen Delivery Increase Oxygen UtilizationIncreased Ventilation: Raises partial pressure of arterial O2 (PO2) and arterial oxyhemoglobin saturation (SaO2)

Increased Tissue Extraction of O2 from Capillary Blood

Decreased Plasma Volume: Raises arterial O2 content via increased hemoglobin concentration [Hb]

Increased Carbohydrate Transport and Utilization

Increased 2,3-diphosphoglycerate and Renal Bicarbonate Excretion: Promotes O2 unloading from hemoglobin

Hypoxia-Inducible Factor (HIF)-Mediated Increased Oxidative Enzyme Function

Increased Sympathetic Activity: Sustains blood flow and blood pressure

Erythropoietin Mediated Increase in Red Blood Cell Mass: Raises arterial O2 content


Summary of major physiological adaptations characteristic of altitude acclimatization


Altitude AcclimatizationVentilatory Acclimatization: Increased Hypoxic Ventilatory Response (HVR) Decreased PaCO2 set point Near normalization of pHa Compensated Respiratory Alkalosis Elevated PaO2, SaO2, and CaO2

Altitude Exposure (days)

SL 1 2 3 4 5 7 10

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4422 Women37 Men

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22 Women (Muza et al. 2001)37 Men (Reeves et al. 1993)


Altitude AcclimatizationHematological Acclimatization: Early Response:

Decreased Plasma Volume Increases [HB] Long-term Response (up to 18 months):

Stimulation of Erythropoietin Increases RBC mass Near normalization of CaO2


SL 1 2 3 6 9 11 13 21

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Lyons et al. 1995Sawka et al. 1996Wolfel et al. 1991


SL 1 2 3 6 9 11 13 21

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Lyons et al. 1995Sawka et al. 1996Wolfel et al. 1991Reeves et al. 2001



Ward, Milledge & West, 2000

Long-term Adaptation:

Tibetans:High HVR,Low PHPRLarger TLC


ABOVE 8,000 ft (2,400 m):

Slow ascent (no greater than 1,000 ft/day)

Staged ascent (4 - 10 days at 6,000 - 8,500 ft)

Intermittent Altitude Exposures (4+ hr exposure

to high altitude each day for 1 or more weeks)

• Ascend High Enough to Induce Acclimatization, but Not Too High

• Reside at High Altitude for a Sufficient Length of Time

• Methods For Inducing Acclimatization:Staged or Gradual Ascent ProfilesIntermittent Altitude Exposure Protocols

Altitude AcclimatizationProcedures


Staged Ascent Acclimatization Strategies

Ascend high enough to induce acclimatization, but to avoid developing AMS, do not ascend too high or too fast.

After staging, single day ascent up to 2,000 m above staging altitude has low risk of AMS.


Graded Ascent Acclimatization Strategies

Ascend high enough to induce acclimatization, but to avoid developing AMS, do not ascend too high or too fast.

Recommendations: above 2,400 m no more than 300 m/d.Add a rest day every 900-1,200 m.


High Altitude Stress:Acute Physiological State

• Medical Issues:

Altitude Sickness and Deterioration

• Performance Issues:

Physical and Neuropsychological



Acute Mountain Sickness

High Altitude Cerebral Edema

High Altitude Pulmonary Edema

High Altitude Retinal Hemorrhage

High Altitude Peripheral Edema

High Altitude Bronchitis

Chronic Mountain Sickness

Altitude Sickness


Susceptibiity:

Currently not predictable, but maybe?

Individual susceptibility is reproducible

Men greater susceptibility than women

Risk Factors:

Unacclimatized state

Rapid ascent >2400 m

Exercise or heavy physical work

Hypohydration

Very, very low HVR

Cold Exposure

Obesity

Compromised cardiopulmonary function

Age < 50 yrs

Altitude Sickness


Altitude Sickness

Acute Mountain Sickness (AMS) – “most common” Incidence: 20 – 90% Symptom Complex: Headache, Nausea, Vomiting, Lassitude,

Dizziness, Insomnia

High Altitude Cerebral Edema (HACE) – “rare below the death zone” Incidence: ~1% Symptom Complex: Severe Headache, Impaired Mental Status,

Truncal Ataxia, Coma

High Altitude Pulmonary Edema (HAPE) – “leading cause of death” Incidence: 5-15% Symptom Complex: Dyspnea, Severe Fatigue,

Non-productive Cough, becoming productive,Pink & Frothy, Coma

Roach , R.C. et al., Medical Aspects of Harsh Environments , 2002


Beidleman, B.A.. et al., Med. Sci. Sports Exerc.:45, 2013

Acute Mountain Sickness (AMS)

Prediction of AMS:•Time and altitude are key factors•AMS increases 145% every 1000 m•AMS severity peaks 18-24 h•Physical activity increases AMS•Physical activity delays recovery from AMS•Women have lower AMS severity


AMS Criterion

Days at 4,300 m Altitude

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Acute Mountain Sickness (AMS)Time Course


Acute Mountain Sickness (AMS)Pathophysiology

Prevailing theory: hypoxia-induced mild edema of both cytotoxic (intracellular) and vasogenic (extracellular) origin

Evidence: DW-MRI, volumetric MRI, CSF volume, IR-NIR scattering

Problem: everyone affected, no correlation with AMS symptoms, no evidence of BBB failure

Recent controversial theory: hypoxia-induced cerebral oxidative-nitrative stress releases noxious biomolecules that activate trigeminovascular nocioceptors to cause headache and AMS (Bailey, D.M. et al, 2009)


High Altitude Cerebral Edema (HACE)Pathophysiology

Prevailing theory: continuum of AMS progressing to vasogenic edema

33 yr male, SL to 5200 m in 6 days,MRI day 2 and 11 months later

MRI of acute and recovered phases of HACE. 7 of 9 patients with HACE showed intense T2 signal in white matter areas, especially the splenium of the corpus callosum.(Hackett, P. et al., JAMA 1998)


Altitude Hypoxia

PaO2

Uneven HPVR

Pulmonary Htn

Pulmonary Pcap

Capillary Stress Failure

Pulmonary Capillary Leak

High Altitude Pulmonary Edema

SNS

Pulmonary Venoconstriction

Vascular PermeabilityAgents?

(exercise, cold)(Endothelin-1, NO)

(HVR, A-a O2, exercise, sleep)

( Alveolar Fluid Absorption)

High Altitude Pulmonary Edema (HAPE)Pathophysiology

HAPE Status

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Altitude acclimatization above 1,200 m

For AMS consider Diamox (Acetazolamide)

- carbonic anhydrase Inhibitor facilitates HCO-3 diuresis

For HACE consider Dexamethasone (corticosteroid)

For HAPE consider Nifedipine (calcium channel blocker),

Sildenafil, Tadalafil (5-PDE Inhibitor),

Salmeterol (2-adrenergic agonist)

Altitude SicknessPrevention


Stop ascentDescend (most efficacious treatment)RestMedications listed for preventionOxygenHyperbaric treatment bag (>2 psi)

Altitude SicknessTreatment


HIGH ALTITUDE DETERIORATION

Key Features:

>5000 m long-duration exposuresExcessive weight lossPoor appetiteSlow recovery from fatiguePoor wound healingLethargyIrritabilityLack of willpowerPossible permanent brain damage


High Altitude Stress:Acute Physiological State

• Medical Issues:

Altitude Sickness and Deterioration

• Performance Issues:

Physical and Neuropsychological



Altitude Impact on Physical Work Performance

Maximal Aerobic Exercise Performance

Fulco CS, et al., Aviat Space Environ Med 69: 793-801, 1998

146 mean data pointsfrom 67 studies


PaO2 (mmHg)

0 20 40 60 80 100 120 140

Oxy

gen

Sat

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tio

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%)

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Sea Level

1850 m (Colorado Spgs, CO)

4300 m (Pikes Peak, CO)

Decreased Maximal Arterial Oxygen Delivery

SL: CaO2 = 19.6 ml O2%1850 m: CaO2 = 19.2 ml O2%4300 m: CaO2 = 16.5 ml O2%


At Sea Level (SaO2=97%):

4200 ml/min = 25 L/min x (196-28 ml/L)

At 4300 m (SaO2=80%):

3425 ml/min = 25 L/min x (165-28 ml/L)

VO2max = Qmax x (CaO2 – CvO2) (ml/min) (L/min) (ml/L)

. .


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~31% decrease VO2max.

50 %VO2max 73.

Endurance Exercise Performance


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~31% decrease VO2max.

50 %VO2max 50.

150 Wdecreased to

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exercise






Acclimatization Improves Submax Exercise Performance

Performance Metric:Endurance Time at aFixed Work Intensity



Performance Improvement is Strongly Correlated to Ventilatory Acclimatization



Sanctioned Competitions:2010 FIFA World Cup (~5,000 ft)2002 Winter Olympics (4,675 – 5,742 ft)Pikes Peak Marathon (7,000 – 14,110 ft)Leadville 100 (9,200 – 12,600 ft)2014 Winter Olympics (5,000 ft)

Recreational Activities:Trekking & MountaineeringSnow SportsHunting & Fishing

Occupational Activities:Military & Law EnforcementForestry & MiningCivil Engineering

Optimizing Exercise Performance At High Altitude:What’s the fuss?


Altitude Impact on NeuropsychologicalPerformance

Kryskow et al., ASEM, 2013


Altitude Impact on NeuropsychologicalPerformance

Take home message: immediate impairment, but rapid recovery


Summary

1. Biophysics of the Altitude Environment

2. Altitude Acclimatization:

Key Physiological Adaptations

Time-Course

3. High Altitude Stress:

Medical Problems - Altitude Illness

Performance – Physical & Neuropsychological


Questions?

Pikes Peak Sunset

Mt. Kilimanjaro Crater

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