1

Environmental Variables vs. Physiological Control

• Environmental variables– Pressure (760 mm-Hg)

• Hyperbaric vs. Hypobaric

– Temperature (22°C)• Hypothermic vs. Hyperthermic

– Gas composition (78% N2, 21% O2)• Hypoxic vs. hyperoxia• Nitrogen saturation

– Gravity (1 x G = 9.8 m/s2)• Hypogravity vs. hypergravity

2

3

High Altitude and Hypoxia

• Oxygen availability drops with altitude– 21% of absolute pressure

– O2 concentration in alveoli is what counts • Water vapor remains constant at 47 mm-Hg

• CO2 partial pressure drops with increased respiration rates

• CO2 and H20 partially displace O2

4

5

• System control – keep arterial O2 high

• Acute compensation for low PO2

– Hypoxic stimulation of arterial chemoreceptors increases respiration rate (i.e., breath faster)

Compensation Mechanisms

6

• Long-term compensation for low PO2

– Chemoreceptor mechanism further increases due to decrease in blood pH (days)

– Increased hematocrit and blood volume (weeks)• RBC production increases via erythropoietin

– PO2 sensed

– produced in kidneys– acts on hematopoietic stem cells

• Blood volume under hormonal control of kidneys

Compensation Mechanisms

7

8

9

10

11

12

• Long-term compensation for low PO2

– Increased diffusion capacity of lungs• Increased capillary volume• Increased lung volume• Increased pulmonary pressure

– Increased capillarity in tissues• Stimulate angiogenesis – growth of new capillaries

– Feedback control in local tissue beds– More effective in young, developing animals/people

Compensation Mechanisms

13

• Native adaptation to high altitude– All the same compensations of

acclimatization plus:• Larger chest cavity• Larger heart, especially right side

• Increased cellular efficiency to use O2

Compensation Mechanisms

14

15

Acute High Altitude Sickness

• Cerebral edema– Hypoxia-induced vasodilatation, high capillary

pressure and edema – bad news.

• Pulmonary edema– Vasoconstriction in pulmonary capillaries leads to

increased blood pressure in open capillaries leading to edema – bad news.

• Breathing oxygen, especially under pressure, can reverse symptoms

16

Microgravity

• Gravity (as any force) can have only two effects

1. Cause loading (usually with deformation)

2. Cause motion

17

Space Flight and Physiological Effects

18

Neurovestibular Effects

• Affects about 50% of astronauts• Symptoms begin around 1 hour – recovery

occurs around 1-3 days• Relates to otolith organs in vestibular

apparatus• Provoked by movements and/or odd

orientations• Re-adaptation to 1G can also be challenging

19

Vestibular Apparatus

20

21

22

Theories on Space Motion Sickness

• Fluid shift – Cephalic blood movement

• Sensory conflict – Visual or somatosensory vs. vestibular cues

• Otolith organ asymmetry – Differences in signal between right and left sides

23

Treatment of Space Motion Sickness

• Screening has proven ineffective

• Training strategies have been studied

• Drug combinations are commonly used– May delay adaptation

• Astronauts must tough it out

24

Spaceflight Bone Loss

• Spaceflight (Unloading): 0.5-2% per month

• Type I Osteoporosis (Post-Menopause): – 20% Tot, 5-7 years, 3-4% per yr.

• Type II Osteoporosis (Age related):– ~1% per year, ongoing

25

Bone Feedback Control System

Bone mechanicalproperties

Strain(Deformation)

Canaliculinetworkresistance

Osteocytes produceNitrous oxide /Prostaglandins

Osteoblasts

ExternalLoads

Hormones /Cytokines

Osteoclasts

+-

Streamingflows and osteocytes deformed

SGPs or direct strain

Hormones /Cytokines

Osteocytes producesclerostin

-

26

Skeletal Response to Exercise

Bon

e de

nsit

y (%

)

0

-40

30

NormalRange

Sedentary ModeratelyActive

Changes only occur with significant habitual changes in activities over several months

Spinal injury, immobolization, bed rest, space flight.

Lazy zone

27

Plasma Calcium Effects• Calcium lost in urine - ~200mg/day• Less calcium absorbed – lost in feces• Plasma calcium increases in-flight

– Is normal shortly after landing– May be at greater risk for kidney stones

• PTH is unchanged or decreased in flight but elevates rapidly post-flight (2x)

• Calcitonin is increased in flight (45%)

28

Femur Mineral Mass

SFSF

D

D

D

16.00

17.00

18.00

19.00

20.00

21.00

22.00

23.00

Flight AEM GC Viv GC

Mas

s (m

g)

Placebo

OPG

29

Elastic Strength

SFSF

SF

D

7

8

9

10

11

12

13

Flight AEM Vivarium

Ela

stic

Str

engt

h (N

)

Placebo

OPG

30

Formation of Cortical Bone: Bone Formation Rate

SF

SF

SF D

SF D

1.00

1.50

2.00

2.50

3.00

3.50

4.00

4.50

5.00

5.50

Flight AEM GC Viv GC

En

.BF

R (

0.0

01

xmm2 /d

ay)

Placebo

OPG

31

Muscle Response to Spaceflight

Astronaut muscle fiber cross sections Before Flight After Flight

From Space Research News, Winter, 2001 Dan Riley, The Medical

College of Wisconsin and Riley et al., 2002

• Without resistive exercise for 2-3 months– Leg muscle cross-sectional area ↓ ~30%– Leg strength ↓ ~50%– Shift occurs from slow to fast fiber types– Back muscles become weak, soft tissues at risk of injury

32

• Similar levels of muscle atrophy occur in mouse (12 days), rat (14 days) and human (17 days) soleus \

• Pattern of atrophy (Type I > Type II) may differ between species

From Fitts, Riley and Widrick, (2000), J Appl Pysiol, 89:823-839.

33

• 5-10 fold increase in expression of MHC-IIx and –IIb in soleus but not plantaris or gastroc

• Similar shift to fast isoforms as seen in other species

AEM Control SF

34

Summary of Muscle Feedback

Muscle Strength (PCSA)

IGF-1

ProteinDegradation

ExternalLoads / Demands

Insulin

Protein Synthesis

Circulating IGF-1

Satellite CellActivation

+

Myostatin

MuscleHypertrophy

MuscleHyperplasia

+

Transduction * Mechanical * Electrical

--

-

-

35

Astronaut Fitness - Muscle

1. Reduce health risks to acceptable limits2. Maximize crew time availability for mission

• ISS crew expected to exercise 2.5 hours/day, 7 days per week– Too much exercise can be a physical and

psychological burden

• Crews should not have to rely on exercise– Crisis or emergency situations

– Injury or illness

36

Sun

Arrive Mars12/16/31

Depart Mars1/25/32

MISSION TIMESOutbound

313 days Stay

40 daysReturn

308 daysTotal Mission

661 days

Depart Earth2/6/31

Arrive Earth11/28/32

Example Short-Stay Mission

Sun

Depart Earth5/11/18

Depart Mars6/14/20

Arrive Earth12/11/20

MISSION TIMESOutbound

180 days Stay

545 daysReturn

180 daysTotal Mission

905 days

Arrive Mars11/7/18

Example Long-Stay Mission

Preserving Astronaut health / fitness is major challenge Credit : John Connolly and Kent JoostenPresentation Title: Human Mars Mission Architectures and TechnologiesMeeting: 1/6/2005 meeting of the Robotic and Human Exploration of Mars Roadmap Committee

Manned Mission to Mars - anAmbitious Objective

37

7.910.90

2

4

6

8

10

12

14

16

US P TS P

So

leu

s W

et M

ass

(mg

)

Muscle Mass

Whole Animal Leg Strength

Hindlimb Suspension Effects

Isolated Muscle Strength

38

22.00

22.50

23.00

23.50

24.00

24.50

25.00

25.50

26.00

26.50

27.00

0 2 4 6 8 10 12 14

Day of Study

Bo

dy

Mas

s (g

ram

s)

US D

US P

TS D

TS P

Myostatin Blockade Total Body Mass

39

15

16

17

18

19

20

21

22

US P US D TS P TS D

Lea

n B

od

y M

ass

(g

) .

0

≈

Myostatin Blockade Lean Body Mass

US > TSP<0.001

D > PP<0.001

40

• Movement shifts from lower to upper body

• Weight of limbs is eliminated

• Neck and hips become flexed

Motor Control

41

• Effects of space flight include– Short term

• Activation of extensor muscles is reduced

– Longer term• Reflexes are affected – Achilles tendon tap

– Magnitude of movement is reduced

– Sensitivity to tap is reduced

– Amplitude of induced electrical response is reduced

– Post-flight• Increased rate of tremors• Time to make postural changes increases 2-3 x

Motor Control

42

43

Factors governing cardiac function and peripheral flow

• Cardiac Contractility (CC) • End Diastolic Volume (EDV) • Heart Rate (HR) • Stroke Volume (SV) • Cardiac Output (CO) • Total Peripheral Resistance (TPR) • Blood Pressure (BP) – Systolic and Diastolic

• Control of cardiac function – intrinsic and extrinsic

44

EDV

CC

SV

HR

TPR

BP

X

COX

X

45

EDV

CC

SV

HR

TPR

BP

X

COX

X

+

+

46

47

SNS PNS

EDV

CC

SV

HR

TPR

BP

Baroreceptors

X

COX

X

-- +

++

+

+

-

-

+

48

Short term response to space flight (post-insertion to days)

• Post Insertion (minutes to hours)– Loss of hydrostatic pressure – Cephalic fluid shift– Heart volume increases– Increased EDV causes decreased HR and

cardiac contractility (CC)– CVP decreases (unexpected response)– Physiological response is comparable to laying

down (or standing on one’s head) in 1-G

49

Short term response to space flight (post-insertion to days)

• Short Duration Response to Microgravity (hours to days) – Fluid shift maintained (facial puffiness,

engorged veins, sinus congestion) – Increased diuresis – Decreased water intake– Loss of blood plasma volume and total body

water– EDV decreases leading to increase in HR over

time

50

51

On Orbit — Fluid Loss• Total loss of fluid from the vascular

and tissue spaces is about 1-2 liters (about a 10% volume change compared to preflight)

Pho

to N

AS

A

Adapted from Lujan and White (1994)

52

Long term adaptation to space flight (weeks to months)

• Continued increase in HR • Decrease in baroreceptor reflex function • Exaggerated response to LBNP (ΔHR) • Cardiac system tends to stabilize • Heart volume decreases (atrophy?)• Heart rhythm disturbances (?)

• Disproportionate loss of red blood cell mass (?)

• Changes in vasculature (peripheral resistance?)– Increased venules and decreased arterioles

53

54

• Erythropoietin is a hormone which stimulates red blood cells production

• The loss of fluid in the plasma concentrates red blood cells

• The body responds by decreasing the erythropoietin level

Anemia of Spaceflight

Normal Erythropoietin Level

Ery

thro

poie

tin L

eve

l

Landing

LaunchMicrogravity

Mission Day

Adapted from Lujan and White (1994)

• Upon landing, when the fluid lost during spaceflight is replaced, the red blood cells are diluted. A 10% decrease in red blood cell count is observed. This causes the phenomena called the “anemia of spaceflight”

• The body responds to this dilution by increasing the erythropoietin level

55

Post Flight Effects / Recovery

• Orthostatic Intolerance (hours)– Fluids shift to lower extremities– EDV decreases causing increased HR– Control of BP may not be adequate – Syncope potential– Weakened leg muscles results in reduced

venous valve blood pumping action

56

Tilt Test

• After 15-90 days of bed rest, orthostatic intolerance is evaluated by suddenly tilting the subject from the supine to the upright position

• Heart rate increases and blood pressure decreases, causing dizziness (pre-syncope) or loss of consciousness (syncope)

• This orthostatic intolerance also occurs in astronauts when they try to stand immediately after spaceflight

Doc

umen

ts M

ED

ES

Pre-syncopal women

Pre-syncopal

men

Non-pre-syncopal

men

100% 20% 80%

Results after 5-16 day missions

57

Syncopy / Pre-syncopy Astronauts

• Low total peripheral resistance before and after space flight

• Strong dependence of standing stroke volume on plasma volume (r=0.91 in pre-syncopal women vs. r=0.17 in non-pre-syncopal men)

• Deficient norepinephrine release response

58

Post Flight Effects / Recovery

• Elevated HR (several days)• Similar to disuse / sedentary effects• Anemic-like conditions after rehydration

(RBC dilution)

• Duration of the recovery period depends on duration of exposure to reduced-gravity

59

Countermeasures to Cardiovascular Deconditioning

• In-flight – Exercise – Lower Body Negative Pressure Device (LBNP)– Russian Chibis (LBNP) and Penguin (elastic load)

suits– Neck cuff (positive or negative pressure)– Thigh cuffs

• Pre-landing – Saline fluid loading – G-suits (positive pressure, lower torso)– Recumbent seating (ISS crew members)

• Post-mission – Exercise, time