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
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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
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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
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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
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• 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