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1 Environmental Variables vs. Physiological Control Environmental variables –Pressure (760 mm-Hg) Hyperbaric vs. Hypobaric –Temperature (22°C) Hypothermic.

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Presentation on theme: "1 Environmental Variables vs. Physiological Control Environmental variables –Pressure (760 mm-Hg) Hyperbaric vs. Hypobaric –Temperature (22°C) Hypothermic."— Presentation transcript:

1 1 Environmental Variables vs. Physiological Control Environmental variables –Pressure (760 mm-Hg) Hyperbaric vs. Hypobaric –Temperature (22°C) Hypothermic vs. Hyperthermic –Gas composition (78% N 2, 21% O 2 ) Hypoxic vs. hyperoxia Nitrogen saturation –Gravity (1 x G = 9.8 m/s 2 ) Hypogravity vs. hypergravity

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3 3 High Altitude and Hypoxia Oxygen availability drops with altitude –21% of absolute pressure –O 2 concentration in alveoli is what counts Water vapor remains constant at 47 mm-Hg CO 2 partial pressure drops with increased respiration rates CO 2 and H 2 0 partially displace O 2

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5 5 System control – keep arterial O 2 high Acute compensation for low PO 2 –Hypoxic stimulation of arterial chemoreceptors increases respiration rate (i.e., breath faster) Compensation Mechanisms

6 6 Long-term compensation for low PO 2 –Chemoreceptor mechanism further increases due to decrease in blood pH (days) –Increased hematocrit and blood volume (weeks) RBC production increases via erythropoietin –PO 2 sensed –produced in kidneys –acts on hematopoietic stem cells Blood volume under hormonal control of kidneys Compensation Mechanisms

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12 12 Long-term compensation for low PO 2 –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 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 O 2 Compensation Mechanisms

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15 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 16 Microgravity Gravity (as any force) can have only two effects 1.Cause loading (usually with deformation) 2.Cause motion

17 17 Space Flight and Physiological Effects

18 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 19 Vestibular Apparatus

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22 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 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 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 25 Bone Feedback Control System Bone mechanical properties Strain (Deformation) Canaliculi network resistance Osteocytes produce Nitrous oxide / Prostaglandins Osteoblasts External Loads Hormones / Cytokines Osteoclasts + - Streaming flows and osteocytes deformed SGPs or direct strain Hormones / Cytokines Osteocytes produce sclerostin -

26 26 Skeletal Response to Exercise  Bone density (%) Normal Range Sedentary Moderately Active  Changes only occur with significant habitual changes in activities over several months Spinal injury, immobolization, bed rest, space flight. Lazy zone

27 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 28 Femur Mineral Mass SF D D D FlightAEM GCViv GC Mass (mg) Placebo OPG

29 29 Elastic Strength

30 30 Formation of Cortical Bone: Bone Formation Rate SF SF D FlightAEM GCViv GC En.BFR (0.001xmm 2 /day) Placebo OPG

31 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 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:

33 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 34 Summary of Muscle Feedback Muscle Strength (PCSA) IGF-1 Protein Degradation External Loads / Demands Insulin Protein Synthesis Circulating IGF-1 Satellite Cell Activation + Myostatin Muscle Hypertrophy Muscle Hyperplasia + Transduction * Mechanical * Electrical    - 

35 35 Astronaut Fitness - Muscle  Reduce health risks to acceptable limits  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 36 Sun  Arrive Mars 12/16/31 Depart Mars 1/25/32 MISSION TIMES Outbound313 days Stay40 days Return308 days Total Mission661 days Depart Earth 2/6/31 Arrive Earth 11/28/32 Example Short-Stay Mission Sun  Depart Earth 5/11/18 Depart Mars 6/14/20 Arrive Earth 12/11/20 MISSION TIMES Outbound180 days Stay545 days Return180 days Total Mission905 days Arrive Mars 11/7/18 Example Long-Stay Mission Preserving Astronaut health / fitness is major challenge Credit : John Connolly and Kent Joosten Presentation Title: Human Mars Mission Architectures and Technologies Meeting: 1/6/2005 meeting of the Robotic and Human Exploration of Mars Roadmap Committee Manned Mission to Mars - an Ambitious Objective

37 US P TS P Soleus Wet Mass (mg) Muscle Mass Whole Animal Leg Strength Hindlimb Suspension Effects Isolated Muscle Strength

38 38 Myostatin Blockade Total Body Mass

39 39 Myostatin Blockade Lean Body Mass US > TS P<0.001 D > P P<0.001

40 40 Movement shifts from lower to upper body Weight of limbs is eliminated Neck and hips become flexed Motor Control

41 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 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 44 EDV CC SV HR TPR BP X CO X X

45 45 EDV CC SV HR TPR BP X CO X X + +

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47 47 SNSPNS EDV CC SV HR TPR BP Baroreceptors X CO X X

48 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 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

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51 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) Photo NASA Adapted from Lujan and White (1994)

52 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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54 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 Erythropoietin Level Landing Launch Microgravity 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 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 56 Tilt Test After 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 Documents MEDES Pre- syncopal women Pre- syncopal men Non-pre- syncopal men 100%20%80% Results after 5-16 day missions

57 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 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 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


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