Biology 350: Biology & Space Exploration

1. Biology 350: Biology & Space Exploration Musculoskeletal Function Col Ronald D. Reed, PhD Professor & Head of Biology U.S. Air Force Academy 1999

2. Learning Objectives 1.Define key terms/concepts 2.Describe muscle structure & function; explain how normal hypertrophy occurs 3. Describe muscle fiber types and how contraction & relaxation occur (isometric vs. isotonic; concentric vs. eccentric) 4. Explain atrophy with disuse or disease on Earth; compare to selective atrophy of spaceflight (muscle types & groups); discuss possible mechanisms 5. Describe the adaptation to different loading conditions on Earth & in microgravity

3. Objectives (cont’d) 6.Describe bone & connective tissue structures 7. Discuss mechanisms linking physical activity/ stress to the maintenance & reformation of bone 8. Explain bone loss in microgravity, including its long-term impacts; relate to hormonal or other changes 9. Explain the role of intervertebral discs in weightbearing and spinal movements; correlate to mechanisms of spinal lengthening and back pain in space 10. Discuss countermeasures and evaluate their effectiveness vs. musculoskeletal changes in space

4. Use It or Lose It !

5. Some mission patches when effects were studied

6. Skeletal Muscle Functions • Exert force to change joint angle • Concentric - muscle shortening • Eccentric - muscle lengthening • Exert force to maintain joint angle - isometric (static tension) • Produce body heat

7. Review of Anatomy • Whole Muscle • Muscle fiber (cell) • Myofibril • Sarcomere • Myofilaments • Myosin • Actin • Cross-bridging & “ratcheting”

8. Binding Site (need Ca2+) Cross-bridge Thin Filament (actin) Z membrane (end of sarcomere) Thick Filament (myosin)

9. Muscle contraction • Coupled reaction: Chem. energy à physical motion ATP hydrolysis à force • é [Ca2+] in cell allows reaction • Slow- & fast-twitch muscle specializations

10. Slow- & Fast-Twitch Muscles Twitch Rate Slow Fast Glycogen Content Low High Glycolytic Capacity Low High Fatigue Resistance High Low Respiration Type Aerobic Anaerobic Capillary Supply High Low Slow-twitch found more in muscles (like postural muscles) that must sustain contractions for long times without fatigue. Depend relatively more on fats for energy.

11. Atrophied Fiber Control Fiber Power (un x ft/s) Force (% of Peak Force)

12. Studies of Rat Hindlimb Muscle, Nerves, Biomechanics, etc. • Focus on antigravity (postural) muscles • Why hindlimb? In mg rats use forelimbs to move in cages; hindlimbs float except for grasping. Also, have Earth model. • Results: • Significant atrophy, ê protein & mass • Shift in major muscle fiber type (ST à FT) • ê capacity to break down certain nutrients & some shift from fat to glycogen use in ST

13. Studies of Rat Hindlimb Muscle, Nerves, Biomechanics, etc. • More Results: • Muscle atrophy in mg not returned to normal in 14 days back on Earth • é susceptibility to damage on return to Earth • Interstitial edema & lesions in sarcomeres developed postflight -- damage • May impair movements linked to antigravity muscle function and/or postural control

14. Some Human Results in Spaceflight • On one 27-day mission: • 10% ê leg muscle volume • 20% ê strength • Negative nitrogen balance(muscle & body) • Highest day #1 (ê food intake) • ê lean body mass, especially calves, & ê strength • Negative phosphate balance • Some é fatiguability (plus, see on landing) • Some evidence reach new steady state with time

15. Motion & Coordination Issues • Rearrange biomechanical nature of moving • Changes relation of body mass & effort • Elimination of static work & ê dynamic work • ê activity of postural-tonic musculature • Few eccentric muscle contractions • No “gravity assist” when lowering objects • No “gravity fighting” posturally • 175-day Russian missions show atrophy leads to increase EMG signal per torque • Formation of new coordination patterns and alteration of the motor activity as a whole

16. Summary of Some Causes for Muscle Changes in mg • Removal of mechanical loads & less work for many muscle groups • Deconditioning of postural muscles • Elimination of foot support • Restructuring of normal motor patterns • Fluid shifts, microcirculatory changes, or altered tissue nutrition?

17. Bones ! • Dynamic, living tissue • Mechanical support • Calcium hemostasis • Strength due to matrix of calcium, phosphorous, and collagen

18. Cells in Bone • Osteoblasts -bone-forming • Osteoctyes - embedded osteoblasts • Osteoclasts - Breakdown bone & release Ca2+

19. Formation or Resorption? • Depends on stress (“?” Effect) & hormones • In space, overall: • Bone demineralization • ê strength & density • Metabolic changes & Ca2+ mobilization • Elevated Ca2+ excretion (I.e., negative calcium balance)

20. Net Calcium Absorption Osteo______? Intestine & Kidney Blood Calcium Bone Osteo______? Net Calcium Blood Factor -blasts -clasts Absorption Calcium Physical Activates Inhibits N/A No Direct Stress Effect Calcitonin ? Inhibits PTH ? Activates

21. Net Calcium Absorption Osteo______? Intestine & Kidney Blood Calcium Bone Osteo______? Net Calcium Blood Factor -blasts -clasts Absorption Calcium Physical Activates Inhibits N/A No Direct Stress Effect Calcitonin ? Inhibits Decreases Down PTH (P­H) ? Activates Increases Up

22. Mechanism of mg Demineralization • Not well known • Removal of gravitational load on the skeleton • Changes in blood flow and metabolism in bones • Changes in hormonal and immune status

23. Bone, Calcium, & Space Flight (Morey-Holton, et al.) • Used young rats in rapid growth stage • Housing affects the response • Animals housed individually showed more in-flight changes & slower readaptation to Earth than animals in group cages • Not all regions of bones or all bones affected • Long bones ê formation on the periosteal surface, but not endosteal surface • No changes in the ribs, vertebra ,or maxilla (jaw), so response is not same everywhere

24. Pathophysiology of Mineral Loss in Space Flight (Arnaud, et al.) • In mg calcium is lost from bones, blood calcium é, & calcium is excreted in the urine. • This study examined changes in the balance of calcium entering and leaving the body. Saw: • é loss of calcium • Parathyroid hormone was ê consistent with response to the é calcium levels

25. The Musculoskeletal System in SpaceNASA video AAV-1543

26. Notes from video: Adaptations to Microgravity • Muscle atrophy • Reduce muscle tone and strength • Increased muscle fatigue • Reprogramming muscle synergism • Reduced motor control • Motor endplate degeneration • Increased contraction velocity • Bone demineralization and redistribution • Connective tissue degeneration • Back pain

27. Cross-bridge Binding Site Thin Filament (actin) Z membrane Thick Filament (myosin)

28. Muscular System Specifics • Does adapt, but have weakness -- possible muscle tears • See muscle atrophy, especially slow-twitch • Decreased tone, strength, & size (regional) • Decreased protein synthesis • Negative nitrogen balance • Increased plasma amino acids • Increased plasma creatinine & 3-methylhistidine

29. Physiological mechanisms that may explain muscle related adaptations associated with microgravity • Loss of static & dynamic loads along longitudinal axis of body • Cephalic fluid shifts

30. Adaptations associated with the skeletal system during microgravity • External forces are decreased • Bone synthesis is reduced • Bone architecture and composition are modified to accommodate the new lower load conditions • Altered calcium metabolism • Reduced bone strength

31. Bone mineral density • Normal changes in overall whole body bone density • Increased 4.2% in skull ! • Bone loss is functional (structural & mineral changes; impacts overall quality) • Calcium loss at rapid rate at first, then continues (plateau?) • Data suggest bone loss occurs at rates of 0.5 - 2.0% / month

32. 2 Mechanical factors affecting bone loss • Changes are regional and function specific • Loading bearing • Muscle pull - Greatest site of mineral loss is at muscle insertion sites

33. Possible physiologic mechanism underlying skeletal deconditioning • Principal stimuli to skeleton are altered • Biomechanical stress • Fluid pressure • Bone redistribution from feet to head during space flight • Cell mechanism unknown

34. Spaceflight (- biomechanical stress/fluid shifts) Skeleton Focal/Regional Calcium/Endocrine + serum Calcium levels - Parathyroid hormone + Serum Phosphorous - 1,25 dihydroxyvitamin D - Intestinal calcium absorption - Calcium balance Resorption > formation Diet Adrenal Activity Calcitonin - Bone Mass + Urinary Calcium Excretion

35. Spinal Changes • Increased height • 68% experience back pain • Possible Factors • Spine unloading • Intervertebral disc swelling • Spinal lengthening • Outer disc annulus and facet joint distension • Spinal ligament stretching • Paraspinal muscle stretching • Nerve root dysfunction

36. Countermeasure for overall musculoskeletal deconditioning • Current countermeasures • Treadmill • Rowing • Bicycle • Current measures time consuming (how much?) & ineffective (why?) • Recovery on Earth also incomplete

37. Potential countermeasures for musculoskeletal deconditioning • Exercise: • Resistive • Aerobic • Human centrifuge • Exercise against LBNP (possibly with counter-pressure suit) • Pharmacologic agents -- e.g.??

38. Benefits of research to Earth • Disease - osteoporosis, muscular dystrophy • Fracture healing • Rehabilitation