Biology 350: Biology & Space Exploration Col Ronald D. Reed, PhD Professor & Head of Biology U.S. Air Force Academy 1999 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 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 Some mission patches when effects were studied 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 Review of Anatomy Whole Muscle Muscle fiber (cell) Myofibril Sarcomere Myofilaments Myosin Actin Cross-bridging & “ratcheting” Binding Site (need Ca2+) Z membrane (end of sarcomere) Cross-bridge Thin Filament (actin) Thick Filament (myosin) Muscle contraction Coupled reaction: Chem. energy physical motion ATP hydrolysis force [Ca2+] in cell allows reaction Slow- & fast-twitch muscle specializations Slow- & Fast-Twitch Muscles Twitch Rate Glycogen Content Glycolytic Capacity Fatigue Resistance Respiration Type Capillary Supply Slow Low Low High Aerobic High Fast High High Low Anaerobic 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. Power (un x ft/s) Atrophied Fiber Control Fiber Force (% of Peak Force) 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, protein & mass Shift in major muscle fiber type (ST FT) capacity to break down certain nutrients & some shift from fat to glycogen use in ST Studies of Rat Hindlimb Muscle, Nerves, Biomechanics, etc. More Results: Muscle atrophy in mg not returned to normal in 14 days back on Earth 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 Some Human Results in Spaceflight On one 27-day mission: 10% leg muscle volume 20% strength Negative nitrogen balance (muscle & body) Highest day #1 ( food intake) lean body mass, especially calves, & strength Negative phosphate balance Some fatiguability (plus, see on landing) Some evidence reach new steady state with time Motion & Coordination Issues Rearrange biomechanical nature of moving Changes relation of body mass & effort Elimination of static work & dynamic work 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 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? Bones ! Dynamic, living tissue Mechanical support Calcium hemostasis Strength due to matrix of calcium, phosphorous, and collagen Cells in Bone Osteoblasts bone-forming Osteoctyes embedded osteoblasts Osteoclasts Breakdown bone & release Ca2+ Formation or Resorption? Depends on stress (“?” Effect) & hormones In space, overall: Bone demineralization strength & density Metabolic changes & Ca2+ mobilization Elevated Ca2+ excretion (I.e., negative calcium balance) Net Calcium Absorption Intestine & Kidney Osteo______? Blood Calcium Bone Osteo______? Factor -blasts -clasts Physical Direct Stress Activates Inhibits Calcitonin PTH Net Calcium Absorption N/A Blood Calcium No Effect ? ? Inhibits Activates Net Calcium Absorption Intestine & Kidney Osteo______? Blood Calcium Bone Osteo______? Factor -blasts -clasts Physical Direct Stress Activates Inhibits Calcitonin PTH (PH) Net Calcium Absorption N/A Blood Calcium No Effect ? ? Inhibits Decreases Activates Increases Down Up 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 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 formation on the periosteal surface, but not endosteal surface No changes in the ribs, vertebra ,or maxilla (jaw), so response is not same everywhere Pathophysiology of Mineral Loss in Space Flight (Arnaud, et al.) In mg calcium is lost from bones, blood calcium , & calcium is excreted in the urine. This study examined changes in the balance of calcium entering and leaving the body. Saw: loss of calcium Parathyroid hormone was consistent with response to the calcium levels The Musculoskeletal System in Space NASA video AAV-1543 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 Cross-bridge Binding Site Z membrane Thin Filament (actin) Thick Filament (myosin) 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 & 3methylhistidine Physiological mechanisms that may explain muscle related adaptations associated with microgravity Loss of static & dynamic loads along longitudinal axis of body Cephalic fluid shifts 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 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 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 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 Spaceflight (- biomechanical stress/fluid shifts) Skeleton Focal/Regional Calcium/Endocrine + serum Calcium levels Resorption > formation - Parathyroid hormone Diet + Serum Phosphorous Adrenal Activity - 1,25 dihydroxyvitamin D Calcitonin - Intestinal calcium absorption - Bone Mass + Urinary Calcium - Calcium balance Excretion 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 Countermeasure for overall musculoskeletal deconditioning Current countermeasures Treadmill Rowing Bicycle Current measures time consuming (how much?) & ineffective (why?) Recovery on Earth also incomplete Potential countermeasures for musculoskeletal deconditioning Exercise: Resistive Aerobic Human centrifuge Exercise against LBNP (possibly with counter-pressure suit) Pharmacologic agents -- e.g.?? Benefits of research to Earth Disease - osteoporosis, muscular dystrophy Fracture healing Rehabilitation