Fatigue

1. Fatigue • Brooks Ch 33 • Outline • Definitions • Central Fatigue • Peripheral Fatigue • Exhaustion (depletion) Hypothesis • Phosphagens • Glycogen / glucose • Accumulation Hypothesis • pH • Phosphate • Calcium • Potassium (Foss p 65) • Oxygen • VO2max and endurance

2. Fatigue During Exercise • Fatigue- inability to maintain a given exercise intensity • rarely completely fatigued - can maintain lower intensity output • Studied with EMG and observation of contractile function with electrical (nerve) or magnetic stimulation(cortex) • Observe reduction in force and velocity and a prolonged relaxation time • The effect of exercise at an absolute or relative exercise intensity will be more severe on an untrained individual • Causes of muscle fatigue have been classified into central and peripheral • Central - includes CNS, motivation and psychological factors • restoration of force with external stimulation of muscle -indicates central fatigue • NH3, hypoglycemia, reticular formation • Peripheral - PNS to muscle - EC coupling, energy supply and force generation

3. Identifying site of Fatigue • fatigue can be identified specifically - eg. Glycogen, Ca++ depletion • Compartmentalization within the cell increases the difficult of determining the source of fatigue • eg. ATP may be depleted at the myosin head, but adequate elsewhere in the cell - is this detectable? • Often the origin of fatigue is diffuse • eg dehydration • several factors then contribute to a disturbance of homeostasis • Often easier to identify correlations to fatigue, rather than causal contributions to fatigue

4. Environment and Fatigue • Heat and humidity - can affect endurance performance • inc sweat, heat gain, dehydration, changes in electrolytes results in • redistribution of Cardiac Output • Uncoupling of mitochondria - less ATP with same VO2 • changes in psychological perception of exercise • Fatigue is cumulative over time • dehydration yesterday can influence performance today • Glycogen depletion cumulative as well • Reduced circulation to muscle may result in glycogen depletion • Reducing endurance capacity

5. Central Fatigue • possible to have fatigue w/out the muscles itself being fatigued • eg pain may affect drive to continue • Compare force output during fatigue with force output during maximal external stimulus • An ability of this external stimulation to restore force would indicate central fatigue • Central fatigue - Stechnov Phenomenon • Fig 33-8 - faster recovery of strength with distraction or “active pauses” during recovery from exhaustion • Psychological Fatigue • understanding is minimal • With training - athletes can learn to minimize influence of sensory inputs • Able to approach performance limits

6. Peripheral Fatigue • Fig 33-5 - ulnar stimulation is constant - force development decrease - peripheral • Fig 33-6 - large increase in EMG signal - no increase in force - peripheral fatigue • Two hypothesis for peripheral fatigue • a) Exhaustion - depletion of energy substrates - eg ATP, CP, glycogen • Phosphagens are present in low quantities • Must match use with restoration from other metabolic pathways - or fatigue • b) Accumulation of metabolic byproducts - eg H+, NH3, Pi • Likely a combination of factors from both. Contributions of factors are influenced by the specific conditions of the activity

7. Exhaustion Hypothesis • Depletion of metabolites • Phosphagens • Fig 33-1a - CP levels decline in two phases - drop rapidly, then slowly • both severity of first drop and extent of final drop related to work intensity - • fig 33-2 • fatigue - in super-max cycling - coincides with CP depletion in ms • tension development related to CP level - therefore CP related to fatigue • Fig 33-1b - ATP well maintained • compartmentalization? • Down regulation / protection theory? • ms cell shuts off contraction - with ATP depletion in favor of maintaining ion concentration gradients and cell viability

8. Depletion (continued) • Glycogen • depletion associated with fatigue • moderate activity - uniform depletion from different fiber types • Also activity specific fiber depletion • Carbohydrate loading can improve performance • Caffeine (inc FFA mobilization) can also offset fatigue • Blood Glucose • During short intense exercise bouts - blood glucose rises • With prolonged activity- blood glucose may fall • Anapleurotic substrates • Krebs cycle intermediates - decline results in reduced capacity of Krebs

9. Accumulation Hypothesis • H+ (acidity) • Lactic acid accumulates during short term high intensity exercise • As production exceeds removal • exported into blood from muscle • As it is a strong acid -blood pH decreases • H+ in blood - affects CNS • pain, nausea, discomfort, disorientation • inhibits O2 / Hb combination in lung • reduces HS lipase - dec FFA oxidation • **still unsure if this induces fatigue** • muscle acidosis • all glycolytic intermediates are weak acids • ATP breakdown also produces H+ • may inhibit PFK - slowing glycolysis • may interfere with calcium binding TnC • may stimulate pain receptors

10. Accumulation • Phosphate( Pi) and Diprotenated phosphate (H2PO4) • phosphagen depletion (CP) - results in Pi accumulation • behaves like proton • inhibiting PFK • interfering with X-bridge attachment • Fig 33-3 H2PO42- acid and Pi • indicative of non steady state - fatigue • Calcium Ion Accumulation • mitochondrial coupling efficiency • some Ca++ stimulates Krebs cycle • accumulation - requires energy to remove the calcium • Creates oxidative phosphorylation uncoupling in test tube • exacerbated by reduced Ca++ sequestering by SR with fatigue

11. Calcium (cont) • Fig 33-4 - changes in Ca++ flux and signaling in fatigued muscle • Po refers to max isometric force • symptoms of fatigue • decreased force generation - with single or tetanic stimulation • related to SR Ca++ release, and/or pH affects on opening of SR channels • 1. dec free calcium • May be EC coupling at sarcolemma, T tubules, or SR channels • Accumulation in mito, dec SR uptake • 2. Responsiveness - downward shift • H+ interference with Ca++ binding • 3. Sensitivity - small L-R shift • given free Ca++ - less force • less impact than dec release or responsiveness

12. Potassium (K+) • Foss p 65 • K+ is released from contracting muscle resulting in • reducing cytosolic and an increasing plasma K+ content • Release high enough to block nerve transmission in T tubules • Concomitant increase in Na+ intracellulary disrupts normal sarcolemmal membrane potential and excitability • High Na+/K+ pump activity improves performance • Rapid recovery of K+- 2-5 minutes • Complete in ~30 minutes • During exercise inactive tissues take up K+

13. O2 depletion and Mitochondria • O2 depletion and Mito density • dec in ms O2 or circ O2 can lead to fatigue eg - altitude, circulation impairments • low O2 often indicated by lactate accumulation, CP depletion or both • exercise depends on integration of many functions - any upset -- fatigue • Doubling of oxidative capacity with training • increases use of FFA -sparing glycogen • Minimizes impact of the damaging effects of free radicals

14. Heart Fatigue • Heart as site of Fatigue • no direct evidence that heart is site of fatigue • Arterial PO2 is maintained during exercise, heart gets CO priority • heart can utilize lactate or FFA • ECG - no signs of ischemia at maximal effort or fatigue • if there are signs- heart disease is indicated • With severe dehydration... Cardiac arrhythmia is possible

15. VO2 max and Endurance • Relationship between Max O2 consumption and upper limit for aerobic metabolism is important • Two possibilities - • 1. VO2 max limited by O2 transport • CO and Arterial content of O2 • 2. VO2 max limited by Respiratory capacity of contracting ms. • Conclude - • VO2 max set by O2 transport capacity • endurance determined by respiratory capacity of muscle • Evidence • Muscle Mass used- influences VO2max • Minimum of 50% of total ms mass for true value of VO2 max • but, at critical muscle mass VO2 max is independent of muscle mass

16. Muscle Mitochondria • Correlation observed between VO2 max and Mito activity - 0.8 • Henriksson - observed changes in ms mito and VO2 with Tx and detraining • ms mito inc 30%, VO2 19% • VO2 changes more persistent with detraining than respiratory capacity • illustrating independence of these factors • Davies - CH 6 - Correlation's • VO2 and End Cap .74 • Ms Resp and Running endurance.92 • Training 100% increase in ms mito • 100 % inc in running endurance • 15% inc in VO2 max • Again illustrating independence of VO2 max and endurance

17. VO2 and Mito • Davies study 2 - iron deficiency • Fig 33-9 restoration of iron in diet • hematocrit and VO2 max responded rapidly and in parallel • ms mito and running endurance - more slowly, but also in parallel • further experiments • anemic blood replaced with healthy blood containing red blood cells • immediately raises Hb - and restores VO2 max to 90% of pre anemic levels • running endurance was not improved • strongly suggest - VO2 max function of O2 transport • Endurance - more dependant on ms mito capacity

18. Future of Fatigue • Technology is making available new devices - further investigation of fatigue • NMR • possible to determine [ ] of Phosphagens, protons, water, fat, metabolites • without breaking the skin • Fig 33-10 • a at rest - before fatigue • b after fatigue • area under curve representative of [ ] of metabolites (ATP, CP, Pi) • Clear indication of declines and accumulations at fatigue • Table 33-1 comparison of values • NMR vs muscle biopsy