1. Fatigue During Muscular Exercise
Fatigue- inability to maintain a given exercise intensity
rarely completely fatigued - maintain lower power output
often fatigue identified specifically
other times, diffuse - eg dehydration
several factors disturb homeostasis
easier to identify correlation than causal relationship between factors and fatigue
Compartmentalization - more difficult to identify site of fatigue
eg. ATP depleted at myosin head, but adequate elsewhere?

2. Fatigue Environmental factors - can affect endurance performance
eg. Heat - redistribution of CO
uncouple mitochondria - less ATP with same VO2
inc sweat, heat gain - dehydration - body fluid and electrolyte shifts
affect psychological perception of exercise
glycogen depletion - dec endurance
Metabolite depletion
ATP/ CP - low quantity in cell
must match use with restoration
otherwise - can not maintain exercise

3. 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
why ? - compartmentalization
Down reg / protection theory
ms cell shuts off contraction - with ATP depletion in favor of maintaining ion gradients

4. Fatigue
Free energy of ATP declines 14% in physiological pH range - Fig 2-7
also depends on ATP/ADP ratio
consequence-less energy available for work with given VO2 flux
fatigue also influences ATP binding in X-bridge cycle
Glycogen
depletion associated with fatigue
moderate activity - uniform depletion from different fiber types
low resistance- type I - high type II
Blood Glucose
short intense ex bouts - bld gluc rises
prolonged - bld glucose may fall

5. Metabolite Accumulation
Lactic acid accumulation
short term high intensity exercise
production exceeds removal
strong organic acid - pH decreases
accumulates in blood - exported
muscle acidosis
actually all glycolytic intermediates and ATP breakdown - weak acids
may inhibit PFK - slow glycolysis
may interfere with contraction
may stimulate pain receptors
H+ in blood - CNS - pain, nausea
inhibits O2 / Hb combination in lung
reduces HS lipase - dec FFA oxidation
still unsure if it stops exercise**

6. Metabolite Accumulation
Phosphate and Diprotenated phosph.
With phosphagen depletion - get phosphate accumulation
behaves like proton - PFK inhib
calcium binding interference
Fig 33-3 H2PO42- acid and phosh
indicative of non steady state - fatigue
Calcium Ion
mitochondrial coupling efficiency
some Ca++ stimulates TCA cycle
accumulation - energy to remove
ox phosph uncoupling in test tube
exacerbated by reduced Ca++ sequestering by SR with fatigue

7. Calcium accumulation Ryanodine receptor Fatigue
Fig changes in Ca++ flux and signaling in fatigued muscle
Po - max isometric force
symptoms of fatigue - dec force generation - single or tetanic stim
dec related to SR ca++ release
1. dec free calcium
2. Responsiveness - downward shift
H+ interference with given Ca level
3. Sensitivity - small L-R shift
given free Ca - less force
less impact than dec release or responsiveness

8. Fatigue O2 depletion and Mito density Homeostasis
dec in ms O2 or circ O2 - fatigue
low O2 - indicated by lactate accum or CP depletion (causes of fatigue)
Homeostasis
exercise depends on integration of many functions - any upset -- fatigue
Central and Neuromuscular Fatigue
many sites require adequate functioning - decrement at any --fatigue
possible to have fatigue w/out ms itself being fatigued
eg painful inputs - affect willingness to continue activity

9. Central and Neuromuscular Fatigue
Fig illustrates fatigue in ms
ulnar nerve stimulation -
full stim indicated by ms AP
force production absent - ms fatigue
EMG - often distinct changes - fatigue
Fig inc in EMG signal - failure in muscle to respond
Fig 33-7shift to left - PFS
Power Frequency spectrum
slow fibers recruited at fatigue
Central fatigue - Stechnov Phenomenon
Fig faster recovery with distraction - “active pauses”

10. Fatigue Psychological Fatigue Heart as site of Fatigue
understanding of mechanisms is minimal
training - athletes can learn to minimize influence of afferents
approach performance limits of ms
Heart as site of Fatigue
no direct evidence that heart is site of fatigue
art PO2 maintained, heart gets CO
heart can use lactate or FFA
ECG - no signs of ischemia
if there are - heart disease is indicated
severe dehydration... Cardiac arrhythmia possible

11. VO2 max and Endurance
Relationship between Max O2 consumption and upper limit for aerobic metabolism important
1. VO2 max limited by O2 transport - CO and Art content of O2
2. Vo2 max limited by Resp capacity of contracting ms.
Conclude - VO2 max set by O2 tx
endurance determined by resp capacity
Muscle Mass - influences VO2max
but, at critical mass utilization
VO2 max is independent of ms mass

12. 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 resp capacity
illustrates independence of these factors
Davies - CH 6
Correlation's VO2 and End Cap .74
Ms Resp and Running endurance.92
Training 100% in in ms mito
100 % inc in running endurance
15% inc in VO2 max

13. VO2 and Mito Davies study 2 - iron deficiency
Fig 33-9 restoration of iron
hematocrit and VO2 max responded rapidly and in parallel
ms mito and running endurance - more slowly also in parallel
other experiment
anemic blood replaced with rbc
immediately raised Hb - restored VO2 max to 90%
running endurance was not improved
strongly suggest - VO2 max function of O2 transport
Endurance - more dependant on ms mito capacity

14. 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 33-10a - before fatigue - b after
area under curve representative of [ ] of metabolites
Table 33-1 comparison of values
NMR vs muscle biopsy