1. NEUROMUSCULAR FATIGUE
In Exercise Physiology, neuromuscular fatigue can be defined as a transient decrease in muscular performance usually seen as a failure to maintain or develop a certain expected force or power.

2. Importance of Neuromuscular Fatigue
Does O2 delivery alone limit exercise performance?
Is it just O2 transport and O2 fuel utilization?
Have we adequately explored other areas relating to muscle contractile function?
TD Noakes – South Africa
Only 50% of VO2 max trials result in a plateau – is there really a plateau?
Is fatigue biochemical or CNS controlled anticipatory response?

3. Loss of Strength with Fatigue
Any volitional loss of strength during a sustained exercise is the basis of fatigue.

4. Effect of Fatigue on Reflexes and Coordination
A reflex arc is fatigable.
If a reflex arc is stimulated repeatedly – it will eventually fail to elicit any type of expected reflex response.
The more interneurons and synapses involved, the more quickly it may become fatigued.
Coordination can be viewed the same way
Irradiation of motor impulses to neighboring motor nerve centers – coordination is lost.

5. Effect of Fatigue on Industrial Workers
How much work can be done in an 8-hour time period without fatigue?
Static work is more fatiguing than dynamic work
Blood flow
Rest periods

6. Basic Nature of Fatigue
Relationship between intensity of work and endurance appears to be a fundamental characteristic of performance…
Is there some equation that can be universally applied to calculate the highest sustainable workload?
Physical Working Capacity at Fatigue Threshold
PWCFT

7. Central versus Peripheral
Where does fatigue occur?
Central fatigue
Proximal to the motor unit
Peripheral fatigue
Residing within the motor unit

8. Central Fatigue Brain and spinal cord; CNS fatigue
Studies that used voluntary exhaustion and then additional electrical stimulation
After voluntary exhaustion, electrical stimulation evoked sizable force production
Central location of fatigue

9. Peripheral Fatigue
Fatigue occurring within the local motor unit; local fatigue
Studies that fatigued a muscle with electrical stimulation to the point of no muscle twitch
Muscle action potentials were relatively unaffected
Peripheral location of fatigue (but not at the NMJ)

10. So, where does fatigue occur?
In both central and peripheral locations.
The location of fatigue is intensity-dependent
Lower-intensity, longer duration fatigue will primarily occur centrally
Higher-intensity, short duration fatigue will primarily occur peripherally
Example  Why does pedaling rate decrease during the Wingate test?
Example  Why can’t we do another repetition after a 5RM lift?
Example  Why do we slow down during the course of a 1600 m race? Do we slow down?

11. What Causes Fatigue? There are two hypotheses:
The Accumulation hypothesis
The Depletion hypothesis
The origin of fatigue is exercise-dependent and may be due to either accumulation, depletion, or both.

12. Accumulation Hypothesis
There is a buildup of metabolic by-products in the muscle fiber
Lactic acid (lactate)
Hydrogen ions (H+)
Ammonia
Inorganic phosphate
Lactate is the primary marker associated with the accumulation hypothesis
If you exercise at a high enough intensity, H+ accumulation interferes with force production
Applies to maximal exercise for 20 sec  3 minutes

13. Four Factors Associated with the Decrease in Force Production Due to H+ Accumulation
H+ interferes with Ca++ release from the sarcoplasmic reticulum.
H+ interferes with actin-myosin binding affinity
H+ interferes with ATP hydrolysis
H+ interferes with ATP production

14. 1. Ca++ release from the sarcoplasmic reticulum
Lactic acid (H+) accumulation disrupts the release of Ca++ from the sarcoplasmic reticulum, in part, by changing the membrane potential (ICF vs. ECF)
When Ca++ is not released as effectively, less is available to bind with troponin-C.

15. 2. Actin-myosin binding affinity
Actin and myosin do not bind as readily or as “tightly” in an increased acidic cellular environment (i.e., microenvironment).

16. 3. ATP hydrolysis
H+ accumulation decreases the effectiveness of mATPase.
Why?

17. 4. ATP production
H+ accumulation interferes with enzymes that catalyze reactions that produce ATP.
What is the rate limiting step in glycolysis?
Allosteric inhibition:

18. Acid Removal What are the two primary ways to clear H+ accumulation?
Increased blood flow
Buffering
What is the body’s primary blood buffer?

19. Depletion Hypothesis 2 aspects to the depletion hypothesis:
Neural depletion
Depletion of acetylcholine
Depletion of energy substrates
Phosphagen depletion
Glycogen depletion

20. Neural Depletion
Neural fatigue that is caused by a depletion of the stimulatory neurotransmitter ACh.
You can induce neural depletion in an excised muscle, but can this happen in vivo?
Two possible instances where it might have occurred:
East German woman completing the final lap of a marathon
Ironman Triathalon competition in Hawaii (same occurance)

21. Depletion of Energy Substrates
2 aspect of substrate depletion:
Phosphagen depletion
Glycogen depletion

22. Phosphagen Depletion 2 aspects to phosphagen depletion:
Reduction in ATP
Small ATP stores in skeletal muscle
Enough to provide 2 – 3 seconds of maximal muscular contraction
Used quickly
Depletion of phosphocreatine (PC)
Enough PC stored to provide up to 20 – 30 seconds of maximal muscular contraction
Nearly completely depleted during maximal exercise

23. Glycogen Depletion
Glycogen is a polymer of glucose that is created with glycogen synthase
Glycogen is stored in relatively large amounts in skeletal muscle.
About 2,000 kcals of energy stored in the form of glycogen (skeletal muscle)
Where are the two primary locations for glycogen storage in the body?
It takes approximately 100 kcals to run a mile, so we have enough glycogen stored for about 20 miles of running.
Glycogen depletion occurs during long-term activities that are done at a medium to moderate intensity
When this occurs, the body is forced to use alternative energy sources (that are not as powerful as glucose metabolism)
Example: “Hitting the runner’s wall”
What about glycogen supercompensation??

24. Muscle Temperature Effect on Fatigue
Optimal deep muscle temperature between  F
At 103, the endurance time decreased 65%
Due to metabolite accumulation or temperature effects of protein/enzyme function (titration).
At 68, the endurance time decreased 80%
Due to interference with neuromuscular transmission

25. Electromyographic Observations of Fatigue
EMG Amplitude (submaximal workloads)
Increases linearly with exhaustion
PWCFT
EMG Amplitude (maximal workload)
Remains constant or decreases with exhaustion
“Muscle Wisdom” hypothesis
EMG Frequency (max and submax)
Decreases…
Why?

27. Assignment for next week
Read handout
deVries & Housh
Read Enoka, 2003 pgs
Prepare for questions next week over this lecture.

28. Course Projects Pick one of the five neuromuscular disorders:
Parkinsonism
Muscular/Myotonic Dystrophy
Cerebral Palsy
Low Back Pain
Peripheral neuropathy (generic)

29. Course Projects
Give a 50-min lecture on the neuromuscular disorder that you chose
Etiology
Pathology
Common signs / symptoms
How does it affect motor unit function?
Describe how we could investigate this disorder with surface EMG and MMG:
Collect pilot data and report your results on 4 or 5 healthy subjects
Extrapolate your findings to the diseased subjects

30. Course Projects Lectures given on: Choice must be made by next week.
April 18
April 25
May 2
Choice must be made by next week.