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.

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?

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

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.

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

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

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

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

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)

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?

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.

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

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

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.

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).

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

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

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

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

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)

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

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

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??

Muscle Temperature Effect on Fatigue Optimal deep muscle temperature between 80 - 86 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

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?

Assignment for next week Read handout deVries & Housh Read Enoka, 2003 pgs. 374-389. Prepare for questions next week over this lecture.

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

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

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.