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?

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

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

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

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**

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

Calcium accumulation Ryanodine receptor Fatigue Fig 33-4 - 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

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

Central and Neuromuscular Fatigue Fig 33-5 - illustrates fatigue in ms ulnar nerve stimulation - full stim indicated by ms AP force production absent - ms fatigue EMG - often distinct changes - fatigue Fig 33-6 - 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 33-8 - faster recovery with distraction - “active pauses”

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

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

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

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

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