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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? 1 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 2 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 3 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 4 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** 5 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 6 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 7 Fatigue • O2 depletion and Mito density – 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 8 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” 9 Fatigue • Psychological 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 10 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 11 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 12 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 13 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 14