Lecture 6 - Muscle blood flow Flashcards
- what is the role of blood?
- what is the role of heart in blood flow? –> - where is the site of exchange in the muscle fibers?
- what is blood flow? formula?
- exercise has a high what? (related to blood flow ish)
- transport nutrients, oxygen, and hormones to muscle
- pump blood around in body form large to small arteries into capillaries in btw muscle fibers (exchange of nutrients)
- volume of blood travelling through a blood vessel, organ or entire body through time
- BF = volume/time
- high metabolic demand –> high demand in energy
- what happens to blood flow when you exercise?
(1) ?
(2) ? –> leads to what (2)
(1) blood is diverted! more blood in muscles, less blood in gut/kidneys
(2) muscles produce metabolites (ie Co2, lactic acid, K+, ATPs, O2, temp) –> leads to vasodilation of muscles (so more blood into muscle) + vasoconstriction everywhere else! (ie gut kidney) –> if not, vasodilation everywhere and you’re gonna faint bc BP is too low
- blood flow response profile: _________ response of _____ delivery as you increase exercise intensity
- what are the 2 phases? (what does the graph look like?)
- DYNAMIC response of O2 delivery to a step increase in exercise intensity
- minimal blood flow at rest
PHASE 1 = feedforward - BIG spike! than plateaus
- muscle pump
- rapid vasodilation
PHASE 2 = Feedback - starts at 20min ish –> slow increase then plateau
- local metaboliwtes play a role
what is the formula for muscle blood flow?
MBF = (arterial pressure - venous pressure) x MVK
*MVK: Potassium
- what is the muscle pump?
- does it increase or decrease MBF? how?
- thighs and calf muscle act as pump for deep leg vein –> pump between veins and arteries –> become so big that the valve in the vein that usually prevents backflow opens –> blood flows against blood flow (?)
- increases MBF! by increasing pressure gradient between arteries and veins with each muscle contraction
- how does muscle pump operate?
- when is the muscle pump effective/ineffective?
- by increasing pressure gradient btw arteries and veins
- effective when exercising muscle is below heart level –> has blood volume that can be emptied with muscle contraction
- ineffective when exercising muscle is above heart level –> veins are already empty –> arterial-venous pressure gradient cannot be increased
“feedforward” vasodilation
- happens when?
- in proportion to what?
- what is the important concept called?
- immediately present! as soon as you start exercising
- in proportion to muscle activation (tension development & motor unit recuitment
- Flow mediated vasodilation! (FMD)
- what is flow mediated vasodilation caused by? definition
- explain what happens –> leads to 3 things
- by shear stress! stimulus for endothelial production and release of nitric oxide (NO), a potent vasodilator substance
SHEAR STRESS = force of flowing blood on endothelial surface of blood vessel
1) red blood cells rub up against endothelial cells, which stimulates production and release of NO, causing rapid dilation of arterioles: - increase muscle vascular conductance (how easy it is for blood to flow in artery)
- decrease in smooth muscle tone (resistance to blood pressure)
- increase MBF
- what is the other mechanism (other than flow-mediated vasodilation) by which feedforward regulation of O2 delivery during exercise happens?
- explain mechanism
- potassium! released from muscle fibre as part of action potential (neurotransmitters released from motor end plate into synaptic cleft –> make skeletal muscle fibre contract –> potassium in muscle fiber gets released in interstitial space + into blood vessels)
- K+ causes smooth muscle relaxation (causes endothelium to increase dilation)
- released in proportion to muscle activation
what is the formula for MBF?
- what are the 2 components? what are the characteristic/manner of each component?
MBF = delta(P) x MVK
- delta(P): muscle pump! increase delta(P) mechanically!
- MVK: rapid vasodilators –> increase VK chemically
- what are 3 characteristics of phase 2 of muscle blood flow during exercise?
- what is phase 2 called?
- onset delayed
- slower adaptation
- steady-state achieved
Feedback!
what is the metabolic hypothesis of feedback regulation of exercising muscle blood flow?
- when exercising, muscle fiber creates metabolites –> increase concentration of metabolites in muscle –> metabolites go into blood vessesl
- [metabolites] –> “error signal” indicating mismatch btw metabolism and blood flow –> ie don’t have enough metabolites for the amount of blood flow (?)
what does the [metabolites] reflect in feedback regulation of exercising MBF?
it is NOT the metabolites that are being regulated –> rather the [metabolites] reflect the relationship btw O2 demand (metabolism) & O2 supply
feedback regulation of exercising MBF
- what (particularly what) dictates concentration of ___________ in interstitial space = what?
- production: determined by what
- clearance: determined by what?
- what dictates mvt of metabolites into and out of interstitial space
- work rates (and therefore metabolism, particularly anaerobic metabolism) dictates concentration of metabolites in interstitial space = “error signal” from muscle metabolism/MBF mismatch
- PRODUCTION determined by rate of metabolite production (intensity dependant)
- CLEARANCE (of metabolites): determine by muscle blood flow
- metabolite concentration!
- which each muscle contraction, muscle blood flow does what (2) –> what concept?
- explain
(graph)
- MBF increases and decreases with each muscle contraction = feedforward!
- blood flow remains high for a few secs but returns to normal during next few min (feedback)
what causes mechanically induced vs chemically induced endothelial mediated dilation?
MECHANICALLY:
- muscle pump
- conductance
CHEMICALLY:
- potassium
- metabolites
what is the oxygen conforming response?
- refers to the rapid adjustment of force production at a given motor neuron activation (action potential) to match changes in muscle oxygenation
- when muscle __________ is reduced (thus reducing what?), what is also reduced?
- the ______________ response is rapidly abolished upon restoration of what?
- BUT, during exercise, muscle oxygenation is reduced AND force production must be maintained –> then what compensates?
- when muscle perfusion is reduced (thus reducing muscle oxygenation), force production is also reduced –> oxygen-conforming response
- upon restoration of muscle blood flow, oxygen-conforming response is rapidly abolished (?)
- during exercise, motor neuron activation must increase to compensate! –> equals need for greater recruitment and greater metabolite production
during voluntary exercise, humans must (increase/decrease) muscle activation (explain) to maintain a given level of muscle for production/power output when muscle ____ delivery is reduced
- HOWEVER’ this must occur at the expense of disturbances to (2) as well as symptoms of (1)
- increase muscle activation (recruit more and bigger motor units –> recruit more type 2A and 2X fibers for anaerobic metabolism) –> when muscle O2 delivery decreases
- expense of disturbances to muscle metabolic and contractile function (ie accumulation of metabolites leading to fatigue) as well as symptoms of muscular fatigue/discomfort
schéma: how is V’O2 maintained during voluntary exercise when O2 delivery (PcellO2) is reduced? 6 steps
- need ATP to maintain force
- need ADP + Pi + NADH + PcellO2 to make ATP
- decrease O2 delivery (decrease CaO2 and/or BMF) during exercise
- decrease ATP because not enough O2 to meet demand
- increase moto drive in order to maintain force!
- the more we maintain motor drive, the less we have to rely on oxidative phosphorylation –> rely on anaerobic pathways (glycolysis)
what are the effects of decreased PcellO2 on muscle metabolism and contractil function?
- increase glycolysis = increase pyruvate = increase lactate and hydrogen
- increase H+ –> inhibits calcium binding to troponin = inhibits muscle contraction = fatigue - increase inorganic phosphate (from the use of all the ATP)
- Pi causes decrease sarcoplasmic reticulum release of calcium –> decrease myofibrillar calcium sensitivity –> inhibits cross-bridge formation = fatigue
what happens to PCr (% of initial) and Pi (% initial) in the study comparing hyperoxia, normoxia and hypoxia while performing incremental calf plantar flexion exercise? 2 graphs
- hyperoxia can work to the highest watts (12) and longest (23min) vs normoxia (10W, 21min) vs hypoxia (8W, 17min)
- for PCr, levels decrease steadily for everyone, at 7W, hyperoxia at highest, normoxia bit less and hypoxia at 50% Initial PCr
BUT at exhaustion, all 3 groups were at around 45% of initial PCr! - for Pi, levels increase steadily for everyone: at 7W: hyperoxia at lowest, normoxia bit higher and hypoxia the highest
BUT at exhaustion, all 3 groups were around 440 (although hypoxia a bit higher)
- what determines how much [PCr] and [Pi] must change to achieve any given VO2 and muscle power output?
- compared to normoxia, power output achieved (and time to exhaustion) was increased/decreased with hypoxia vs hyperoxia? HOWEVER exhaustion occured at what?
- muscle oxygenation! (PcellO2)
- decreased with hypoxia and increased with hyperoxia –> exhaustion occurred at the same muscle metabolic state across FiO2 trials
a decrease in Pcell O2 will:
- decrease or increase [PCr] and [ADP] ? why?
- decrease or increase [Pi] ? –> consequence?
- decrease or increase [Pi] and [ADP] –> consequence?
- decrease/increase [Pi] and [H+] combine to –> (2)
- as muscle force generating capacity decreases, what must increase? –> will also increase what?
- DECREASE PCr and INCREASE Pi –> to maintain VO2 and power output
- INCREASE Pi –> serves to decrease SR release of Ca, decrease myofribrillar calcium sensitivity and inhibit cross-bridge formation
- INCREASE ADP and Pi –> stimulate glycolysis resulting in a greater rate of pyruvate production than convertion to acetyl-coa by PDH –> resulting in increased production of lactic acid and accumulation of La- and H+
- INCREASE Pi and H+ –> combine to decrease muscle force production and increase rate of developmental skeletal muscle fatigue = performance limitation
- neural drive to the contracting muscles must increase! recruit more and larger motor units to maintain any given power output –> increased ratings of perceived exertion
- why does doing work in hypoxic chamber feel harder?
- do normoxic, hypoxic and hyperoxic conditions lead to the same level of exhaustion?
- because you are actually working harder!
- yes! same level! what changes is how you got there
SUMMARY (again):
- alterations in O2 delivery evoke changes in what?
- during voluntary exercise, what can be increased to maintain muscle force production, at the expense of what?
- which metabolite directly affects muscle contraction function? explain (3)
- which metabolites stimulate glycolysis? –> results in what?
- changes in PcellO2
- motor drive –> albeit at the expense of higher ratings of perceived exertion
- Pi! –> increased [Pi] = decrease SR release of Ca, decrease myofibrillar calcium sensitivity, inhibition of cross-bridge formation
- ADP and Pi stimulate glycolysis –> increase lactic acid production –> onset of blood [La-] accumulation is key “sign post” of impairment to sustainable muscle contractile function = alert sign that you can’t sustain this intensity
other study on 8 trained males –> constant load exercise tests on bike erg –> how was peripheral quadriceps fatigue assessed?
- how was central neural motor drive assessed?
- via changes in pre- vs post-exercise force output in response to supra-maximal magnetic femoral nerve stimulation –> % change (decreased) in quadriceps twist force as a measure of fatigue
- via EMG of vastus lateralis
study #2 found that changes in CaO2 during exercise at a given power output affects what (3)
- explain why?
- rate (magnitude) of peripheral locomotor muscle fatigue development (ie quadriceps muscle force loss)
- amount of neural motor drive required to achieve a given power output
- ratings of perceived muscle fatigue/effort
- is less oxygen, have to increase motor drive (2) to push harder –> creates more metabolites which interferes with muscle function/machinery (1) –> and we feel more exhausted (3) bc we are actually working harder
