Anaerobic Threshold

Does it exist?

How is it determined?

Anaerobic Threshold

How is anaerobic threshold defined?– power just before onset of metabolic acidosis & RER

(Wasserman et al., 1973)

What was/is theoretical basis for anaerobic threshold?– effects on R (RER), lactate formation, VCO2, blood

[bicarbonate] How is anaerobic threshold determined?

– changes in blood [lactate]– ventilatory measures

• RER, VCO2, VE, PETO2 and PETCO2, VE/VO2 and VE/VCO2

Anaerobic threshold: does it existComments by GA Brooks (1985)

Key component of AnT hypothesis is that muscle becomes hypoxic during submaximal exercise– femoral PvO2 did not fall <10 Torr when at 50% of

VO2max (Pirnay et al., JAP, 1972)

– muscle produced La at 10% of VO2max; La production linearly related to work rate; blood flow did not affect La production (Connett et al., Am J Physiol, 1984)

– muscle produces La before blood LT or VT (Green et al., JAP, 1983)

Anaerobic threshold: does it existComments by GA Brooks

VT and AnT occur at same point AnT causes VT– this relationship does not always hold, therefore must

be considered invalid– disassociation of AnT and VT in glycogen-depleted

subjects (Segal & Brooks, JAP, 1979)

– McArdles patients cannot produce La, but still exhibit VT (Hagberg et al., JAP, 1982)

– measuring LT is cheaper (and more accurate) than VT

Control of Ventilation

Ventilatory control is by:– feedback (central and carotid chemoreceptors)– feed forward (central command, muscle feedback)

Redundancy mechanisms control VE VE responds more closely to demands for CO2

clearance than O2 uptake

– ventilation below lactate threshold regulates PaCO2 keeping it at resting levels

Buffering of blood pH

Primary blood buffer is bicarbonate

H+ + lactate- + Na+ + HCO3- Na+ + lactate- + H2CO3 H2O + CO2

Wasserman et al., JAP, 1973

New method for detecting AnT by gas exchange(Beaver, Wasserman & Whipp, JAP, 1986)

V-slope method criteriabreak in linearity of VCO2–VO2

break in linearity of VE–VO2

VE/VO2 breaks with linearity while VE/VCO2 remains constant

PETO2–VO2 begins to rise while PETCO2–VO2 is slowly rising or constant

RER–VO2 having been flat or rising slowly changes to more positive slope

VE vs VO2

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0 1 2 3 4 5 6 7

VO2 (L/min)

VE

(L/m

in)

Ventilatory thresholdstimulated by CO2 production

Respiratory compensation pointstimulated by pH

AnT points detected by six investigators (multiple vertical lines).

Most difficult subject. AnT was detected by only two investigators.

Beaver, Wasserman, & Whipp, JAP, 1986)

Blood Lactate Accumulation and Removal

Effects on Blood Lactate Concentration

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0.5

1.0

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0 30 60 90 120 150 180

Time (min)

La

cta

te (

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Lactate Response to Prolonged Exercise(70% of VO2max)

(Kolkhorst & Buono, Virtual Exercise Physiology Lab, 2004)

Lactate Response to Prolonged Exercise

Lactate Response to Incremental Exercise(endurance-trained athlete)

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0 10 20 30 40 50 60 70 80 90 100

% of VO2max

La

cta

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(Kolkhorst & Buono, Virtual Exercise Physiology Lab, 2004)

Muscle intracellular PO2 and net lactate release. Note that PO2 remains above critical mitochondrial O2 tension (1 torr).

(Richardson et al., 1998)

Relationship between mitochondrial VO2 and PO2. Critical mitochondrial PO2 is around 1.0 torr. (Rumsey et al.,

1990)

Mitochondrial PO2 during exercise

Why does blood lactate increase during heavy exercise?

lactate appearance exceeds lactate removal

evidence does not point to muscle hypoxia

FT recruitment– FT fibers have M-LDH– ST fibers have H-LDH

epinephrine release

Effects of epinephrine (EPI) on metabolism

glycogenolysis glycolysis inhibits lipolysis

La and EPI Response to Exercise

La

EPI

Effect of Altitude on La Response

At altitude: LT occurs at same relative intensity blood [La] higher at same absolute workloads muscle blood flow similar at same absolute workloads EPI threshold occurs earlier at altitude Lactate paradox – peak [La] is less under hypoxic

conditions than at normoxia

Metabolic Fate of Lactate

Reading Assignmentfor Tue, Oct 9

Holden, S-MacRae, SC Dennis, AN Bosch, and TD Noakes. Effects of training on lactate production and removal during progressive exercise in humans. J Appl Physiol 72: 1649-1656, 1992.

-- or --

Stanley, WC, EW Gertz, JA Wisneski, DL Morris, R Neese, and GA Brooks. Systemic lactate turnover during graded exercise in man. Am J Physiol 249 (Endocrinol Metab 12): E595-E602, 1985.

Energetic Value of Lactate

Muscle glycogen (C6)

Palmitic acid (C16)

Glycolysis/ oxidation

2 --

Kreb's Cycle 2 8

Electron Transport Chain

32-34 121

Total 36-38 129

Lactate Shuttle

Cori Cycle

Metabolic Fate of Lactate

During exercise:– ~75% oxidized by heart, liver, and ST fibers

During recovery:– oxidized by heart, ST fibers, and liver (1 fate)– converted to glycogen– incorporated into amino acids– La metabolism depends on metabolic state

Fate of lactate 4 hr after injection under three recovery conditions. Note that oxidation is 1 pathway of removal.

Determining lactate turnover during exercise: tracer methodology

use naturally occurring isotopes– 13C and 2H isotopes most commonly used

pulse injection tracer technique– labeled La added to blood in single bolus– concentration measurements taken over time– rate of concentration decline represents turnover rate

continuous-infusion technique – labeled La added at increasing rate until equilibrium

point is reached, i.e., La appearance = La removal

Pulse injection tracer technique

Continuous infusion tracer technique

WHEN YOU ARE IN DEEP TROUBLE, LOOK STRAIGHT AHEAD, KEEP YOUR

MOUTH SHUT and SAY NOTHING.

Primed continuous-infusion technique(used by Stanley et al. and MacRae et al.)

turnover rate = appearance - disappearance Ra dependent on:

– volume of distribution– arterial [La]

Rd = Ra minus arterial [La] metabolic clearance rate (MCR) = Rd / [La]

– calculates La clearance rate relative to arterial [La]– increasing MCR indicates Rd is dependent on arterial [La]

Lactate response to graded exercise(Stanley et al., JAP, 1985)

Ra and Rd exponentially related to VO2

“linear” relationship between Ra and arterial [La] curvilinear relationship between Rd and arterial [La] MCR decreased at higher work rates

– Rd was slowed as blood [La] increased– Rd is dependent on blood [La]– Rd is function of blood [La] and Ra

Rates of blood lactate appearance (Ra) and disappearance (Rd) during graded exercise before and after training

Holden et al., JAP, 1992

Training adaptations to lactate kinetics(Holden et al., JAP, 1992)

submaximal Ra by training peak Ra similar regardless of training status at same relative intensities, Ra was at <60% and similar at >60% submaximal Rd by training peak Rd regardless of training status at same relative intensities, Rd was similar at <60% and at >60% at same relative intensities, [La]

– at <60% was due primarily to Ra ( EPI and CHO metabolism)– at >60% was due primarily to Rd (lactate shuttle)

Effect of training on blood lactate response

65% pretraining

65% posttraining (same relative workload)

65% posttraining (same absolute workload as 45% pretraining)

45% pretraining

Bergman et al., Am. J. Physiol., 1999

Lactate clearance

Monocarboxylate transporters (MCTs)

Andrew Halestrap, University of Bristol

Monocarboxylate transporters

facilitated diffusion transport of lactate and pyruvate in and out of cells– located on plasma and mitochondrial membrane – reversible transporter– involves H+ transport

MCT1 and MCT4 are major MCT isoforms– MCT1 found more in oxidative fibers– MCT4 found more in glycolytic fibers– at least 8 isoforms of MCTs known in humans

MCT1 in heart is concentrated at the intercalated disks and t-tubules

Semimembranosus soleus

MCT1

MCT4

Prevalence of MCT1 and MCT4 in muscles of different fiber type composition

Monocarboxylate transporters

La transport is essential for muscle pH regulation

MCT activity regulated mostly by La gradient– pH gradients can also increase transport rate

exercise training MCT1, but not MCT4