Anaerobic Threshold

1. Anaerobic Threshold Does it exist? How is it determined?

2. 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

3. 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)

4. 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

5. 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

6. Buffering of blood pH • Primary blood buffer is bicarbonate H+ + lactate- + Na+ + HCO3- Na+ + lactate- + H2CO3  H2O + CO2

7. Wasserman et al., JAP, 1973

8. New method for detecting AnT by gas exchange(Beaver, Wasserman & Whipp, JAP, 1986) V-slope method criteria • break in linearity of VCO2–VO2 • break in linearity of VE–VO2 • VE/VO2breaks with linearity while VE/VCO2remains constant • PETO2–VO2 begins to rise while PETCO2–VO2is slowly rising or constant • RER–VO2having been flat or rising slowly changes to more positive slope

9. Respiratory compensation point stimulated by pH Ventilatory threshold stimulated by CO2 production

10. Most difficult subject. AnT was detected by only two investigators. AnT points detected by six investigators (multiple vertical lines). Beaver, Wasserman, & Whipp, JAP, 1986)

11. Blood Lactate Accumulation and Removal Effects on Blood Lactate Concentration

12. Lactate Response to Prolonged Exercise(70% of VO2max) (Kolkhorst & Buono, Virtual Exercise Physiology Lab, 2004)

13. Lactate Response to Prolonged Exercise

14. Lactate Response to Incremental Exercise(endurance-trained athlete) (Kolkhorst & Buono, Virtual Exercise Physiology Lab, 2004)

15. Mitochondrial PO2 during exercise 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)

16. 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

17. Effects of epinephrine (EPI) on metabolism •  glycogenolysis •  glycolysis • inhibits lipolysis

18. La and EPI Response to Exercise La EPI

19. 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

20. Metabolic Fate of Lactate

21. 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.

22. Energetic Value of Lactate

23. Lactate Shuttle

24. Cori Cycle

25. 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

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

27. 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

28. Pulse injection tracer technique

29. Continuous infusion tracer technique

30. WHEN YOU ARE IN DEEP TROUBLE, LOOK STRAIGHT AHEAD, KEEP YOUR MOUTH SHUT and SAY NOTHING.

31. 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]

32. 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

33. Rates of blood lactate appearance (Ra) and disappearance (Rd) during graded exercise before and after training Holden et al., JAP, 1992

34. 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)

35. 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

36. Lactate clearance Monocarboxylate transporters (MCTs)

37. Andrew Halestrap, University of Bristol

38. 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

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

40. Prevalence of MCT1 and MCT4 in muscles of different fiber type composition Semimembranosus soleus MCT1 MCT4

41. 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