Effects of dichloroacetate on V̇O2 and intramuscular 31P metabolite kinetics during high-intensity exercise in humans

Journal of Applied Physiology

Volumn 95, Issue 3, 2003, Pages 1105-1115

  Rossiter, H B ^a,d   Ward, S A ^b   Howe, F A ^a   Wood, D M ^a   Kowalchuk, J M ^c   Griffiths, J R ^a   Whipp, B J ^a,b,e  

^a ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^b UNIVERSITY OF GLASGOW   (United Kingdom)

^c UNIVERSITY OF WESTERN ONTARIO   (Canada)

^d UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^e HARBOR UCLA MEDICAL CENTER   (United States)

Author keywords

Dichloroacetate; Fatigue; Kinetics; Magnetic resonance spectroscopy; O2 uptake; Phosphocreatine concentration

Indexed keywords

ADENOSINE TRIPHOSPHATE; CREATINE PHOSPHATE; DICHLOROACETIC ACID; PYRUVATE DEHYDROGENASE; LACTIC ACID; PHOSPHATE; PYRUVATE DEHYDROGENASE COMPLEX;

ACIDIFICATION; ADULT; ARTICLE; BLOOD SAMPLING; CONFIDENCE INTERVAL; ENERGY TRANSFER; EXERCISE; FATIGUE; HUMAN; HUMAN EXPERIMENT; KINETICS; LACTATE BLOOD LEVEL; MALE; MEASUREMENT; NORMAL HUMAN; OXYGEN CONSUMPTION; PH; PHOSPHORUS NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; QUADRICEPS FEMORIS MUSCLE; RESPIRATORY CHAIN; ALGORITHM; BIOLOGICAL MODEL; BLOOD; DRUG EFFECT; LUNG GAS EXCHANGE; METABOLISM; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PHYSIOLOGY; SKELETAL MUSCLE;

ADENOSINE TRIPHOSPHATE; ADULT; ALGORITHMS; DICHLOROACETATE; EXERCISE; HUMANS; HYDROGEN-ION CONCENTRATION; KINETICS; LACTIC ACID; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MODELS, BIOLOGICAL; MUSCLE, SKELETAL; OXYGEN CONSUMPTION; PHOSPHATES; PHOSPHOCREATINE; PULMONARY GAS EXCHANGE; PYRUVATE DEHYDROGENASE COMPLEX;

EID: 0041922358     PISSN: 87507587     EISSN: None     Source Type: Journal    
DOI: 10.1152/japplphysiol.00964.2002     Document Type: Article

References (55)

1. Allen DG and Westerblad H. Role of phosphate and calcium stores in muscle fatigue. J Physiol 536: 657-665, 2001.
2. 2 uptake at onset of intense exercise in humans. Am J Physiol Regul Integr Comp Physiol 282: R273-R280, 2002.
3. Barstow TJ, Jones AM, Nguyen PH, and Casaburi R. Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise. J Appl Physiol 81: 1642-1650, 1996.
4. Beaver WL, Wasserman K, and Whipp BJ. On-line computer analysis and breath-by-breath graphical display of exercise function tests. J Appl Physiol 34: 128-132, 1973.
5. i disappearance during recovery from muscular exercise. FEBS Lett 269: 402-405, 1990.
6. Burns AH, Summer WR, Burns LA, and Shepherd RE. Inotropic interactions of dichloroacetate with amrinone and ouabain in isolated hearts from endotoxin-shocked rats. J Cardiovasc Pharmacol 11: 379-386, 1988.
7. 2 during heavy exercise. J Appl Physiol 62: 199-207, 1987.
8. Chance B and Williams CM. Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilisation. J Biol Chem 217: 383-393, 1955.
9. Conley KE, Kemper WF, and Crowther GJ. Limits to sustainable muscle performance: interaction between glycolysis and oxidative phosphorylation. J Exp Biol 204: 3189-3194, 2001.
10. Constantin-Teodosiu D, Carlin JI, Cederblad G, Harris RC, and Hultman E. Acetyl group accumulation and pyruvate dehydrogenase activity in human skeletal muscle during incremental exercise. Acta Physiol Scand 143: 367-372, 1991.
11. Gibala MJ and Saltin B. PDH activation by dichloroacetate reduces TCA cycle intermediates at rest but not during exercise in humans. Am J Physiol Endocrinol Metab 277: E33-E38, 1999.
12. 2 on-kinetics in isolated in situ canine muscle. J Appl Physiol 85: 1394-1403, 1998.
13. 2. J Appl Physiol 89: 1293-1301, 2000.
14. Grassi B, Hogan MC, Greenhaff PL, Hamann JJ, Kelley KM, Aschenbach WG, Constantin-Teodosiu D, and Gladden LB. Oxygen uptake on-kinetics in dog gastrocnemius in situ following activation of pyruvate dehydrogenase by dichloroacetate. J Physiol 538: 195-207, 2002.
15. Greenhaff PL, Campbell-O'Sullivan SP, Constantin-Teodosiu D, Poucherã SM, Roberts PA, and Timmons JA. An acetyl group deficit limits mitochondrial ATP production at the onset of exercise. Biochem Soc Trans 30: 275-280, 2002.
16. Hansford RG. Role of calcium in respiratory control. Med Sci Sports Exerc 26: 44-51, 1994.
17. Harris RC, Hultman E, and Nordesjo LO. Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest. Scand J Clin Lab Invest 33: 109-120, 1974.
18. Hibberd MG, Dantzig JA, Trentham DR, and Goldman YE. Phosphate release and force generation in skeletal muscle fibers. Science 228: 1317-1319, 1985.
19. Howlett RA, Parolin ML, Dyck DJ, Hultman E, Jones NL, Heigenhauser GJF, and Spriet LL. Regulation of skeletal muscle glycogen phosphorylase and PDH at varying exercise power outputs. Am J Physiol Regul Integr Comp Physiol 275: R418-R425, 1998.
20. Howlett RA, Heigenhauser JF, Hultman E, Hollidge-Horvat MG, and Spriet LL. Effects of dichloroacetate infusion on human skeletal muscle metabolism at the onset of exercise. Am J Physiol Endocrinol Metab 277: E18-E25, 1999.
21. Howlett RA, Heigenhauser GJF, and Spriet LL. Skeletal muscle metabolism during high-intensity sprint exercise is unaffected by dichloroacetate or acetate infusion. J Appl Physiol 87: 1747-1751, 1999.
22. Jones AM, Carter H, Pringle JS, and Campbell IT. Effect of creatine supplementation on oxygen uptake kinetics during submaximal cycle exercise. J Appl Physiol 92: 2571-2577, 2002.
23. 31P magnetic resonance spectroscopy. J Physiol 535: 901-928, 2001.
24. Kushmerick MJ. Energy balance in muscle activity: simulations of ATPase coupled to oxidative phosphorylation and to creatine kinase. Comp Biochem Physiol B 120: 109-123, 1998.
25. Lamarra N, Whipp BJ, Ward SA, and Wasserman K. Effect of interbreath fluctuations on characterizing exercise gas exchange kinetics. J Appl Physiol 62: 2003-2012, 1987.
26. eq of the creatine kinase reaction and other phosphate hydrolyses and phosphate transfer reactions. J Biol Chem 254: 6528-6537, 1979.
27. Ludvik B, Peer G, Berzlanovich A, Stifter S, and Graf H. Effects of dichloroacetate and bicarbonate on haemodynamic parameters in healthy volunteers. Clin Sci (Lond) 80: 47-51, 1991.
28. McLoughlin P, Popham P, Linton RA, Bruce RC, and Band DM. Use of arterialized venous blood sampling during incremental exercise tests. J Appl Physiol 73: 937-940, 1992.
29. 31P magnetic resonance. J Biol Chem 248: 7276-7278, 1973.
30. Naressi A, Couturier C, Devos JM, Janssen M, Mangeat C, de Beer R, and Graveron-Demilly D. Java-based graphical user interface for the MRUI quantitation package. MAGMA 12: 141-152, 2001.
31. Parolin ML, Spriet LL, Hultman E, Matsos MP, Hollidge-Horvat MG, Jones NL, and Heigenhauser GJF. Effects of PDH activation by dichloroacetate in human skeletal muscle during exercise in hypoxia. Am J Physiol Endocrinol Metab 279: E752-E761, 2000.
32. Poole DC, Ward SA, Gardner GW, and Whipp BJ. Metabolic and respiratory profile of the upper limit of prolonged exercise in man. Ergonomics 31: 1256-1279, 1988.
33. Poole DC, Ward SA, and Whipp BJ. The effects of training on the metabolic and respiratory profile of high-intensity cycle ergometer exercise. Eur J Appl Physiol 59: 421-429, 1990.
34. Poole DC, Schaffartzik W, Knight DR, Derion T, Kennedy B, Guy HJ, Prediletto R, and Wagner PD. Contribution of exercising legs to the slow component of oxygen uptake kinetics in humans. J Appl Physiol 71: 1245-1253, 1991.
35. Putman CT, Jones NL, Lands LC, Bragg TM, Hollidge-Horvat MG, and Heigenhauser GJF. Skeletal muscle pyruvate dehydrogenase activity during maximal exercise in humans. Am J Physiol Endocrinol Metab 269: E458-E468, 1995.
36. Roberts PA, Loxham SJG, Poucher SM, Constantin-Teodosiu D, and Greenhaff PL. The acetyl group deficit at the onset of contraction in ischaemic canine skeletal muscle. J Physiol 544: 591-602, 2002.
37. 31P-MRS on parameter estimation of metabolic responses to exercise in humans. J Physiol 528: 359-369, 2000.
38. Rossiter HB, Ward SA, Kowalchuk JM, Howe FA, Griffiths JR, and Whipp BJ. Effects of prior exercise on oxygen uptake and phosphocreatine kinetics during high-intensity knee-extension exercise in humans. J Physiol 537: 291-303, 2001.
39. 2 uptake between the on- and off-transients of moderate- and high-intensity exercise in humans. J Physiol 541: 991-1002, 2002.
40. i peak. J Appl Physiol 93: 2059-2069, 2002.
41. Roston WL, Whipp BJ, Davis JA, Cunningham DA, Effros RM, and Wasserman K. Oxygen uptake kinetics and lactate concentration during exercise in humans. Am Rev Respir Dis 135: 1080-1084, 1987.
42. Spriet LL and Heigenhauser GJF. Regulation of pyruvate dehydrogenase (PDH) activity in human skeletal muscle during exercise. Exerc Sport Sci Rev 30: 91-95, 2002.
43. Stacpoole PW. The pharmacology of dichloroacetate. Metabolism 38: 1124-1144, 1989.
44. 31P-magnetic resonance spectroscopy studies of nucleated and nonnucleated erythrocytes; time domain data analysis (VARPRO) incorporating prior knowledge can give information on the binding of ADP. Biochim Biophys Acta 1291: 143-148, 1996.
45. Timmons JA, Poucher SM, Constantin-Teodosiu D, Worrall V, Macdonald IA, and Greenhaff PL. Increased acetyl group availability enhances contractile function of canine skeletal muscle during ischemia. J Clin Invest 97: 879-883, 1996.
46. Timmons JA, Gustafsson T, Sundberg CJ, Jansson E, and Greenhaff PL. Muscle acetyl group availability is a major determinant of oxygen deficit in humans during submaximal exercise. Am J Physiol Endocrinol Metab 274: E377-E380, 1998.
47. Veech RL, Lawson JWR, Cornell NW, and Krebs HA. Cytosolic phosphorylation potential. J Biol Chem 254: 6538-6547, 1979.
48. 31P-MRS signals using the variable projection method and prior knowledge. Magn Reson Med 6: 92-98, 1988.
49. Westerblad H, Allen DG, and Lännergren J. Muscle fatigue: lactic acid or inorganic phosphate the major cause? News Physiol Sci 17: 17-21, 2002.
50. Whipp BJ, Ward SA, Lamarra N, Davis JA, and Wasserman K. Parameters of ventilatory and gas exchange dynamics during exercise. J Appl Physiol 52: 1506-1513, 1982.
51. 2 uptake kinetics during heavy exercise. Med Sci Sports Exerc 26: 1319-1326, 1994.
52. Whipp BJ. Domains of aerobic function and their limiting parameters. In: The Physiology and Pathophysiology of Exercise Tolerance, edited by Steinacker JM and Ward SA. New York: Plenum, 1996, chapt. 12, p. 83-89.
53. 2 uptake kinetics during whole body NMR spectroscopy. J Appl Physiol 86: 742-747, 1999.
54. 31P-NMR study. J Appl Physiol 64: 2333-2339, 1988.
55. 31P-nuclear magnetic resonance spectroscopy. Eur J Appl Physiol 69: 465-473, 1994.