Influence of dichloroacetate on pulmonary gas exchange and ventilation during incremental exercise in healthy humans

Respiratory Physiology and Neurobiology

Volumn 168, Issue 3, 2009, Pages 224-229

  Wilkerson, Daryl P ^a   Campbell, Iain T ^b   Blackwell, Jamie R ^a   Berger, Nicolas J ^a   Jones, Andrew M ^a  

^a UNIVERSITY OF EXETER   (United Kingdom)

^b WYTHENSHAWE HOSPITAL   (United Kingdom)

Author keywords

Acid base balance; DCA; Exercise tolerance; Pulmonary gas exchange

Indexed keywords

BICARBONATE; DICHLOROACETIC ACID; LACTIC ACID;

ADULT; ARTICLE; BICARBONATE BLOOD LEVEL; BICYCLE ERGOMETRY; BLOOD PH; CONTROLLED STUDY; DRUG MECHANISM; EXERCISE; EXERCISE TOLERANCE; EXPIRATORY FLOW RATE; HUMAN; HUMAN EXPERIMENT; LACTATE BLOOD LEVEL; LUNG GAS EXCHANGE; LUNG VENTILATION; MALE; NORMAL HUMAN; PRIORITY JOURNAL;

ADULT; BICARBONATES; DICHLOROACETATE; ENERGY METABOLISM; EXERCISE; EXERCISE TOLERANCE; HEART RATE; HUMANS; LACTIC ACID; MALE; OXYGEN CONSUMPTION; PHYSICAL EXERTION; PULMONARY GAS EXCHANGE; PULMONARY VENTILATION; YOUNG ADULT;

EID: 69249228610     PISSN: 15699048     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.resp.2009.07.004     Document Type: Article

References (42)

1. Allen D.G., Lamb G.D., and Westerblad H. Skeletal muscle fatigue: cellular mechanisms. Physiol. Rev. 88 (2008) 287-332
2. 2 uptake at onset of intense exercise in humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282 (2002) R273-280
3. Barstow T.J., Jones A.M., Nguyen P.H., and Casaburi R. Influence of muscle fibre type and fitness on the oxygen uptake/power output slope during incremental exercise in humans. Exp. Physiol. 85 (2000) 109-116
4. Beaver W.L., Wasserman K., and Whipp B.J. A new method for detecting anaerobic threshold by gas exchange. J. Appl. Physiol. 60 (1986) 2020-2027
5. Beaver W.L., Wasserman K., and Whipp B.J. Bicarbonate buffering of lactic acid generated during exercise. J. Appl. Physiol. 60 (1986) 472-478
6. Brooks G.A. Anaerobic threshold: review of the concept and directions for future research. Med. Sci. Sports Exerc. 17 (1985) 22-34
7. Calvert L.D., Shelley R., Singh S.J., Greenhaff P.L., Bankart J., Morgan M.D., and Steiner M.C. Dichloroacetate enhances performance and reduces blood lactate during maximal cycle exercise in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 177 (2008) 1090-1094
8. 2 in a working red muscle in situ. J. Appl. Physiol. 61 (1986) 402-408
9. Davis J.A., Whipp B.J., Lamarra N., Huntsman D.J., Frank M.H., and Wasserman K. Effect of ramp slope on determination of aerobic parameters from the ramp exercise test. Med. Sci. Sports Exerc. 14 (1982) 339-343
10. Grassi B., Hogan M.C., Greenhaff P.L., Hamann J.J., Kelley K.M., Aschenbach W.G., Constantin-Teodosiu D., and Gladden L.B. Oxygen uptake on-kinetics in dog gastrocnemius in situ following activation of pyruvate dehydrogenase by dichloroacetate. J. Physiol. 538 (2002) 195-207
11. 2 availability. J. Appl. Physiol. 86 (1999) 2013-2018
12. 2 supply and demand limitations. J. Appl. Physiol. 97 (2004) 1077-1081
13. Howlett R.A., Heigenhauser G.J.F., Hultman E., Hollidge-Horvat M.G., and Spriet L.L. Effects of dichloroacetate infusion on human skeletal muscle metabolism at the onset of exercise. Am. J. Physiol. 277 (1999) E18-E25
14. Jones A.M., and Carter H. Oxygen uptake-work rate relationship during two consecutive ramp exercise tests. Int. J. Sports Med. 25 (2004) 415-420
15. O2 kinetics following the onset of heavy intensity cycle exercise. Pflugers Arch. 447 (2004) 867-874
16. Jones A.M., Wilkerson D.P., and Campbell I.T. Nitric oxide synthase inhibition with L-NAME reduces maximal oxygen uptake but not gas exchange threshold during incremental cycle exercise in man. J. Physiol. 560 (2004) 329-338
17. O2 kinetics during moderate-intensity cycle exercise. Med. Sci. Sports Exerc. 36 (2004) 1159-1164
18. Kowalchuk J.M., and Scheuermann B.W. Acid-base balance: origin of plasma [H+] during exercise. Can. J. Appl. Physiol. 20 (1995) 341-356
19. Ludvik B., Mayer G., Stifter S., Putz D., Barnas U., and Graf H. Effects of dichloroacetate on exercise performance in healthy volunteers. Pflugers Arch. 423 (1993) 251-254
20. Mateika J.H., and Duffin J. A review of the control of breathing during exercise. Eur. J. Appl. Physiol. Occup. Physiol. 71 (1995) 1-27
21. McKenna M.J., Bangsbo J., and Renaud J.M. Muscle K+, Na+, and Cl disturbances and Na+-K+ pump inactivation: implications for fatigue. J. Appl. Physiol. 104 (2008) 288-295
22. Myers J., and Bellin D. Ramp exercise protocols for clinical and cardiopulmonary exercise testing. Sports Med. 30 (2000) 23-29
23. Palange P., Ward S.A., Carlsen K.H., Casaburi R., Gallagher C.G., Gosselink R., O'Donnell D.E., Puente-Maestu L., Schols A.M., Singh S., and Whipp B.J. Recommendations on the use of exercise testing in clinical practice. Eur. Respir. J. 29 (2007) 185-209
24. 2 and exercise hyperventilation: a critical reappraisal. Respir. Physiol. Neurobiol. 150 (2006) 4-18
25. O2 max in the exercise-trained human quadriceps. J. Appl. Physiol. 86 (1999) 1048-1053
26. Robergs R.A., Ghiasvand F., and Parker D. Biochemistry of exercise-induced metabolic acidosis. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287 (2004) R502-516
27. O2 and intramuscular 31P metabolite kinetics during high-intensity exercise in humans. J. Appl. Physiol. 95 (2003) 1105-1115
28. Spriet L.L., and Heigenhauser G.J. Regulation of pyruvate dehydrogenase (PDH) activity in human skeletal muscle during exercise. Exerc. Sport Sci. Rev. 30 (2002) 91-95
29. Spriet L.L., Howlett R.A., and Heigenhauser G.J. An enzymatic approach to lactate production in human skeletal muscle during exercise. Med. Sci. Sports Exerc. 32 (2000) 756-763
30. Stacpoole P.W., Nagaraja N.V., and Hutson A.D. Efficacy of dichloroacetate as a lactate-lowering drug. J. Clin. Pharmacol. 43 (2003) 683-691
31. Timmons J.A., Poucher S.M., Constantin-Teodosiu D., Worrall V., MacDonald I.A., and Greenhaff P.L. Increased acetyl group availability enhances contractile function of canine skeletal muscle during ischemia. J. Clin. Invest. 97 (1996) 879-883
32. Timmons J.A., Gustafsson T., Sundberg C.J., Jansson E., and Greenhaff P.L. Muscle acetyl group availability is a major determinant of oxygen deficit in humans during submaximal exercise. Am. J. Physiol. 274 (1998) E377-E380
33. Wagner P.D. Determinants of maximal oxygen transport and utilization. Annu. Rev. Physiol. 58 (1996) 21-50
34. Ward S.A. Ventilatory control in humans: constraints and limitations. Exp. Physiol. 92 (2007) 357-366
35. Wasserman K. The anaerobic threshold: definition, physiological significance and identification. Adv. Cardiol. 35 (1986) 1-23
36. Wasserman K., Beaver W.L., and Whipp B.J. Gas exchange theory and the lactic acidosis (anaerobic) threshold. Circulation 81 (1990) 14-30
37. Wasserman K., Whipp B.J., Koyl S.N., and Beaver W.L. Anaerobic threshold and respiratory gas exchange during exercise. J. Appl. Physiol. 35 (1973) 236-243
38. Whipp B.J. Dynamics of pulmonary gas exchange. Circulation 76 (1987) 18-28
39. Whipp B.J., Davis J.A., Torres F., and Wasserman K. A test to determine parameters of aerobic function during exercise. J. Appl. Physiol. 50 (1981) 217-221
40. Whipp B.J., and Ward S.A. Determinants and control of breathing during muscular exercise. Br. J. Sports Med. 32 (1998) 199-211
41. Wilkerson D.P., Koppo K., Barstow T.J., and Jones A.M. Effect of work rate on the functional 'gain' of Phase II pulmonary O2 uptake response to exercise. Respir. Physiol. Neurobiol. 142 (2004) 211-223
42. Wilson J.R., Mancini D.M., Ferraro N., and Egler J. Effect of dichloroacetate on the exercise performance of patients with heart failure. J. Am. Coll. Cardiol. 12 (1988) 1464-1469