O2 uptake kinetics in response to exercise: A measure of tissue anaerobiosis in heart failure

Yu Zhang Yong Yu Zhang, K. Wasserman*, K. E. Sietsema, I. Ben-Dov, T. J. Barstow, G. Mizumoto, C. S. Sullivan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Oxygen uptake (V̇O2) reflects the rate of aerobic regeneration of high- energy phosphate compounds (primarily adenosine triphosphate [ATP]). Since lactate increase is thought to result from an inadequate rate of aerobic ATP regeneration, it might be expected that lactate increase would be associated with a delayed attainment of steady state for V̇O2 in response to constant load exercise. Similarly if mitochondrial ATP regeneration during exercise is inadequately supported by O2 transport mechanisms, adenosine diphosphate (ADP) and purine nucleotide by-products, such as hypoxanthine, should increase. This study investigated the relationship between V̇O2 kinetics during exercise and accompanying changes in blood lactate and hypoxanthine values in heart failure patients, as a model of compromised O2 transport. Twenty-five patients with chronic heart failure performed cycle ergometry for 6 min at 25 W and at a work rate midway (50 percent Δ) between their lactic acidosis threshold (LAT) and peak V̇O2. Ventilation and gas exchange were measured breath by breath, and venous lactate, hypoxanthine, norepinephrine, and epinephrine were determined at rest and 2 min after each test. The slow component of V̇O2 kinetics was quantified as the rise in V̇O2 from the third to the sixth minute of exercise (ΔV̇O2 [6-3]). Ten age- and size- matched normal subjects served as control subjects. ΔV̇O2 (6-3) was correlated with the increase in lactate (r=0.71, p<0.001), hypoxanthine (r=0.61, p<0.001), and norepinephrine (r=0.41, p<0.01) but not epinephrine in response to exercise in the heart failure patients. The ΔV̇O2 (6-3) and Δlactate were both greater in the patients than in the control subjects at similar absolute work rates (54±20 and 60 W, respectively). However, the slope of the relationship between ΔLa and ΔV̇O2 (6-3) for the patient and normal groups was indistinguishable. The lactate increase was correlated with hypoxanthine increase (r=0.66, p<0.001), but not norepinephrine or epinephrine. In summary, V̇O2 kinetics in response to exercise reflects delayed attainment of the steady state in heart failure patients, which is correlated with increases in lactate and hypoxanthine, markers of increased anaerobic metabolism.

Original languageEnglish
Pages (from-to)735-741
Number of pages7
JournalChest
Volume103
Issue number3
DOIs
StatePublished - 1993
Externally publishedYes

Funding

FundersFunder number
Ciba-Geigy Pharmaceutical Co.
National Center for Research ResourcesM01RR000425
U.S. Public Health ServiceHL 11907, M01 RR 00425

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