Chest
Volume 122, Issue 5, November 2002, Pages 1686-1694
Journal home page for Chest

Clinical Investigations: Sleep and Breathing
Tissue Hypoxia in Sleep Apnea Syndrome Assessed by Uric Acid and Adenosine

https://doi.org/10.1378/chest.122.5.1686Get rights and content

Study objective

Although the overnight increase in urinary uric acid/creatinine ratio (ΔUA/Cr) is considered by some to be a marker of tissue hypoxia in patients with obstructive sleep apnea-hypopnea syndrome (OSAS), this index is not universally accepted. The purpose of this study was to confirm the validity of ΔUA/Cr as a marker of tissue hypoxia by measuring the plasma level of adenosine during sleep, and also to test the hypothesis that the heart rate (HR) response to apnea is a determinant of tissue hypoxia.

Design

Intergroup comparative study.

Setting

A university hospital, Sapporo, Japan.

Patients

Eighteen patients with OSAS who had apnea-associated, moderate-to-severe arterial desaturation. The patients were classified into two groups: the ΔUA/Cr-positive group, who were considered to have tissue hypoxia, and the ΔUA/Cr-normal group, who were not.

Measurements and results

Although there were no significant differences between two groups of the patients in either arterial desaturation parameters or the apnea-hypopnea index, the plasma level of adenosine during sleep was significantly higher in the ΔUA/Cr-positive group than in the ΔUA/Cr-normal group. Successful treatment with nasal continuous positive airway pressure significantly decreased both ΔUA/Cr and the plasma level of adenosine only in the ΔUA/Cr-positive group. The magnitude of the HR increase after the termination of apnea was significantly smaller in the ΔUA/Cr-positive group.

Conclusions

ΔUA/Cr is a marker of tissue hypoxia, which does not necessarily parallel arterial desaturation indexes in OSAS. Intersubject variability in the HR response to apnea may explain the discrepancy between tissue hypoxia and arterial desaturation indexes.

Section snippets

Subjects

Eighteen adult male subjects with OSAS diagnosed by standard polysomnography were recruited for this study. Inclusion criteria of subjects for this study were as follows: the apnea-hypopnea index (AHI) was > 15/h, the minimum Sao2 was < 80%, and the percentage of time with Sao2 < 90% was > 5%. We excluded the subjects who had gout, diabetes mellitus requiring medication, and renal dysfunction assessed by the serum level of creatinine.

Of 18 subjects, 4 subjects had diabetes mellitus that was

Results

The value of ΔUA/Cr in the 18 subjects widely varied from − 60.8 to 58.3% (mean, − 6.1 ŷ 7.5%). Of them, nine subjects were classified into the ΔUA/Cr-positive group, and the other nine subjects were classified into the normal group (Fig 2). The data obtained from 12 control subjects are also illustrated as individual mean values in Figure 2.

There were no significant differences between the two groups in age, body mass index, and the plasma level of uric acid. Unexpectedly, there were no

Discussion

In this study, we demonstrated that the index of ΔUA/Cr did not parallel the severity of the AI or arterial oxygen desaturation, but was significantly linked to the plasma level of adenosine, which is considered to be another marker of tissue hypoxia, in patients with OSAS. These data indicate that both indexes of ΔUA/Cr and plasma adenosine during sleep reflect the same purine catabolic pathway associated with tissue hypoxia in these patients. We further demonstrated that the intersubject

References (41)

  • R Rubio et al.

    Regulation of coronary blood flow

    Prog Cardiovasc Dis

    (1975)
  • M Bonsignore et al.

    The cardiovascular effects of obstructive sleep apnoeas: analysis of pathogenic mechanisms

    Eur Respir J

    (1994)
  • F Sato et al.

    Heart rate during obstructive sleep apnea depends on individual hypoxic chemosensitivity of the carotid body

    Circulation

    (1997)
  • J Ringler et al.

    Hypoxemia alone does not explain blood pressure elevations after obstructive apneas

    J Appl Physiol

    (1990)
  • M Kamba et al.

    Cerebral metabolism in sleep apnea: evaluation by magnetic resonance spectroscopy

    Am J Respir Crit Care Med

    (1997)
  • MH Jensen et al.

    Urinary loss of oxypurines in hypoxic premature neonates

    Biol Neonate

    (1980)
  • D Sorlie et al.

    Release of hypoxanthine and phosphate from exercising human legs with and without arterial insufficiency

    Acta Med Scand

    (1982)
  • RA Harkness et al.

    Purine transport and metabolism in man: the effect of exercise on concentrations of purine bases, nucleosides and nucleotides in plasma, urine, leukocytes and erythrocytes

    Clin Sci

    (1983)
  • Y Hellsten et al.

    Adenosine concentration in the interstitium of resting contracting human skeletal muscle

    Circulation

    (1998)
  • DA MacLean et al.

    Systemic hypoxia elevates skeletal muscle interstitial adenosine levels in humans

    Circulation

    (1998)
  • Cited by (68)

    • Snoring and napping independently increased the serum uric acid levels and hyperuricemia risk: The Henan Rural Cohort Study

      2022, Nutrition, Metabolism and Cardiovascular Diseases
      Citation Excerpt :

      Some main hypotheses were that habitual snoring is usually accompanied by OSA. First, OSA-induced hypoxemia can cause a rise in adenosine triphosphate (ATP) degradation which eventually increases purine concentrations, leading to elevated blood uric acid levels [34]. Second, excretion of lactic acid, generated during the hypoxic episodes in OSA, could result in higher renal reabsorption of uric acid [35].

    View all citing articles on Scopus

    This study was supported by Research Grant for the Intractable Diseases from the Ministry of Health and Welfare, Japan, and Science Research grant No. 04670451 from the Ministry of Education, Science, Sports and Culture, Japan.

    Dilazep was a gift of Kowa Co. Ltd.

    View full text