Sleep and Breathing

, Volume 14, Issue 1, pp 51–57

Effects of allopurinol on cardiac function and oxidant stress in chronic intermittent hypoxia

  • Antoinette L. Williams
  • Ling Chen
  • Steven M. Scharf
Original Article

DOI: 10.1007/s11325-009-0279-x

Cite this article as:
Williams, A.L., Chen, L. & Scharf, S.M. Sleep Breath (2010) 14: 51. doi:10.1007/s11325-009-0279-x

Abstract

Rationale

Obstructive sleep apnea is associated with left ventricular (LV) dysfunction, oxidant stress, and chronic intermittent hypoxia (CIH). Allopurinol (ALLO) is a xanthine oxidase inhibitor that also scavenges free radicals.

Objectives

Using an animal model of CIH we hypothesized that ALLO decreases oxidant stress and cardiac injury.

Materials and methods

Rats were exposed to either CIH (nadir 4–6%, approximately once per minute) or room air (handled controls, HC) for 8 h a day for 10 days. Four treatment groups (six to ten animals per group) were studied: CIH/ALLO, CIH/placebo (PLAC), HC/ALLO, and HC/PLAC. Outcomes included myocardial lipid peroxides (LPO) for oxidant stress, fraction shortening of the LV cavity for cardiac function (LVFS) and an assay for myocyte apoptosis.

Results

LPO was lower in CIH/ALLO group compared to CIH/PLAC (179 ± 102 vs. 589 ± 68 mcg/mg protein, p < 0.05). LVFS was greater in ALLO animals than PLAC in both CIH and HC (CIH/ALLO 48.6 ± 2.3% vs. CIH/PLAC 38 ± 1.4%; HC/ALLO 64.9 ± 1.8% vs. HC/PLAC 51.5 ± 1.5%; both p < 0.05). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed fewer apoptotic nuclei in LV myocardium in CIH/ALLO compared to CIH/PLAC (38.0 ± 1.4 vs. 48.6 ± 2.3 positive nuclei per 2.5 mm2 area, p < 0.05).

Conclusion

ALLO is associated with improvement in CIH-associated oxidant stress, myocardial dysfunction, and apoptosis in rats.

Keywords

Obstructive sleep apneaOxidative stressAllopurinolMyocardial functionApoptosisIntermittent hypoxiaCardiac functionLeft ventricular dysfunction

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Antoinette L. Williams
    • 2
  • Ling Chen
    • 1
  • Steven M. Scharf
    • 1
    • 3
  1. 1.Division of Pulmonary and Critical Care Medicine, Department of MedicineUniversity of MarylandBaltimoreUSA
  2. 2.Department of MedicineUniversity of South Carolina School of MedicineColumbiaUSA
  3. 3.Sleep Disorders CenterUniversity of MarylandBaltimoreUSA