Effects of allopurinol on cardiac function and oxidant stress in chronic intermittent hypoxia
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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.
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.
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).
ALLO is associated with improvement in CIH-associated oxidant stress, myocardial dysfunction, and apoptosis in rats.
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- Effects of allopurinol on cardiac function and oxidant stress in chronic intermittent hypoxia
Sleep and Breathing
Volume 14, Issue 1 , pp 51-57
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Obstructive sleep apnea
- Oxidative stress
- Myocardial function
- Intermittent hypoxia
- Cardiac function
- Left ventricular dysfunction
- Industry Sectors
- Author Affiliations
- 2. Department of Medicine, University of South Carolina School of Medicine, Columbia, SC, USA
- 1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland, Baltimore, MD, 21201, USA
- 3. Sleep Disorders Center, University of Maryland, 685 West Baltimore St. MSTF 800, Baltimore, MD, 21201-1192, USA