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

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. 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 mm(2) area, p < 0.05). ALLO is associated with improvement in CIH-associated oxidant stress, myocardial dysfunction, and apoptosis in rats.