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 mm(2) area, p < 0.05). CONCLUSION: ALLO is associated with improvement in CIH-associated oxidant stress, myocardial dysfunction, and apoptosis in rats.
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 mm(2) area, p < 0.05). CONCLUSION: ALLO is associated with improvement in CIH-associated oxidant stress, myocardial dysfunction, and apoptosis in rats.
Authors: Ling Chen; Jin Zhang; Tracey X Gan; Ye Chen-Izu; Jeffrey D Hasday; Morris Karmazyn; C William Balke; Steven M Scharf Journal: J Appl Physiol (1985) Date: 2007-11-15
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