It is estimated that 12-20 million people in the United States have obstructive sleep apnea (OSA), a disorder typified by nightly intermittent hypoxia (IH) exposure due to upper airway obstruction during sleep. Epidemiologic, retrospective, and cross-sectional studies have identified associations between OSA and an increased risk for cardiovascular disease, e.g., stroke, ischemic heart disease, and systemic hypertension. There is emerging evidence that IH may be a more potent sympathetic nervous system stimulus than continuous hypoxia (CH), and that the pattern of hypoxia (repetitive or continuous) is a critical factor in determining physiologic response. Prior studies indicate that the episodic reoxygenation that occurs during IH represents an oxidative stress (OS) that causes cellular generation of reactive oxygen species. Additional studies suggest that OS is likely to be influential in the transcriptional activation of specific genes through which hypoxia influences adaptive (or maladaptive) responses. There are major gaps in knowledge regarding the linkage of genomic responses to IH with physiological adaptation. The proposed study represents an initial step in increasing understanding of the physiological importance of episodic periods of IH and CH on selected cardiovascular variables (blood pressure [BP], heart rate [HR]) and the potential modulator roles of OS and Hypoxia-inducible factor-1 alpha (HIF-1alpha) transcription activation. The study will use a within-subjects repeated measures design. Normal subjects will be enrolled to avoid potential confounders due to the underlying disease process. Each subject will participate in three blocks (control, IH, CH). During the IH and CH blocks, BP, HR, exhaled biomarkers (nitric oxide [NO], carbon monoxide [CO]), and circulating biomarkers of HIF-1alpha and heme-oxygenase-1 (target gene controlling cellular generation of CO) will be measured. Statistical analysis will include repeated measures analysis of variance (ANOVA), correlations, and linear regression.
| Rodway, George W; Hoffman, Leslie A; Tasota, Frederick J et al. (2008) Inducing hypoxemia in healthy humans: a method for intermittently lowering arterial blood oxygenation during physiological studies. Wilderness Environ Med 19:218-20 |
| Rodway, George W; Sethi, Jigme M; Hoffman, Leslie A et al. (2007) Hemodynamic and molecular response to intermittent hypoxia (IH) versus continuous hypoxia (CH) in normal humans. Transl Res 149:76-84 |
