Autonomic dysregulation as a basis of cardiovascular, endocrine, and inflammatory disturbances associated with obstructive sleep apnea and other conditions of chronic hypoxia, hypercapnia, and acidosis.
Obstructive sleep apnea has traditionally been viewed as a structural disease. A multitude of systemic endocrine and cardiovascular abnormalities have been previously attributed to the prevalence of obesity in these patients. A growing body of clinical evidence, however, points to a relationship between sleep apnea and its systemic abnormalities independent of obesity. We hypothesize that this association is based on a maladaptive autonomic response of chemoreceptors, reacting to the hypoxia, hypercapnia, and acidosis of sleep apnea. The elevated sympathetic response triggers an inflammatory cascade that results in a myriad of downstream consequences including insulin resistance, hypertension, diabetes, atherosclerosis and metabolic syndrome. The sympathetic bias and endocrine disturbances may further exacerbate sleep disturbance in a potentially pernicious cycle. Our proposal may extend to any chronic respiratory or metabolic conditions that manifest hypoxia, hypercapnia, and acidosis and elicit a maladaptive autonomic and inflammatory response.
Yun
A Joon
AJ
Stanford University, 300 Pasteur Drive, Palo Alto, CA 94310, USA. ayun@stanford.edu
Lee
Patrick Y
PY
Bazar
Kimberly A
KA
D000138:Acidosis / Q000473:pathology*; D001341:Autonomic Nervous System / Q000473:pathology*; D002319:Cardiovascular System / Q000473:pathology*; D004703:Endocrine System / Q000473:pathology*; D006801:Humans; D006935:Hypercapnia / Q000473:pathology*; D000860:Hypoxia; D007249:Inflammation / Q000473:pathology*; D008962:Models, Theoretical; D020181:Sleep Apnea, Obstructive / Q000473:pathology*