Timing, Sleep, and Respiration in Health and Disease - Progress in Molecular Biology and Translational Science - page 192

upon the species studied and the methodologies employed. These interactions
between breathing, circadian phase, and vigilance state may have important implica-
tions for a variety of human diseases, including sleep apnea, asthma, sudden unex-
pected death in epilepsy, and sudden infant death syndrome.

1. INTRODUCTION
The physiological function most vital to mammalian existence is
breathing. Breathing provides the vital oxygen (O 2 ) that most mammalian
tissues require to function properly and expels the dangerous carbon dioxide
(CO 2 ), thus regulating serum pHwithin a tight range. This regulation main-
tains respiratory drive to ensure continued O 2 /CO 2 exchange and pH reg-
ulation. Breathing is something we, as mammals, do automatically. We can
consciously alter our breathing rate and depth, but still breathe even when
higher cortical function is isolated from the brainstem respiratory centers.
Breathing can be altered by a wide variety of factors including feedback from
airway muscles; feedback from pulmonary stretch receptors in the lungs,
body temperature, limbic factors (e.g., stress, excitement), physical exertion,
cardiac factors, and conscious modulation; and chemosensory feedback
regarding oxygen and carbon dioxide concentrations in the blood. In addi-
tion to these factors, breathing is also subject to circadian control and varies
as a function of vigilance state. Conversely, as the regulator of O 2 and CO 2
concentrations in the blood, breathing can also modify the phase and ampli-
tude of circadian rhythms and modulate vigilance state. The focus of this
review will be on the influences of circadian factors and vigilance state in
governing respiratory control, mechanisms by which respiratory control
can in turn modulate circadian rhythms and sleep-wake regulation; these
factors together can influence human disease.

2. NORMAL BREATHING
Breathing occurs automatically without the need for conscious input.
A major purpose of breathing is to allow exchange of oxygen (O 2 ) inspired
from the environment for carbon dioxide (CO 2 ) produced by the body.
This occurs at the level of the alveolar capillaries and serves to both oxygen-
ate blood for delivery to tissues and maintain arterial partial pressure of CO 2
P CO 2

ð which is the primary regulator of respiratory drive. The mammalian

respiratory tract is comprised of the nose, mouth, pharynx, larynx, trachea,

Þ