Timing, Sleep, and Respiration in Health and Disease - Progress in Molecular Biology and Translational Science - page 199

paradigm that included sleep deprivation during the study period. 99 In
another study of 10 healthy individuals, there was a trend toward circadian
variation with V E being increased during the daytime, but this failed to reach
statistical significance. While the sleep-wake cycle is subject to circadian
regulation 100,101 and sleep state can certainly affect many of these measures
as will be discussed in detail below, that these studies were performed in a
constant routine paradigm 102 suggests that circadian regulation of breathing
occurs independently of sleep state. 88,103,104
Animal studies also provide evidence for circadian regulation of breath-
ing. Using whole-body plethysmography in 21 cynomolgus monkeys
housed in a standard 12:12 light-dark cycle, Iizuka and colleagues demon-
strated circadian variation in RR, V T , and V E minute ventilation with small
reductions in RR and V T during the dark phase and larger reductions in V E
during the same time. 89 Unlike the human studies, the investigators did not
control for sleep state in this study. 89 Sprague-Dawley rats housed in a 12:12
light-dark cycle display baseline circadian variation in V CO 2 and V T / T I , but
not V T or RR. There was a trend toward increased V T in the dark, active
period, but this was not statistically significant. They did however observe a
heightened HCVR in the dark phase with CO 2 inducing larger increases in
V T and RR compared to during the light phase. In this study, only one time
point was sampled during each lighting condition. 91 Since breathing can
vary widely throughout the 24-h day and can be subject to ultradian
regulation, 105 sampling so infrequently may not be representative of the
overall pattern. Using a whole-body plethysmography method similar to
that originally described by Drorbaugh and Fenn, 106 which allows for con-
tinuous sampling of RR, V T , and V E from undisturbed behaving animals in
different environmental gas concentrations, rats were found to display a cir-
cadian variation of RR, V T , and V E . 98 Being nocturnal rodents, V E is higher
during the dark period, in contrast to the diurnal human in which V E is
higher during the light period ( Fig. 8.2 A). 98 Interestingly, while there are
circadian variations in sleep state, body temperature, activity, and metabo-
lism and all of these certainly affect V E , observed circadian variations in V E
seem to occur independently of these factors. 87,107
In addition to circadian variation in RR and V E , there is circadian var-
iation in airway tone and sensitivity to respiratory stimuli. There are diurnal
variations in FEV 1 , 108 PEF, 109,110 and specific airway conductance. 111 All of
these changes are a direct function of airway tone. In the same study of
10 healthy male participants mentioned above, Spengler and Shea observed
circadian variation in FEV 1 and FEV 1 /FVC, but not in FVC or PEF. In this