Sleep/wakefulness versus urethane anesthesia: analogous arousal states for respiratory control?

• Main Author: Hunter, Julia D.
• Language: English
• Published: 2008
• Online Access: http://hdl.handle.net/2429/2566

Under light urethane anesthesia, animals cycle through patterns of EEG activity which superficially appear like waking (W), light sleep (LS) and slow-wave sleep (SWS) in the unanesthetized animal, referred to as States I, II and DI, respectively. The major question in this thesis was whether the urethane anesthetic states are analogous to the natural states with similar EEG patterns, at least in terms of respiratory and cardiovascular function. Therefore, the first objective of this study was to examine the effects of sleep state on respiratory and cardiovascular variables, and to compare these effects to those observed during superficially similar arousal states in urethane-anesthetized animals. In order to further determine whether the arousal states observed during urethane anesthesia were analogous to sleep/wake states in terms of respiratory and cardiovascular control, the effects of sleep state on hypoxic and hypercapnic ventilator responses were assessed and compared to the effects of arousal states with similar EEG patterns on these responses in urethane-anesthetized animals. Electroencephalographic (EEG), electromyographic (EMG) and electrocardiographic (EKG) activity were monitored during the different arousal states in sleeping and anesthetized animals under normoxic, hypoxic and hypercapnic conditions. Respiratory variables were also measured under these conditions using whole-body plethysmography in unanesthetized animals, and using a face mask and pneumotachograph in the anesthetized animals. Golden-mantled ground squirrels spent approximately 33% of the time in wakefulness(W), 31% to 14% in light sleep (LS) and 32% to 48% in slow-wave sleep (SWS). Less than 5%of the time was spent in rapid-eye-movement (REM) sleep. Urethane-anesthetized animals spent approximately the same amount of time in each arousal state (States I, 11 and III), and these proportions were the same as those observed in unanesthetized animals in states with similar cortical patterns. Hypoxic (10.0% 02) and hypercapnic (5.0% CO2) conditions reduced the amount of synchronized activity and produced greater amounts of desynchronized activity, but in different ways. These effects, however, were the same in both unanesthetized and urethane-anesthetized animals. In both groups, hypoxic exposure resulted in more LS/State II, while the amount of time spent in W/State I was unaltered, but hypercapnic exposure produced greater amounts of W/State I, while the amount of time spent in LS/State H was unaltered. In all three parts of the present study, sleep states exerted a strong, negative influence on breathing frequency, but had less consistent effects on tidal volume. In general, the net effect was that sleep reduced minute ventilation, although in one part of the study, this decrease was a nonsignificant trend only. These effects of sleep were similar in SWS and REM sleep. Theurethane-anesthetized animals demonstrated exactly the same alterations in respiratory variables in arousal states exhibiting similar EEG patterns. Unlike many previous reports in other species, the present study revealed that golden-mantled ground squirrels increase their ventilatory sensitivity to hypoxia and hypercapnia during sleep. The urethane-anesthetized animals also showed these same increases in ventilator sensitivity to hypoxia and hypercapnia as they moved into arousal states with synchronized cortical activity (State III). Like respiration, heart rate was also affected by sleep/wake states in the golden-mantled ground squirrel. As animals moved into deeper sleep states (ie. SWS from W and LS), heart rate decreased. Additionally, more variability in the heart rate was observed during sleep, due to a greater preponderance of respiratory sinus arrhythmia. The sinus arrhythmia was most evident during REM sleep. Urethane anesthesia increased heart rate well above the levels observed in the unanesthetized animals; this increase was due in part to the abolishment of respiratory sinus arrhythmias. However, in spite of this increase, heart rate still decreased in arousal states with synchronized EEG patterns in the urethane-anesthetized animals, Thus, the increase in heart rate appeared to be a tonic effect of the anesthesia, but although superimposed on this background increase, the effect of arousal state was still evident. In conclusion, the changing cortical patterns observed under light urethane anesthesia mimic sleep/wake states with respect to natural oscillations between arousal states, their influence on respiratory and cardiovascular control under normoxic, hypoxic and hypercapnic conditions, as well as the changes in state induced by hypoxic and hypercapnic exposure. These observations support the hypothesis that, in terms of cardio-respiratory function, the various states seen under urethane anesthesia with EEG activity similar to wakefulness, light sleep and slow-wave sleep, are analogous states.