Effects of Acoustic Stimulation on Cardiovascular Regulation During Sleep

The interaction of wake-sleep states and acoustic stimulation on cardiovascular regulation was studied on rats implanted with electroencephalogram and electromyogram electrodes and an arterial catheter. Mild acoustic stimuli (1000 Hz, 90 dB, 50-ms beeps) were administered during Wakefulness (W), non-rapid eye movement (NREM) sleep and REM sleep and the changes induced in heart period (HP, ms) and mean arterial pressure (MAP, mmHg) were analyzed. Two 30-s sequences of beat-to-beat HP and MAP values were considered before (I) and after (II) acoustic stimulation, respectively. By the effect of stimulation, state-dependent stimulus-locked HP and MAP oscillations were observed, HP oscillations being grossly parallel to the MAP ones but delayed with respect to MAP in the ascending part only; HP and MAP spontaneous fluctuations (HP and MAP variability) increased in NREM and REM sleep (but not in W); HP vs MAP correlation coefficient increased in an algebraic sense. These results show that 1) acoustic stimulation primarily affects the peripheral resistance, and secondarily, through the baroreceptor reflex, HP, thereby increasing the impact of peripheral versus centrally driven autonomic influences on the heart; 2) in NREM sleep, heart excitability is higher than requested by the baroreflex function; 3) cardiac variability is increased by acoustic stimulation during sleep (but not in W); this, in addition to the effects of point 2, may favor cardiac arrhythmias in NREM sleep. Thus, mild acoustic stimuli not perturbing cardiovascular regulation during W may create a specific risk factor during sleep in pathophysiologic conditions

Sleep-related brain activation does not increase the permeability of the blood–brain barrier to glucose

We compared blood-brain barrier (BBB) permeability to glucose between quiet wakefulness and rapid-eye-movement (REM) sleep to assess whether changes in BBB permeability play a role in coupling glucose supply to the physiologic metabolic needs of the brain. Male Sprague-Dawley rats were prepared with electrodes for wake-sleep state scoring and with arterial and venous catheters. Using the single-pass, dual-label indicator method, unidirectional glucose extraction by the brain and cerebral blood flow (CBF) were simultaneously measured during states of quiet wakefulness ( n = 12) or REM sleep ( n = 7). The product of BBB surface area and permeability to glucose (PS product) was computed in each state. During REM sleep, CBF significantly exceeded that during quiet wakefulness in all regions but the cerebellum, whereas the difference in the PS product between quiet wakefulness and REM sleep was not statistically significant in any brain region. In the brain as a whole, CBF significantly increased 29% from quiet wakefulness to REM sleep, while a nonsignificant 0.8% increase occurred in the PS product. During REM sleep, the increase in CBF indicates a higher rate of brain glucose consumption than in quiet wakefulness, given the tight flow-metabolism coupling in the brain. Therefore, these data show that modulation of BBB permeability to glucose is not a mechanism that provides ‘energy on demand’ during the physiologic brain activation characterising REM sleep

Central and baroreflex control of heart rate during the wake-sleep cycle in rat

Spontaneous fluctuations in Heart Period (HP) and Mean Arterial Pressure (MAP) make it possible to evaluate baroreceptor-heart rate reflex sensitivity (BRS). 30-s sequences of HP and MAP beat-to-beat values were considered in the different wake-sleep states (Wake, W; Quiet Sleep, QS; Active Sleep, AS) in rats to assess whether 1) BRS changes between states and 2) the different indexes supply consistent BRS measures. BRS indexes were calculated according to validated literature procedures as regression coefficients of HP vs. MAP 1) within all ramps of increasing or decreasing MAP of four beats or more, with HP and MAP changing in the same direction (baroreflex-mediated fluctuations, BRSp), 2) within all such ramps irrespective of the relative direction of HP and MAP changes (baroreflex + non-baroreflex, i.e. non-homeostatic centrally driven, fluctuations, BRSA). HP vs. MAP regression coefficient along the entire 30-s sequence (bHPMAP) was also calculated. Results: BRSp did not change among states, BRSA decreased from QS to W to AS, bHPMAP decreased from QS to W and became negative in AS. Conclusions: 1) as indicated by BRSp, baroreflex sensitivity is state independent, 2) BRSp to BRSA to bHPMAP are increasingly affected by non-baroreflex fluctuations, BRSp being most apt to measure BRS, 3) non-homeostatic MAP and HP fluctuations increase from QS to W and prevail in AS. These potentially harmful fluctuations are normally buffered by baroreflexes: in the case of baroreflex impairment, circulatory risk may arise in conditions like AS, when they prevail

Brain capillary perfusion in the spontaneously hypertensive rat during the wake-sleep cycle

Hypertension is accompanied by circulatory changes in the brain and in other vascular districts; at disease onset, these changes may be largely functional and dependent on metabolic and vegetative drives. The wake-sleep cycle is a major physiological source of ultradian variability in autonomic function and in cerebral blood flow and metabolism. Aim of the study was to investigate whether sleep induces functional changes in the brain microcirculation in the developing hypertensive state. The fraction of brain capillaries perfused by plasma (perfused/ anatomical capillaries) was assessed in young (8-10 weeks) spontaneously hypertensive rats (SHR) during quiet wakefulness, quiet sleep and active sleep. The density of anatomical capillaries was assessed in two groups of animals using both a histochemical method (alkaline phosphatase, AP, for morphometric measurements) and an immunofluorescence method (anti-fibronectin antibodies, FN, to detect all existing capillaries). The density of perfused capillaries was determined by intravascular injection of a fluorescent marker. The fraction of anatomical capillaries perfused by plasma was always close to maximal (0.96-0.97), without significant variations among the states of the wake-sleep cycle, and was the same for AP-stained and FN-stained sections. Data thus indicate that in this model of essential hypertension no functional changes in plasma perfusion of cerebral capillaries occur in the early stages of the disease

Sleep-related brain activation does not increase the permeability of the blood-brain barrier to glucose.

We compared blood-brain barrier (BBB) permeability to glucose between quiet wakefulness and rapid-eye-movement (REM) sleep to assess whether changes in BBB permeability play a role in coupling glucose supply to the physiologic metabolic needs of the brain. Male Sprague-Dawley rats were prepared with electrodes for wake-sleep state scoring and with arterial and venous catheters. Using the single-pass, dual-label indicator method, unidirectional glucose extraction by the brain and cerebral blood flow (CBF) were simultaneously measured during states of quiet wakefulness (n=12) or REM sleep (n=7). The product of BBB surface area and permeability to glucose (PS product) was computed in each state. During REM sleep, CBF significantly exceeded that during quiet wakefulness in all regions but the cerebellum, whereas the difference in the PS product between quiet wakefulness and REM sleep was not statistically significant in any brain region. In the brain as a whole, CBF significantly increased 29% from quiet wakefulness to REM sleep, while a nonsignificant 0.8% increase occurred in the PS product. During REM sleep, the increase in CBF indicates a higher rate of brain glucose consumption than in quiet wakefulness, given the tight flow-metabolism coupling in the brain. Therefore, these data show that modulation of BBB permeability to glucose is not a mechanism that provides 'energy on demand' during the physiologic brain activation characterising REM sleep