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

UNLABELLED: 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 BRS(A) 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 during sleep.

Brain capillary perfusion was evaluated in the different states of the wake-sleep cycle-quiet wakefulness (QW), quiet sleep (QS), and active sleep (AS)-in rats. The extent of the perfused capillary network was determined by intravascular distribution of a fluorescent marker. Evans blue (EB); it remained unchanged across the three behavioral conditions, QW, QS, and AS. The anatomical network was assessed by alkaline phosphatase (AP) endothelial staining, which is known to underestimate the number of existing capillaries. The resulting number of AP profiles were, therefore, significantly lower than the number of EB profiles, but the percentage of AP-stained capillaries that were perfused (96%) was also unchanged across the behavioral conditions. The results indicate that no capillary recruitment accompanies the wake-sleep cycle. Capillary surface area is a relevant factor in determining exchanges across the blood-brain barrier. In the absence of capillary recruitment (relative constancy of the surface area), the CBF changes during sleep should preferentially affect flow-limited with respect to diffusion-limited transport.

Brain blood flow and extracerebral carotid circulation during sleep in rat.

Cerebral blood flow (CBF) and blood flow (BF) in extracerebral head structures were measured during the sleep-wake cycle in rats using radioactive microspheres. While no statistically significant changes occurred in the transition from Waking to quiet sleep (also referred to as synchronized or non-REM Sleep), CBF increased significantly in active sleep (AS, also referred to as desynchronized or REM Sleep) in all structures considered, with the sole exception of the cerebellum. In extracerebral head structures, no significant state-dependent BF changes were found. Factor Analysis however extracted a common factor accounting for BF variability in the external carotid circulation. This factor was uncorrelated with CBF changes in AS, suggesting independent regulation of the two vascular beds in this sleep state.

Spinal cord blood flow changes during the sleep-wake cycle in rat.

Regional spinal cord blood flow was measured in rats during the sleep-wake cycle with the use of radioactive microspheres. Spinal cord blood flow decreases from wakefulness to quiet (synchronized) sleep while increasing in active (desynchronized) sleep. Blood-flow changes depend on changes in vascular resistance whose mechanisms have yet to be elucidated. Blood-gas tension or mean arterial pressure, however, do not play a relevant causal role.

Shivering during sleep: relationship between muscle blood flow and fiber type composition.

The present study considers in rabbit: i) the relationship between muscle blood flow (BF) increase and fiber-type composition during shivering; ii) the influence of the vigilance states (Quiet Wakefulness, QW; Synchronized Sleep, SS; Desynchronized Sleep, DS) on this relationship. The results show that muscle BF increase during shivering is proportional to the slow-twitch oxidative (SO) fiber component in QW and SS; in DS the proportionality is lost. This is in accordance with the disappearance of shivering, together with all thermoregulatory effector responses, in this sleep state. Another muscle circulation pattern occurring at low ambient temperature, the relationship between BF increase and muscle depth, also disappears in DS. This confirms that the integrative control of muscle circulation, like other integrative mechanisms, is impaired during DS.

Loss of integrative control of peripheral circulation during desynchronized sleep.

Regional blood flow (BF) changes during sleep were measured in rabbits at low, neutral, and high ambient temperatures (Ta) with radioactive microspheres. At both low and high Ta, peripheral vasomotor changes at the onset of desynchronized sleep (DS) were incompatible with thermoregulatory homeostasis. At low Ta, BF decreased in muscle (with the disappearance of shivering), whereas it increased in the arteriovenous anastomoses (AVA) and in the splanchnic bed. At high Ta, BF decreased in muscle (with the disappearance of panting) and in the AVA, whereas it increased in the splanchnic bed. An impaired central nervous regulation underlies the disruption of peripheral circulation patterns in this sleep stage. The lack of adaptive vasomotor adjustments in DS, which has little consequence in normal conditions, may become relevant in cardiovascular pathophysiology when BF redistribution through increased neurogenic vasomotor activity becomes a major compensating mechanism.

Regional splanchnic blood flow during sleep in the rabbit.

Regional splanchnic blood flow (rSBF) was measured in rabbits with the radioactive microsphere technique. No statistically significant changes occurred in rSBF or vascular conductances in relation to the different states of the sleep-waking cycle (quiet-wakefulness, synchronized sleep, and desynchronized sleep).

Muscle blood flow changes during sleep as a function of fibre type composition.

In rabbits blood flow was measured in 19 muscles with the radioactive microsphere technique. Fibre type composition (SO, slow-twitch oxidative; FOG, fast-twitch oxidative-glycolytic; FG, fast-twitch glycolytic) was determined histochemically for the same muscles. While no significant changes occur in the transition from quiet wakefulness (QW) to synchronized sleep (SS), in desynchronized sleep (DS) blood flow decreases in SO and increases in FOG and FG fibres. These changes may be related to the changes in motor activity characteristic of DS: muscle atonia and twitches, respectively.

Brain circulation during sleep and its relation to extracerebral hemodynamics.

Regional cerebral blood flow (rCBF) was measured in rabbits during the sleep-waking cycle, using radioactive microspheres. rCBF does not change significantly in the transition from wakefulness (W) to synchronized sleep (SS), while it significantly increases during desynchronized sleep (DS). No correlation was found between CBF changes and changes in cardiac output or regional blood flows in the transition from SS to DS. This suggests that the CBF increase in DS is not relevantly affected by changes in extracerebral hemodynamic factors.

Regional spinal cord blood flow during sleep-waking cycle in rabbit.

Spinal cord blood flow (SCBF) was measured in rabbits during the sleep-waking cycle with the use of radioactive microspheres. The values obtained during wakefulness (W), synchronized sleep (SS), and desynchronized sleep (DS) were 18.1 +/- 2.1, 18.9 +/- 2.6, and 34.4 +/- 2.5 (SE) ml X min-1 X 100 g-1, respectively. Differences relative to SS were not significant in W and were significant at the 0.05 level in DS (modified t test and Bonferroni's method). The increase in blood flow during DS was due to a decrease in vascular resistance. The mechanism of the vasodilation during DS has yet to be identified.

Influence of brown adipose tissue on deep cervical temperature during sleep in the young rabbit.

In young rabbits the slope of the temperature in the deep cervical region close to brown adipose tissue increased during desynchronized sleep at low ambient temperature. No increase occurred at neutral ambient temperature. In control rabbits (after disappearance of brown adipose tissue), the slope of deep cervical temperature did not increase during desynchronized sleep at low or neutral ambient temperatures.

Neural control of vasomotion in rabbit ear is impaired during desynchronized sleep.

In a warm environment the skin vessels of the rabbit ear, dilated during synchronized sleep (SS), reduce their caliber during desynchronized sleep (DS). In a cold environment the ear skin vessels, constricted during SS, increase their caliber during DS. These vascular changes contrast with thermoregulatory homeostasis. They can be accounted for by the decrease in both local transmural pressure and sympathetic vasoconstrictor discharge accompanying the DS phase. A decrease in local transmural pressure prevails in a warm environment and a decrease in sympathetic discharge in a cold environment. Accordingly, the vessel caliber decreases in the heat and increases in the cold. The results of the sympathetic denervation of the ear and of the alpha-receptor blockade confirm the passive nature of vascular changes in the rabbit ear during DS.

Short-term thermoregulatory adjustments to ambient temperature changes in the rabbit. I. Theoretical model.

A model of thermoregulation is proposed, based on additive features found both in the processing of thermal information and in the interaction between thermoregulation and other vegetative functions. According to this model, it may be expected that, if temperature changes are induced in some thermal inputs, other thermal inputs will show specular temperature changes. The model has been experimentally tested.

Short-term thermoregulatory adjustments to ambient temperature changes in the rabbit. II. Experimental results.

Rabbits housed at constant ambient temperature (Ta = 22 +/- 1 degree C) were exposed, in different sessions, to different Ta's, ranging from 0 to 25 degrees C. The steady values of both ear skin (Ts) and hypothalamic (Thy) temperature were measured. Ts appeared to be positively correlated with Ta, while, on the contrary, Thy was found to be negatively correlated with Ta. specular changes, therefore, were induced on Ts and Thy by Ta changes, according to the additive model proposed in a previous paper.

[Depression of responsivity of the preoptic region to repetitive electric stimulation during desynchronized sleep]. / Depressione della responsività della regione preottica alla stimolazione elettrica iterativa durante il sonno desincronizzato.

Respiratory effects of preoptic and vagal repetitive electrical stimulation were studied in unrestrained cats during sleep. Preoptic stimulation influenced breathing during synchronized sleep, but not during desynchronized sleep. Breathing was affected by vagal stimulation during both synchronized and desynchronized sleep, although an increase in threshold was apparent during the latter stage of sleep. The results show that the depression of preoptic responsiveness during desynchronized sleep is non-specific.

Respiratory effects of preoptic-anterior hypothalamic electrical stimulation during sleep in cats.

The respiratory effects of preoptic-anterior hypothalamic (PO-AH) and vagal repetitive electrical stimulation (RES) were studied in unrestrained cats during sleep. PO-AH RES influenced breathing consistently during synchronized sleep but only occasionally during desynchronized sleep. Induction of desynchronized sleep by PO-AH RES was also observed. The respiratory effects of PO-AH RES on one side were enhanced by concomitant PO-AH warming on the other side during synchronized sleep but not during desynchronized sleep. Breathing was affected by vagal RES during both sleep stages, although an increase in threshold and in variability of respiratory responses was apparent during the latter sleep stage. The results show that PO-AH unresponsiveness during desynchronized sleep is nonspecific.

Interactions between temperature regulation and emotional arousal in the rabbit.

In our study we examined, in the rabbit, the interactions between temperature regulation and the state of increased vigilance and emotional arousal induced by a Classical Aversive Conditioning Procedure. A Delay Conditioning Procedure was used. The Conditioned Stimulus (CS) was a 1350 Hz, 85 dB tone, the Unconditioned Stimulus (UCS) a 1 mA, 0.5 s shock. Testing sessions were run at different ambient temperatures from 5 to 30 degrees C. At all ambient temperatures considered the CS induced desynchronisation of the EEG and stereotyped changes in all the autonomic variables studied. Hypothalamic temperature (Thy) first increased, then decreased below its initial value, whereas ear skin temperature (Ts) showed opposite changes. Respiratory frequency (RF) initially increased, then tended to revert to its original value. The average time course of this complex pattern was 300 s from the CS. The overall effect of the CS sequence in a session was a significant decrease in Thy and Ts and a significant increase in RF compared to control values at the beginning of the session. Both in the short (single trial) and long terms (whole session) the autonomic responses induced by the emotional stress (polypnoea and vasoconstriction) were not coherent from the point of view of thermoregulation. The hypothesis of an effect of emotional arousal in shifting set point temperatures can therefore be discarded in favour of a direct action of emotional stress on effector controllers for respiration and vasomotion.

Quantitative analysis of short term deprivation and recovery of desynchronized sleep in cats.

A quantitative analysis of desynchronized sleep (DS) deprivation (exposure to low ambient temperature) and recovery was carried out in unrestrained cats. The results show that: (1) the circadian obligate quota of DS is precisely regulated by a control mechanism paying by the 24th h the DS debt induced by up to 14 h of total DS deprivation, if recovery occurs during the rest phase of circadian photoperiodicity (CP); (2) during static rebound DS hourly duration is increased by 40 +/- 4 sec/h of total deprivation (mean and S.E.) and there is a statistically significant increase in the hourly frequency and in the duration of DS episodes, with respect to control values; (3) the hourly obligate and facultative quotas of DS amount to 409 +/- 82 and 229 +/- 140 sec/h (mean and S.D.), respectively. (4) preoptic heating during deprivation at low ambient temperature decreases the DS static rebound during recovery at control ambient temperature by an amount corresponding to the cumulative duration of DS episodes elicited by the preoptic treatment; (5) preoptic temperature decreases the more markedly the shorter the duration of exposure to low ambient temperature and regains control values the sooner the smaller the DS debt incurred during deprivation; (6) DS debt cumulation is a continuous process which develops at a steady rate during day and night, whereas DS debt payment is a discontinuous process (ultradian rhythm of DS) which develops at a variable rate depending on the DS debt and on the phase of CP.