Fetal breathing, sleep state, and cardiovascular responses to graded anemia in sheep

Graded anemia was produced for 2 h in 10 unanesthetized fetal sheep by infusing plasma in exchange for fetal blood. This reduced the mean fetal hematocrits during the 1st h of anemia to 19.7 +/- 0.5% [control (C) = 28.2 +/- 1.1%] for mild anemia, 17.4 +/- 0.9% (C = 30.0 +/- 1.1%) for moderate anemia, and 15.1 +/- 1.0% (C = 29.2 +/- 1.3%) for severe anemia. The respective mean arterial O2 contents (CaO2) were 4.46 +/- 0.20, 3.89 +/- 0.24, and 3.22 +/- 0.19 ml/dl. Mean arterial PO2 was reduced significantly (by 2 Torr) only during moderate anemia, and mean arterial pH was decreased only during severe anemia. No significant changes occurred in arterial PCO2. Fetal tachycardia occurred during anemia. Mean arterial pressure was reduced by 2-3 mmHg during mild anemia; however, no significant blood pressure changes were observed for moderate or severe anemia. The incidence of rapid-eye movements and breathing activity was not affected by mild anemia, but the incidence of both was reduced significantly during moderate and severe anemia. It is concluded that 1) a reduction in CaO2 of greater than 2.48 +/- 0.22 ml/dl by hemodilution inhibits rapid-eye movements and breathing activity, and 2) the PO2 signal for inhibition does not come from arterial blood but from lower PO2 in tissue.     

Fetal breathing, sleep state, and cardiovascular responses to graded hypoxia in sheep

We studied changes in glycosaminoglycan content and concentration during postresectional compensatory lung growth in adult male rats. After right trilobectomy, left lung dry weight was normal at 4 days, increased 74% between 4 and 7 days, and more slowly over the next week. Total glycosaminoglycan content per milligram dry lung weight increased early and rapidly, reaching 189% of the control value at 4 days postresection. The magnitude and temporal pattern of increase was different for different glycosaminoglycan subtypes. Hyaluronate and chondroitin sulfate content were increased by 198 and 113%, respectively, at 4 days, with no further increases subsequently. Heparan sulfate content increased more slowly and steadily, and dermatan sulfate concentrations did not change. At 4 days, the percent of total glycosaminoglycans that was hyaluronate was almost doubled, whereas the percent that was heparan sulfate was decreased; by day 7 the percent compositions had returned to normal. We conclude that changes in glycosaminoglycans occur early in postresectional lung growth and speculate that they may play a facilitatory role.     

Fetal breathing and sleep state responses to graded carboxyhemoglobinemia in sheep

To investigate CO effects on brain oxygenation, graded carboxyhemoglobinemia (HbCO) was produced in nine unanesthetized fetal sheep by infusing CO-laden erythrocytes in exchange for fetal blood. For the 1st h after this procedure, the mean fetal carboxyhemoglobin levels were 16.5 +/- 0.4% [control (C) = 1.4 +/- 0.4%] for mild HbCO, 22.7 +/- 0.6% (C = 1.8 +/- 0.4%) for moderate HbCO, and 27.8 +/- 0.5% (C = 2.1 +/- 0.7%) for severe HbCO. This induction of HbCO significantly reduced mean preductal arterial PO2 values to 4.3 Torr below control for mild HbCO, 4.6 Torr below control for moderate HbCO, and 5.5 Torr below control for severe HbCO. The respective arterial O2 contents were decreased by 17, 21, and 29%. Mean arterial pH was lowered only during severe HbCO, and arterial PCO2 values were unchanged. HbCO produced a fetal tachycardia. Mean arterial blood pressure was only increased during severe HbCO. The incidences of rapid eye movements and breathing activity were decreased by HbCO in a dose-dependent manner. When related to calculated brain tissue PO2, these decreases were similar to those measured during hypoxic hypoxia and anemia, suggesting that carboxyhemoglobin effects result solely from diminished oxygenation. It is concluded that 1) the peripheral arterial chemoreceptors in the fetus apparently have little effect on hypoxic inhibition of breathing and 2) the carboxyhemoglobin concentrations required to inhibit fetal breathing are greater than those likely to be encountered clinically.     

Fetal breathing and cardiovascular responses to graded methemoglobinemia in sheep

Graded methemoglobinemia (MetHb) was produced in unanesthetized fetal sheep to determine the effects on brain oxygenation. MetHb was induced by infusing methemoglobin-containing erythrocytes in exchange for fetal blood. During the hour after MetHb was established, fetal methemoglobin concentrations averaged 1.23 +/- 0.12 (mild MetHb), 1.71 +/- 0.13 (moderate MetHb), and 2.27 +/- 0.17 g/dl (severe MetHb). MetHb reduced mean arterial O2 content by approximately 19 (mild MetHb), 29 (moderate MetHb), and 39% (severe MetHb). The average preductal arterial PO2 fell by 1.6 (-7%), 2.8 (-11%), and 4.0 Torr (-16%) for mild, moderate, and severe MetHb, respectively. Fetal heart rate increased significantly during mild and moderate MetHb, and mean arterial pressure fell slightly during moderate and severe MetHb. The incidences of fetal breathing and eye movements were reduced in a dose-dependent manner when the calculated brain end-capillary PO2 was less than 14 Torr. We conclude that: 1) the effective capillary PO2 in the fetal brain can be significantly reduced by increasing the distance between non-methemoglobin-laden erythrocytes in capillaries and 2) hypoxic inhibition of fetal breathing probably arises from discrete areas of the brain having a PO2 less than 3 Torr.     

Plasma adenosine and cardiovascular responses to dipyridamole in fetal sheep.

The effects of dipyridamole infusion on fetal arterial plasma adenosine level, [ADO], and the systemic cardiovascular system were studied in 10 fetal sheep at 130-135 days gestational age. Dipyridamole (0.25 mg/kg) was infused into the fetuses intravenously during normoxia and hypoxia. Plasma [ADO] was measured using high-performance liquid chromatography, (HPLC), and fetal heart rate and arterial blood pressure were monitored throughout the study. These studies were performed in the absence and presence of theophylline, an adenosine receptor antagonist. During normoxia (PO2, 23.8 +/- 2.0 Torr), dipyridamole infusion increased fetal plasma [ADO] from 0.82 +/- 0.10 microM to 1.41 +/- 0.16 microM within 1 min (P < 0.01) and fetal heart rate from 157 +/- 6 bpm to 174 +/- 7 bpm (P < 0.01), but did not change mean blood pressure. Fetal plasma [ADO] and fetal heart rate returned to basal levels quickly. Treatment with theophylline did not alter the elevation of plasma [ADO] after dipyridamole infusion, but abolished responses of fetal heart rate to dipyridamole infusion. After 15 min of hypoxia with an average arterial PO2 of 15.4 +/- 1.1 Torr, fetal plasma [ADO] increased to 1.15 +/- 0.14 microM (P < 0.01). Dipyridamole infusion then further raised fetal plasma [ADO] to 1.67 +/- 0.27 microM (P < 0.01). The duration of the increase of fetal plasma [ADO] after dipyridamole infusion was no longer in hypoxia than in normoxia, however there was no significant change in the pattern of transient fetal bradycardia and persistent hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of plasma adenosine in breathing responses to hypoxia in fetal sheep.

The importance of plasma adenosine in hypoxic inhibition of breathing movements was determined in chronically catheterized fetal sheep (greater than 0.8 term). Preductal arterial blood for adenosine measurements was withdrawn using a double lumen catheter to mix blood entering the catheter with a solution to stop adenosine metabolism. In 6 fetuses, isocapnic hypoxia (delta PaO2 congruent to -10 Torr) increased the average plasma adenosine concentration from 1.1 +/- 0.2 (SEM) to 2.0 to +/- 0.4 microM. During hypoxia, plasma levels of adenosine were inversely related to preductal arterial O2 content (CaO2) with values ranging between 1.6 and 4.0 microM when CaO2 was less than 3 ml/dl. Hypoxia also significantly reduced the incidence of fetal breathing and rapid eye movements. In other experiments, adenosine (0.36 +/- 0.03 mg/min/kg) was infused for one hour into the inferior vena cava of 5 fetuses. During this infusion, mean plasma concentration of adenosine was 2.8 +/- 0.3 microM, a value about 2.5 times the control average. Adenosine also significantly reduced the incidence of low voltage electrocortical activity, rapid eye movements and breathing activity. We conclude that hypoxic inhibition of fetal breathing most likely arises from an increase in central adenosine production, although during severe O2 deprivation (CaO2 less than 3 ml/dl) blood-borne adenosine could also contribute.     

Fetal breathing adaptation to prolonged hypoxaemia in sheep

Prolonged (6 days) fetal hypoxaemia was produced by placing pregnant ewes in an environmental chamber. A constant flow of N2 into the chamber reduced the fraction of inspired oxygen (Fi02) to 0.139 +/- 0.001, simulating an altitude of 4270 m. This reduced maternal PaO2 by about 39 mmHg and PaCO2 by nearly 5 mmHg, which produced a hypocapnic (delta PaCO2 = -5 mmHg) hypoxaemia (delta PaO2 = -8 mmHg) in the fetus. An analysis of the first 4 h of breathing recorded each day (1800-2200 h; start of hypoxaemia: 1200 h) showed that the incidence (12 +/- 2.0 min/day) during the first day of hypoxaemia was significantly less (P less than 0.05) than that (24 +/- 3.1 min/h) during the same time of the control day. By the second day, breathing had returned to normal. Further analysis indicated that a normal incidence of breathing may have occurred as early as 14 h after starting hypoxaemia. These results suggest that fetal breathing movements adapt rather quickly to this degree of hypocapnic hypoxaemia.     

Effects of hypoxaemia and hypercapnia on breathing movements and sleep state in sinoaortic-denervated fetal sheep

The role of the systemic arterial chemoreceptors in regulating breathing movements was determined in 7 chronically catheterized fetal sheep with carotid denervation and vagal section. Fetal hypoxaemia (delta PaO2 = -11.4 +/- 0.6 mmHg) decreased significantly the incidence of rapid-eye-movements (control = 26 +/- 1.5 min/h; hypoxia = 12 +/- 2.6 min/h, P less than 0.001) and breathing activity (control = 18 +/- 1.0 min/h; hypoxia = 8 +/- 1.1 min/h, P less than 0.001). However, the lag in onset of inhibition (approximately 8 min) was significantly greater (P less than 0.05) than for normal fetuses. The incidence of low voltage electrocortical activity was not affected. Hypercapnia (delta PaCO2 = 9.5 +/- 1.1 mmHg) increased significantly the incidence of rapid-eye-movements and breathing activity. Hypercapnia also increased the mean amplitude of breathing activity and reduced the average breath interval. Rapid-eye-movements and breathing activity were depressed significantly by hypoxaemic hypercapnia. These observations suggest that hypoxic inhibition does not require afferent activity from the aortic or carotid bodies nor from other chemoreflexes mediated by the vagus. However, such peripheral input may be responsible for a more rapid onset of inhibition in normal fetuses.     

Fetal responses to maternal and intra-amniotic lipopolysaccharide administration in sheep

A link between intrauterine infection and premature labor is widely accepted, yet the fetal inflammatory responses to such infections are not well understood. Our aim was to use a sheep model in which an inflammatory state was induced by lipopolysaccharide (LPS) administration during pregnancy to the maternal systemic, intra-amniotic or extra-amniotic compartments. Fetal and maternal blood gases and uterine electromyographic activity along with fetal and maternal circulating concentrations of prostaglandins PGE2 and PGFM, cortisol, and interleukin-6 were determined. Maternal systemic LPS treatment resulted in mild maternal hypoxemia, a rise in temperature, greater fetal hypoxemia, and a marked rise in fetal cortisol and PGE2 concentrations that persisted for 48 h. Intra-amniotic administration of LPS at doses higher than those used systemically caused an increase in fetal cortisol and PGE2 concentrations as well as a rise in uterine activity, but these were lesser in magnitude. Extra-amniotic LPS administration caused no overt fetal or maternal inflammatory responses. We conclude that maternal LPS treatment markedly elevated fetal cortisol and PGE2 concentrations. This may be a potential protective mechanism that aids the fetus in the event of premature delivery. The attenuated fetal response to intra-amniotic LPS treatment, despite the much higher dose used, may support a role for the amniotic fluid in protecting the fetus from endotoxin exposure during pregnancy.     

Drug-induced changes in fetal breathing activity and sleep state

Drugs reported to stimulate fetal breathing (FB) were injected into a femoral vein of near-term fetal lambs during rapid eye movement (REM) and non-REM (NREM) sleep. The primary response to NaCN, 0.25-0.5 mg, a dose which did not flatten the electrocorticogram, was a brief burst of gasping in any sleep state. When injected during REM sleep, NaCN caused the cessation of spontaneous FB and the onset of gasping. Stimulation of FB was observed infrequently. Caffeine (10 mg) and doxapram (3 mg) frequently caused an immediate change in sleep state or arousal. The incidence of FB increased concomitantly with a change to REM sleep or wakefulness (W), but FB still ceased with the onset of NREM sleep. When administered during an episode of spontaneous FB during REM sleep, both caffeine and doxapram caused stimulation of the frequency and depth of breathing. Pilocarpine (4 mg) caused arousal and gasping followed by prolonged vigorous breathing that was dependent on intact carotid sinus nerves. Indomethacin (120 mg over several hours) did not affect sleep states but induced FB in both NREM and REM sleep. In summary, in the fetus the primary effect of NaCN is to suppress spontaneous FB and induce gasping and the effects of pilocarpine, caffeine, and doxapram are intimately related to sleep states or arousal. Indomethacin causes the conversion from episodic fetal to continuous postnatal-type breathing. These data indicate the importance of assessing fetal state of consciousness in interpreting the respiratory response to drugs.     

Fetal breathing and behavior measured through a double-wall Plexiglas window in sheep

The inability to see the fetus makes the assessment of fetal behavior difficult. To circumvent this problem we implanted a Plexiglas window in the left flank of the ewe. Fetuses were instrumented for measurements of sleep, breathing, and swallowing. Ten fetal sheep were studied on 32 occasions. Six fetuses were delivered through the window at term, and postnatal behavior was compared with intrauterine behavior. Fetuses observed during resting conditions alternated between periods of quiet sleep [high-voltage electrocortical activity (ECoG)] and active or rapid-eye-movement sleep (low-voltage ECoG). In quiet sleep, movements were absent except for periodic generalized electromyographic discharges. Eye and breathing movements were rare or absent. Swallowing was also absent. In active sleep, movements were increased with powerful breathing and swallowing activity. Fetal wakefulness defined by open eyes and purposeful movements of the head was never seen in utero but was clearly observed after delivery. We conclude that fetal wakefulness as defined postnatally was not able to be demonstrated in utero.     

Effect of positive-pressure breathing on cardiovascular and thermoregulatory responses to exercise

Five healthy male volunteers performed 20 min of both seated and supine cycle-ergometer exercise (intensity, 50% maximal O2 uptake) in a warm environment (Tdb = 30 degrees C, relative humidity = 40-50%) with and without breathing 10 cmH2O of continuous positive airway pressure (CPAP). The final esophageal temperature (Tes) at the end of 20 min of seated exercise was significantly higher during CPAP (mean difference = 0.18 +/- 0.04 degree C, P less than 0.05) compared with control breathing (C). The Tes threshold for forearm vasodilation was significantly higher (P less than 0.05) during seated CPAP exercise than C (C = 37.16 +/- 0.13 degrees C, CPAP = 37.38 + 0.12 degree C). The highest forearm blood flow (FBF) at the end of exercise was significantly lower (P less than 0.05) during seated exercise with CPAP (mean +/- SE % difference from C = -30.8 +/- 5.8%). During supine exercise, there were no significant differences in the Tes threshold, highest FBF, or final Tes with CPAP compared with C. The added strain on the cardiovascular system produced by CPAP during seated exercise in the heat interacts with body thermoregulation as evidenced by elevated vasodilation thresholds, reduced peak FBF, and slightly higher final esophageal temperatures.     

Systemic and pulmonary hemodynamic responses to normal and obstructed breathing during sleep

Schneider, H., C. D. Schaub, K. A. Andreoni, A. R. Schwartz,R. L. Smith, J. L. Robotham, and C. P. O'Donnell. Systemic andpulmonary hemodynamic responses to normal and obstructed breathing during sleep. J. Appl. Physiol. 83(5):1671-1680, 1997.We examined the hemodynamic responses to normalbreathing and induced upper airway obstructions during sleep in acanine model of obstructive sleep apnea. During normal breathing,cardiac output decreased (12.9 ± 3.5%,P < 0.025) from wakefulness tonon-rapid-eye-movement sleep (NREM) but did not change from NREM torapid-eye-movement (REM) sleep. There was a decrease(P < 0.05) in systemic (7.2 ± 2.1 mmHg) and pulmonary (2.0 ± 0.6 mmHg) arterial pressures fromwakefulness to NREM sleep. In contrast, systemic (8.1 ± 1.0 mmHg,P < 0.025), but not pulmonary,arterial pressures decreased from NREM to REM sleep. During repetitiveairway obstructions (56.0 ± 4.7 events/h) in NREM sleep, cardiacoutput (17.9 ± 3.1%) and heart rate (16.2 ± 2.5%) increased(P < 0.05), without a change instroke volume, compared with normal breathing during NREM sleep. Duringsingle obstructive events, left (7.8 ± 3.0%,P < 0.05) and right (7.1 ± 0.7%, P < 0.01)ventricular outputs decreased during the apneic period. However, left(20.7 ± 1.6%, P < 0.01) andright (24.0 ± 4.2%, P < 0.05)ventricular outputs increased in the postapneic period because of anincrease in heart rate. Thus 1) thesystemic, but not the pulmonary, circulation vasodilates during REMsleep with normal breathing; 2)heart rate, rather than stroke volume, is the dominant factormodulating ventricular output in response to apnea; and3) left and right ventricular outputs oscillate markedly and in phase throughout the apnea cycle.

     

Thalamic lesions dissociate breathing inhibition by hypoxia and adenosine in fetal sheep

The effects of diencephalic lesions on respiratory responses to intra-arterially infused adenosine (ADO) were determined in chronically catheterized fetal sheep (>0.8 term). These studies were designed to test the hypothesis that the inhibitory effects of ADO on fetal breathing, like those of hypoxia, are mediated by the parafascicular nuclear complex (Pf) of the posteromedial thalamus. ADO inhibited breathing [control (C): 26 +/- 2.6, ADO: 4 +/- 1 min/h] in normal fetuses and in a fetus with a lesion that virtually destroyed the thalamus but left intact most of Pf. Neuronal lesions in the diencephalon, produced by injecting ibotenic acid, abolished the inhibitory effects of ADO on breathing (C: 31 +/- 5.1, ADO: 30 +/- 4.5 min/h) when the lesions encompassed Pf or the sector immediately rostral to Pf that retained the capacity to regulate hypoxic inhibition. Smaller lesions created by the insertion of needles also eliminated the depressant effects of ADO when disruptions were within Pf or a rostral component of the thalamic cortical activating system. It is concluded that 1) a medial thalamic sector is critically involved in ADO-induced apnea and 2) ADO-dependent and ADO-independent mechanisms mediate hypoxic inhibition.     

Fetal cardiovascular responses to asphyxia induced by decreased uterine perfusion

Cardio-respiratory responses to asphyxia produced by decreased uterine perfusion were studied in 15 sheep fetuses. In chronic (spinal-anesthetized) and acute (inhalation-anesthetized) preparations, we measured fetal PO2, PCO2, pH, heart rate, arterial and umbilical venous pressures at rest and 5 min after controlled reductions of maternal aortic blood flow. Umbilical blood flow was determined by electromagnetic flow transducer on the fetal descending aorta with the iliac arteries ligated, in conjunction with radionuclide-labelled microspheres. In contrast to previous studies in which fetal hypoxaemia was produced by decreased maternally inspired O2 concentrations, decreasing degrees of uterine perfusion were associated with increasing degrees of hypercapnea and acidemia, as well as hypoxaemia. In chronic experiments, heart rate and umbilical blood flow fell significantly in response to decreased uterine perfusion with all degrees of hypoxaemia studied. In acute experiments, during the control period, PO2 values were similar to those of chronic experiments while values for pH and umbilical blood flow were lower and those for umbilical vascular resistance were higher. In the acute experiments, hypoxic stresses identical to those in the chronic studies failed to produce significant hemodynamic changes, except for bradycardia in response to severe hypoxaemia. These differences were apparently due to the pharmacologic effects of halothane and the operative stresses.     

Fetal breathing and pressures in the trachea and amniotic sac during oligohydramnios in sheep

Oligohydramnios commonly leads to fetal lung hypoplasia, but the mechanisms are not fully understood. Our aim was to determine, in fetal sheep, the effects of prolonged oligohydramnios on the incidence and amplitude of tracheal pressure fluctuations associated with fetal breathing movements (FBM), on tracheal flow rate during periods of FBM (VtrFBM) and periods of apnea (Vtrapnea), on tracheal pressure relative to amniotic sac pressure, and on amniotic sac pressure relative to atmospheric pressure. In five sheep, oligohydramnios was induced by draining amniotic and allantoic fluids from 107 to 135 days of gestation (411.8 +/- 24.4 ml/day), resulting in fetal lung hypoplasia. In five control sheep, amniotic fluid volume was 732.3 +/- 94.4 ml. Oligohydramnios increased the incidence of FBM by 14% at 120 and 125 days and the amplitude of FBM by 30-34% at 120-130 days compared with controls. From 120 days onward, VtrFBM was 35-55% lower in experimental fetuses than in controls. Influx of lung liquid during FBM was 87% lower in experimental fetuses than in controls. Vtrapnea, tracheal pressure, and amniotic sac pressure were not significantly altered by oligohydramnios. Our tracheal flow rate data suggest that transient changes in lung liquid volume during periods of FBM and periods of apnea were diminished by oligohydramnios. We conclude that the primary factor in the etiology of oligohydramnios-induced lung hypoplasia is not an inhibition of FBM (as measured by tracheal pressure fluctuations) or a reduction in amniotic fluid pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Altered cardiovascular reflex responses during positive pressure breathing

Cardiovascular responses during hyperinflation produced by positive end-expiratory pressure (PEEP) are considered to be reflexly influenced by pulmonary mechanoreceptors. Numerous studies have indicated heart and vascular effects attributed to mechanical events and cardiopulmonary mechanoreflexes. Yet interactions of these modalities with the systemic baroreflexes are not clear. We examined aspects of these modulatory interactions by distinguishing changes in pulmonary, heart, and vascular responses during PEEP-hyperinflation before and after progressive elimination of chemo-, mechano-, and baroreflex influences in the closed-chest anesthetized rabbit. During respiratory alkalosis PEEP was imposed in increments of 2.5 cm H2O (range 0.0 to 7.5 cm H2O) before and during control of carotid intrasinus pressure and following aortic denervation and vagotomy. Heart rate responses during PEEP increased prior to aortic denervation, decreased following elimination of baroreflexes, and were abolished after vagotomy. The fall in mean arterial pressure (MAP) during PEEP was accentuated during elimination of the baroreflexes and ameliorated following vagotomy. Mean right atrial (MRAP), intrapleural (MIP), and right atrial transmural pressure increased during PEEP prior to vagotomy. Regression analyses of MAP versus MRAP and MAP versus MIP suggest that vagally receptors reflexly influence venous as well as systemic arterial vascular pressure. Conclusion indicate that when superimposed on mechanical events, cardiopulmonary mechanoreceptors and arterial baroreceptors effect conflicting facilitory reflex influences on heart and vascular responses during PEEP-hyperinflation.     

Patterned cardiovascular responses to sleep and nonrespiratory arousals in a porcine model

Patients with obstructive sleep apnea experiencemarked cardiovascular changes with apnea termination.Based on this observation, we hypothesized that sudden sleep disruptionis accompanied by a specific, patterned hemodynamic response, similarto the cardiovascular defense reaction. To test this hypothesis, werecorded mean arterial blood pressure, heart rate, iliac blood flow andvascular resistance, and renal blood flow and vascular resistance infive pigs instrumented with chronic sleep electrodes. Cardiovascularparameters were recorded during quiet wakefulness, duringnon-rapid-eye-movement and rapid-eye-movement sleep, and duringspontaneous and induced arousals. Iliac vasodilation (iliac vascularresistance decreased by 29.6 ± 4.1% of baseline) associatedwith renal vasoconstriction (renal vascular resistance increased by10.3 ± 4.0%), tachycardia (heart rate increase: +23.8 ± 3.1%), and minimal changes in mean arterial blood pressure were themost common pattern of arousal response, but other hemodynamic patternswere observed. Similar findings were obtained in rapid-eye-movementsleep and for acoustic and tactile arousals. In conclusion, spontaneousand induced arousals from sleep may be associated with simultaneousvisceral vasoconstriction and hindlimb vasodilation, but the responseis variable.