Effect of infant sleeping position on sleep spindles

Sleep spindles play an active role in inducing and maintaining sleep and may affect arousal by blocking the transmission of external stimuli through the thalamus to the cortex. Previously we have demonstrated that sleeping in the prone position impairs arousal in infants at 2-3 months of age, but not at 5-6 months. We aimed to examine if sleeping position and postnatal age affected duration and/or density of sleep spindles. Twenty-one healthy term infants were studied using daytime polysomnography at 2-3 months and 16 were again studied at 5-6 months. Infants slept both prone and supine at each study. The mean duration of non-rapid eye movement (NREM) sleep was not different between the two studies in either position. At 2-3 months both spindle density (P < 0.001) and proportion of NREM sleep (P < 0.025) with spindles were significantly greater in the supine than in the prone position. At 5-6 months spindle duration was longer in the supine than in the prone position (P < 0.03). Spindle density in the supine position was not different between the two studies, however, when infants slept prone, it was significantly increased at 5-6 months compared with 2-3 months (P < 0.001). Arousal threshold was not correlated with either spindle density or percentage of NREM sleep with spindles in either position at either study. In this study spindle density and the percentage time spent with spindles were not well correlated with infant arousability, and hence may not be able to be used as markers of depressed arousal responses in infants.     

Reliability of orthostatic responses in healthy men aged between 65 and 75 years

The purpose of this study was to investigate the short-, medium- and long-term reproducibility of cardiovascular responses during 90 degrees head-up tilt (HUT) in healthy older men. Twenty-eight healthy male subjects aged 69 (95% confidence intervals, 68-70) years participated in the study. Eight subjects underwent duplicate 90 degrees HUT tests on consecutive days, while 20 subjects underwent four 90 degrees HUT tests performed at baseline, and after 1 week, 1 month and 1 year. Following a 20-min supine resting period, each subject was rapidly tilted to the upright vertical position (90 degrees HUT) and remained in that position for 15 min. Beat-by-beat recordings of mean (MAP), systolic (SBP) and diastolic (DBP) pressures were made via Finapres, while heart rate (HR) was monitored continuously from an electrocardiogram. No significant test-retest differences (P > 0.05) were observed for the changes in HR, MAP, SBP or DBP during 90 degrees HUT. These measurements demonstrated high reproducibility (intraclass correlation coefficient, r = 0.91-0.99, P < 0.05). The supine resting and tilted HR, MAP, SBP and DBP over the 1-week, 1-month and 1-year period were not significantly different (P > 0.05) from baseline, and demonstrated high reproducibility (intraclass correlation coefficient, r = 0.82-0.98, P < 0.05). The results of this study demonstrate that in healthy older men, cardiovascular responses during orthostasis are highly reproducible, and this reproducibility is maintained over a 12-month period. These findings demonstrate that the 90 degrees HUT test offers a reproducible method of monitoring longitudinal orthostatic responses in healthy older men.     

Increased cardiac autonomic responses to auditory challenges in swaddled infants

STUDY OBJECTIVES: When infants have been swaddled and sleep supine, their risk of dying from sudden infant death syndrome (SIDS) is reduced with an odds ratio of 0.64 to 0.69. Alternatively, the risk for SIDS in swaddled infants shows a 3-fold increase in the prone position. The protective role of swaddling during supine sleep has remained unexplained. This study was designed to evaluate the effects of swaddling on cardiac reactivity to auditory stimuli during sleep in both the prone and the supine position. DESIGN: Thirty healthy infants with a median age of 11 weeks (range 8 to 15 weeks) were studied polygraphically for 1 night while sleeping successively prone and supine, or vice versa. The infants were studied while swaddled and nonswaddled in both positions. Heart rates were studied during rapid eye movement sleep, before and after exposure to 90 dB(A) of white-noise. RESULTS: Ten infants were excluded from the study because they woke up during the position change or the auditory challenge. Before the administration of the noise stimulus, swaddling decreased values of basal heart rates in the supine position only (P = .049). Following swaddling, the values of basal heart rate were significantly lower in the supine than in the prone position (P = .003). Auditory challenges were followed by a greater increase in heart rate when the supine sleeping infants were swaddled than when not swaddled (P = .018). When swaddled, beat-to-beat heart-rate variability increased following auditory stimulation in the supine position only (P = .012). CONCLUSION: When sleeping supine, swaddled infants had greater cardiac autonomic changes in response to noise challenges than when they were not swaddled.     

Effects of age and sleeping position on arousal from sleep in preterm infants

STUDY OBJECTIVES: Preterm infants are at increased risk of sudden infant death syndrome (SIDS). We investigated whether the prone sleeping position impaired arousal from sleep in healthy preterm infants and whether this impairment was related to cardiorespiratory variables, temperature or postnatal age. DESIGN: Longitudinal SETTING/PARTICIPANTS: 14 healthy preterm infants (mean 32 +/- 0.4 weeks) were studied using daytime polysomnography on 4 occasions: 36-38 weeks postconception age, 2 to 3 weeks postterm, 2 to 3 months postterm, and 5 to 6 months postterm. Interventions: N/A. MEASUREMENTS: Multiple measurements of arousal threshold (cm H2O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep and quiet sleep when infants slept both prone and supine. RESULTS: Arousal thresholds were significantly higher in both AS and QS when infants slept prone at 36 to 38 weeks postconception age and 2 to 3 months postterm but not at 2 to 3 weeks or 5 to 6 months postterm. These increases were independent of any sleep position-related changes in either rectal or abdominal skin temperature, respiratory rate, oxygen saturation or heart rate. CONCLUSIONS: At the age when the risk of SIDS is highest, the prone position significantly impairs arousal from both active sleep and quiet sleep in healthy infants born prematurely. This impairment in arousability occurred with no clinically significant changes in cardiorespiratory parameters or body temperature. Decreased arousability from sleep in the prone position may explain its role as a risk factor for SIDS.     

Carotid-cardiac baroreflex function does not influence blood pressure regulation during head-up tilt in humans

The influence of the carotid-cardiac baroreflex on blood pressure regulation was evaluated during supine rest and 40 degrees head-up tilt (HUT) in 9 healthy young subjects with and without full cardiac vagal blockade. The carotid baroreflex responsiveness, or maximal gain (G(MAX)), was assessed from the beat-to-beat changes in heart rate (HR) and mean arterial pressure (MAP) by the variable neck pressure and suction technique ranging in pressure from +40 to -80 Torr, with and without glycopyrrolate (12.0 +/- 1.0 microg/kg body weight; mean +/- SE). In the supine position, glycopyrrolate increased the HR to 91 +/- 3 bpm, from 54 +/- 3; MAP to 89 +/- 2 mmHg, from 76 +/- 2; and cardiac output to 6.8 +/- 0.3 l.min(-1), from 4.9 +/- 0.3 (P < 0.05). The G(MAX) of the carotid baroreflex control of HR was reduced to -0.06 +/- 0.01 bpm.mmHg(-1), from -0.30 +/- 0.02 (P < 0.05) with no significant effect on the G(MAX) of the carotid baroreflex control of MAP. During HUT the carotid baroreflex control of MAP was unchanged, though the G(MAX) of the carotid baroreflex control of HR was increased (P < 0.05). During HUT, central blood volume, assessed by electrical thoracic admittance, and total vascular conductance were decreased with and without glycopyrrolate. Furthermore, glycopyrrolate reduced G(MAX) of the carotid baroreflex control of HR during HUT (P < 0.05) with no significant effect on G(MAX) of the carotid baroreflex control of MAP. These data suggest that during supine rest and HUT-induced decreases in central blood volume, the carotid baroreflex control of HR is mediated primarily via parasympathetic activity. Furthermore, the maintenance of arterial blood pressure during postural stress is primarily mediated by arterial and cardiopulmonary reflex regulation of sympathetic activity and its effects on the systemic vasculature.     

Comparison of postnatal development of heart rate responses to trigeminal stimulation in sleeping preterm and term infants

Autonomic dysfunction has been regarded as a possible cause of the sudden infant death syndrome (SIDS) and it has been suggested that preterm infants, who are at a greater risk of SIDS than term infants, may have immature autonomic control. Our aim was to compare the maturation of cardiac autonomic control during sleep in preterm and term infants by examining heart rate responses to arousing and non-arousing trigeminal stimuli. Preterm infants (n = 15) and term infants (n = 24) were studied longitudinally with daytime polysomnography. Air-jet stimulation of the nares was delivered in both active sleep (AS) and quiet sleep (QS), and heart rate (HR) changes recorded for both arousal and non-arousal responses. Changes in HR (DeltaHR%) were calculated as the relative differences between baseline HR (BHR) and either MaxHR (arousal) or MinHR (non-arousal). Comparisons of HR changes between sleep states and postnatal ages were made with two-way anova for repeated measures and between groups with two-way anova. The increase in HR (DeltaHR%) was greater in term than preterm infants (P < 0.05), but only at 2-3 weeks corrected postnatal age (CPA). In preterm infants, there were no differences in BHR between sleep states, whereas in term infants, BHR was higher in AS than in QS at 2-3 weeks and 2-3 months of age. The smaller DeltaHR% to arousing stimuli in preterm infants compared with term infants at 2-3 weeks suggests that cardiac sympathetic activity in preterm infants may be lower than in term infants. This mechanism may account for the increased risk for SIDS of preterm infants.     

Arousal responses to somatosensory and mild hypoxic stimuli are depressed during quiet sleep in healthy term infants

STUDY OBJECTIVES: To compare arousal responses to somatosensory and hypoxic stimuli in sleeping human infants and to determine whether sleep state and postnatal age exerted similar changes in these arousal responses. DESIGN: We delivered somatosensory (nasal air-jet) stimulation and mild hypoxia (15% oxygen) to 10 healthy term infants aged 2 to 4 weeks, 2 to 3 months, and 5 to 6 months during identified sleep states. Hypoxic challenges were terminated at arousal, when the oxygen saturation fell below 85%, or at 5 minutes (failure to arouse). RESULTS: Infants failed to arouse to a greater percentage of hypoxia tests during quiet sleep (QS) than during active sleep (AS) at 2 to 3 months and 5 to 6 months of age (P < 0.01). Infants failed to arouse to a greater percentage of hypoxic challenges during QS at 2 to 3 months and 5 to 6 months than at 2 to 4 weeks of age. Arousal latency to hypoxia was significantly longer in QS than in AS at each study age; however, arousal latency was not affected by postnatal age. Arousal thresholds to somatosensory stimulation were significantly greater in QS than in AS, except at 2 to 4 weeks of age. In AS, arousability to the air-jet was greater at 2 to 3 months compared to 2 to 4 weeks of age (P < 0.05); in QS it was lower at 5 to 6 months compared to 2 to 4 weeks of age (P < 0.05). Arousal latency to hypoxia and arousal thresholds to air-jet stimulation were not correlated within infants. CONCLUSION: We conclude that arousal responses of infants to somatosensory and respiratory stimuli are similarly affected by sleep state and postnatal age. Infants are less arousable to both stimulus modalities in QS than in AS, and less arousable at 5 to 6 months of age than at 2 to 4 weeks in QS.     

Sleep position alters arousal processes maximally at the high‐risk age for sudden infant death syndrome

An impaired ability to arouse from sleep may play an important role in the pathogenesis of sudden infant death syndrome (SIDS). This study aimed to investigate the effects of prone sleeping on the nature of both induced and spontaneous arousal responses in infants. Thirteen healthy term infants were studied longitudinally at 2–4 weeks, 2–3 months and 5–6 months postnatal age. A pulsatile jet of air to the nostrils was used to induce arousal from both active sleep and quiet sleep in both prone and supine positions. For each stimulus, arousals were classified as sub‐cortical activations and cortical arousals, scored using physiological and electroencephalogram changes and expressed as a percentage of the total number of arousals. Spontaneous arousals were similarly analysed. Increased proportions of cortical arousals, hence decreased proportions of sub‐cortical activations, were observed in the prone position at 2–3 months. This distinct peak in the proportion of cortical arousals occurred regardless of sleep state and regardless of whether the arousal occurred spontaneously or was induced by air‐jet stimulation. The nature of arousal responses in healthy term infants is altered in the prone sleeping position at 2–3 months after birth, the age where SIDS incidence is highest. We postulate that a greater propensity for cortical arousal may be a protective mechanism to promote complete arousal in a vulnerable sleeping position and/or a vulnerable period of maturation. Inadequate or incomplete cortical arousals may explain the increased risk of SIDS associated with the prone position at this age.     

Age-related changes in control of blood pressure and heart rate during sleep in the rat

STUDY OBJECTIVES: The aim of this study was to determine age-related changes in the control of mean arterial pressure (MAP) and heart rate (HR) during sleep, and its relationship to the baroreflex in aging. DESIGN: MAP, HR, body temperature (TP), spontaneous activity (ACT), and sleeping/waking duration were monitored for 24 hours in groups of young (10-12 wk old) and old (23-24 mo old) rats. SETTING: The sleep laboratory at the University of Tokushima. PARTICIPANTS: Subjects were 8 young (10-12 wk old) and 7 old (23-24 mo old) Wistar rats. INTERVENTIONS: Reflex control of HR was evaluated by examining various pressure responses to an intravenous bolus injection of phenylephrine and sodium nitroprusside. MEASUREMENTS AND RESULTS: MAP and TP were recorded by a radiotelemetry system. HR was detected from the AP signal. ACT was counted by a photo-sensor system. In the case of old rats, the sensitivity of baroreflex control of HR was significantly depressed, and the spontaneous increase of MAP and HR during REM sleep and the MAP drop at the end of REM sleep were significantly enhanced. The old rats showed no large deterioration of the circadian profiles of MAP, HR, TP, and the amount of sleep. CONCLUSIONS: The baroreflex dysfunction is considered to appear in an early stage of the aging process, and to affect the control of MAP and HR during sleep.     

Norepinephrine and epinephrine responses during orthostatic intolerance in healthy elderly men

In young individuals, orthostatic intolerance is associated with marked increases in plasma epinephrine (EPI) concentrations and attenuated rises in plasma norepinephrine (NE) concentrations. This study investigated the cardiovascular, EPI and NE responses of healthy elderly males during orthostatic stress. Twelve men (68 +/- 1 yr) with a recent history of orthostatic hypotension and who exhibited orthostatic intolerance (HYPO) during 90 degrees head-up tilt (HUT) were compared with 12 men (69 +/- 1 yr) without a history of orthostatic hypotension and who remained normotensive (NORMO) throughout 90 degrees HUT. Beat-by-beat recordings of heart rate (HR), mean (MAP), systolic (SBP), diastolic (DBP), and pulse (PP) pressures were made throughout 90 degrees HUT. Blood samples obtained during supine rest and 90 degrees HUT were analyzed for changes in EPI and NE concentrations, hematocrit, hemoglobin and plasma volume. Compared to supine rest, orthostatic intolerance was characterized by significant reductions (p < 0.0001) in MAP, SBP, DBP, and PP. The HR, MAP, SBP, DBP, and PP at the termination of 90 degrees HUT was significantly lower (p < 0.0001) for HYPO than NORMO. The 90 degrees HUT position resulted in significant increases (p < 0.01) in NE for both HYPO and NORMO, with the rise in NE significantly lower (p < 0.05) in HYPO. There were no differences between groups regarding EPI concentrations at the termination of 90 degrees HUT. These results suggest that the magnitude of arterial pressure (AP) reduction does not influence the EPI response during orthostasis in healthy elderly men. However, marked reductions in AP, leading to orthostatic intolerance, are associated with inadequate increases in NE in these individuals.     

Spontaneous arousability in prone and supine position in healthy infants

STUDY OBJECTIVE: Compared with control infants, those who will be future victims of sudden infant death syndrome (SIDS) show a decreased arousability during sleep, with fewer cortical arousals and more-frequent subcortical activations. These findings suggest an incomplete arousal process in victims of SIDS. Prone sleep position, a major risk factor for SIDS, has been reported to reduce arousal responses during sleep. The present study was undertaken to evaluate whether the prone sleep position impairs the arousal process in healthy infants. METHODS: Twenty-four healthy infants were studied polygraphically during 1 night; 12 infants regularly slept supine and 12 infants regularly slept prone. Infants were matched for sex, gestational age, and age at recording. Arousals were differentiated into subcortical activations or cortical arousals, according to the presence of autonomic and/or electroencephalographic changes. Frequencies of subcortical activations and cortical arousals were compared in the prone- and the supine-sleeping infants. RESULTS: Compared with supine sleepers, prone sleepers had significantly fewer cortical arousals during rapid eye movement (REM) sleep (p = .043). There were no significant differences in cortical arousals between the 2 groups during non-REM sleep. No significant differences were seen in the frequencies of subcortical activations during both REM and non-REM sleep between supine and prone sleepers. The ratio of cortical arousal to subcortical activation showed no significant differences between the prone and the supine sleepers. CONCLUSIONS: Prone sleep position decreased the frequency of cortical arousals but did not change the frequency of subcortical activations, as has been previously found in SIDS victims. These results suggest specific pathways for impairment of the arousal process in SIDS victims.     

Decreased tolerance to orthostatic stress in diabetics

Cardiovascular responses to head up tilt (HUT) were investigated in chronic diabetics (having disease of 8 to 10 years duration) and in control subjects. The parameters recorded were heart rate (HR), blood pressure (BP), forearm blood flow (FABF) and forearm vascular resistance (FAVR). Recordings were made first in the supine position, next after HUT, and thirdly in the recovery period after return to the supine position. Normal subjects responded to HUT by a marked increase in HR (P less than 0.001), decrease in FABP (P less than 0.001) and increase in FAVR (P less than 0.001). The diastolic blood pressure (DBP) and mean blood pressure (MBP) showed appreciable increase (P less than 0.001, P less than 0.01 respectively) without significant fall in systolic blood pressure (SBP). The maximum alteration in cardiovascular responses was observed immediately after HUT (within 15 sec). The cardiovascular responses to HUT in diabetics were found to be significantly impaired compared to control subjects. The impairment of cardiovascular responses in diabetics in indicative of autonomic neuropathy which can be detected by these tests before the development of clinical signs of the neuropathy.     

Cardiac autonomic characteristics in infants sleeping with their head covered by bedclothes

The risk of Sudden Infant Death Syndrome is increased in infants sleeping with their head covered by bedding items. This study was designed to evaluate cardiac autonomic nervous controls in infants sleeping with the head covered by bedclothes. Sixteen healthy infants with a median age of 12 weeks (range 9-13 weeks) were recorded polygraphically for one night. While they slept in their usual supine position, a bedsheet was placed over their head for about 45 min. All infants were challenged with the head covered and with the head free during both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Sleep, breathing and heart rate (HR) characteristics were recorded simultaneously, together with rectal and pericephalic temperatures. In both head-free and head-covered conditions, autoregressive spectral analysis of HR was evaluated as a function of sleep stages. During the head-covered periods, parasympathetic tonus decreased and sympathetic activity increased in both REM and NREM sleep. Compared with the head-free periods, the head-covered sleep periods were characterized by greater rectal (P = 0.012) and pericephalic temperatures (P = 0.002). Covering the infant's head with a bedsheet was associated with significant changes in autonomic balance. The finding could be related to an elevation in temperatures within the infant's microenvironment.     

Interactions between sleeping position and feeding on cardiorespiratory activity in preterm infants

Infants sleeping in the prone position are at greater risk for sudden infant death syndrome (SIDS). Sleep position-dependent changes in cardiorespiratory activity may contribute to this increased risk. Cardiorespiratory activity is also affected by feeding. Twenty prematurely-born infants were studied at 31-36 weeks postconceptional age while sleeping in the prone and supine positions. Heart rate, respiratory rate, and patterns of variability were recorded during interfeed intervals, and effects of position and time after feeding were analyzed by repeated measures analyses of variance. There were significant effects of both sleeping position and time after feeding. Heart rate is higher and heart period variability is lower in the prone position, and the effects of sleeping position on cardiac functioning are more pronounced during the middle of the intrafeed interval. In preterm infants, autonomic responses to nutrient processing modulate the cardiorespiratory effects of sleeping position. Prone sleeping risk may vary with time after feeding.     

Of sleep state and postnatal age on arousal responses induced by mild hypoxia in infants

STUDY OBJECTIVES: It has been suggested that mild hypoxia may not be a potent stimulus for arousal during sleep in infants because infants frequently fail to arouse from quiet sleep (QS). Our aim was to characterize arousal responses of sleeping infants in both active sleep (AS) and QS under normoxic and mildly hypoxic (15% O2) conditions over the first 6 months of life. PARTICIPANTS: Five healthy term and 6 healthy preterm infants were each studied at 2 to 5 weeks, 2 to 3 months, and 5 to 6 months postterm. All infants underwent daytime polysomnography during which nasal airflow was monitored using a purpose-built pneumotachograph. All infants were studied under both normoxic (21% O2) and hypoxic (15% O2, balance N2) conditions (presentation order randomized) in each sleep state at each study age. Tests were terminated at arousal, O2 saturation falling below 85%, or 5 minutes (failure to arouse). MEASUREMENTS: Probability of failure to arouse and mean arousal latency were compared between each experimental condition, with each infant serving as its own control. RESULTS: Infants aroused more frequently under hypoxic conditions than under normoxic conditions. Overall, arousal latencies were shorter during hypoxia compared to normoxia in both sleep states at each age. Arousal latencies were longer in QS compared to AS in both hypoxic and normoxic conditions. CONCLUSION: In sleeping infants, mild hypoxia serves as a stimulus for arousal in both AS and QS. Of particular significance is our finding that arousal from AS is readily elicited by mild hypoxia.     

Sleeping position and upper airways bacterial flora: relevance to cot death.

The hypothesis that the prone sleeping position is associated with accumulation of upper airways secretions and increased bacterial growth was investigated in adults. Ten subjects with upper respiratory tract infection lay prone for one hour and then supine for one hour. Nasal swabs after the prone period yielded higher bacterial counts than swabs obtained after the supine period. This result could be relevant to sudden infant death syndrome (SIDS), as infants who sleep in the prone position are at increased risk of SIDS and one theory is that death is caused by toxins produced by bacterial overgrowth in the upper respiratory tract following a viral infection.     

"Back to sleep" and unexplained death in infants

OBJECTIVE: Investigation of body position in infants with sudden and apparently unexplained death. Determination of the upper airway space of the infants in different positions by computed tomography (CT) scan. Comparison of the CT scan, the body position at death scene, and the autopsy results. DESIGN: Prospective investigation on all infants referred to a specialized center investigating abrupt and apparently unexplained death of infants. SUBJECTS: Full-term infants with sudden and clinically unexplained death. Four extra infants studied at different postmortem times to verify absence of change in measurement in postmortem CT scan over time. DATA COLLECTED: Position of infant when found dead. CT scan of upper airway in 3 positions (prone face down, prone head rotated, supine nose up), presence or absence of upper airway obstruction, level and length of the obstruction, presence or absence of cause of death, and presence or absence of small maxillomandibular complex at autopsy. RESULTS: Twenty-seven children had unexpected crib deaths (17 of them determined to be sudden infant death syndrome at autopsy). Fourteen children were found dead in the prone position; for 8 of them, this was their normal sleeping position. Airway occlusion behind the base of tongue was seen on CT scan in 24 of the 27 infants (89%) when placed prone head down; in 13 (48%) when placed prone with the head rotated to the side, and in 5 (18%) infants in the supine position. Four infants had mild facial dysplasia and had been found dead in the supine position; in 3 of them, sudden infant death syndrome was found to be the cause of death. The stability of CT scan findings over time was demonstrated after death in 3 different body positions. CONCLUSION: Supine sleeping position may not be necessarily protective when small jaws are present, and sleeping position may also be a factor in abrupt deaths in infants even if "explained by autopsy."     

Arousal and ventilatory responses to hypoxia in sleeping infants: effects of maternal smoking

Our aim was to determine whether maternal cigarette smoking affects arousal and ventilatory responses to hypoxia in infants. Infants born to non-smoking (NS, n = 15) and smoking mothers (SM, n= 9) were studied at 2-5 weeks, 2-3 and 5-6 months. Ventilatory responses to 15% O(2) were determined preceding arousal. At each age and in both groups, infants aroused more frequently and earlier to hypoxia in active sleep (AS) than quiet sleep (QS). Arousal latency was longer in SM infants (in QS) at 5-6 months (P < 0.05). Baseline respiratory parameters were not different between groups, except that, at 2-3 months, SM infants had higher SP(O2) during AS than NS infants. Maternal smoking did not affect ventilatory responses preceding hypoxia-induced arousal in either sleep-state at any age. We conclude that mild hypoxia stimulates ventilation and arousal in infants up to 6 months and that arousability is depressed in SM infants at 5-6 months; however, ventilatory responses preceding arousal are not adversely affected by smoking.     

Modulation of plasma adrenomedullin by epinephrine infusion during head up tilt

We investigated whether head up tilt (HUT) with and without simultaneous epinephrine infusion modulate plasma adrenomedullin. We studied eight healthy male volunteers, using two 5 min 70° HUT trials: control (saline infusion) and intervention (epinephrine infusion, titrated to a dose which increased supine systolic pressure by 20% above resting values). Protocols were randomized and separated by 2 weeks. Cardiac function and systolic time intervals, recorded using a phonocardiograph microphone, included left ventricular ejection time (LVET), pre-ejection period (PEP), PEP/LVET and electromechanical systole (QS2). Compared to saline infusion, epinephrine increased supine adrenomedullin (3.2 ± 0.8 pmol/l, i.e., mean ± SEM, respectively), heart rate (HR) (+11.3 ± 2.6 bpm), systolic pressure (+18.4 ± 2.6 mmHg) but decreased supine LVET, LVET corrected for HR (LVETi) and QS2-time (all p = 0.004). Despite similar HUT induced thoracic fluid shifts, reflected by similar thoracic impedance changes, HUT-induced adrenomedullin increases were minimal in epinephrine-supplemented men in comparison to controls (+8% vs. 42%). During HUT, epinephrine infusion decreased only the LVET (p = 0.039). Our findings confirm that short-term HUT increases plasma adrenomedullin. They further suggest that with increased supine epinephrine levels (epinephrine infusion clamping systolic arterial pressure at 120% control level), supine cardiac performance rises to a level similar to that during HUT, while adrenomedullin is still elevated with HUT. This might be in accordance with a ‘dampening’ role of adrenomedullin during catecholaminergic cardiovascular stimulation. As epinephrine is used as a drug to treat cardiac arrest and ventricular arrhythmias, our results may have important clinical/emergency resuscitation applications.