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Biomedical subjects

M M Myers

Publications and source records attributed to M M Myers.

At least 19 recordsLinked to original sources

Sleeping position and electrocortical activity in low birthweight infants.

OBJECTIVE: To evaluate the effects of prone and supine sleeping positions on electrocortical activity during active (AS) and quiet (QS) sleep in low birthweight infants. DESIGN: Randomised/crossover study. SETTING: Infant Physiology Laboratory at Children's Hospital of New York. PATIENTS: Sixty three healthy, growing, low birthweight (birth weight 795-1600 g) infants, 26-37 weeks gestational age. INTERVENTIONS: Six hour continuous two channel electrocortical recordings, together with minute by minute behavioural state assignment, were performed. The infants were randomly assigned to prone or supine position during the first three hours, and positions were reversed during the second three hours. OUTCOME MEASURES AND RESULTS: Fast Fourier transforms of electroencephalograms (EEGs) were performed each minute and the total EEG power (TP), spectral edge frequency (SEF), absolute (AP) and relative (RP) powers in five frequency bands (0.01-1.0 Hz, 1-4 Hz, 4-8 Hz, 8-12 Hz, 12-24 Hz) were computed. Mean values for TP, SEF, AP, and RP in the five frequency bands in the prone and supine positions during AS and QS were then compared. In the prone sleeping position, during AS, infants showed significantly lower TP, decreased AP in frequency bands 0.01-1.0 Hz, 4-8 Hz, 8-12 Hz, 12-24 Hz, increased RP in 1-4 Hz, and a decrease in SEF. Similar trends were observed during QS, although they did not reach statistical significance. CONCLUSIONS: The prone sleeping position promotes a shift in EEG activity towards slower frequencies. These changes in electrocortical activity may be related to mechanisms associated with decreased arousal in the prone position and, in turn, increased risk of sudden infant death syndrome.

Cerebral Cortex↗

Cardiovascular responses to pacifier experience and feeding in newborn infants.

This study examined the effects of sucking on a pacifier immediately before feeding on cardiovascular responses to feeding. Twenty-eight bottle-feeding infants were studied at 12 to 40 hr of age. Blood pressure and heart rate measurements were made during three periods: Period 1-while infants rested in their cribs before a regularly scheduled feeding, Period 2-while being held by the feeder immediately before feeding, and Period 3-during the first 3 to 5 min of feeding. Half of the infants were given a pacifier during Period 2. Blood pressures and heart rates increased across the periods; however, increases in systolic blood pressure during feeding were reduced for the group of infants given a pacifier prior to feeding. We suggest that cardiovascular responses to feeding in infants are comprised of multiple elements. Most of the systolic blood pressure responses to feeding are elicited by sucking whereas the heart rate response is dependent on both sucking and nutrient intake.

Blood Pressure↗

Physiologic responses to cognitive challenge during pregnancy: effects of task and repeat testing.

Physiological responses to stress during pregnancy are believed to influence birth outcomes. Researchers have studied pregnant women in laboratory stressor paradigms to investigate these associations, yet normative data on cardiovascular and respiratory responses to laboratory challenge during pregnancy are not yet established. To begin to establish such normative data, this study examined the effects of task and repeat stressor exposure on reactivity in third-trimester pregnant women. Thirty-one healthy pregnant women (mean age=27 years; range 18-36) between the 33rd and 39th week of pregnancy, were instrumented for continuous electrocardiography, blood pressure (BP), and respiration data. Subjects rested quietly for a 5-min baseline and then performed both a mental arithmetic stressor and a Stroop color-word-matching task, each 5 min in length and each followed by a 5-min recovery period. The order of the tasks was counterbalanced. After each 5-min period, subjects rated the period on a 10-point stress scale. Averaged across task type and challenge period, systolic and diastolic BP and respiration rate increased significantly in response to cognitive challenge, but heart rate (HR) did not. When data were examined for task and period effects, the following results emerged: the Stroop task elicited significantly greater systolic BP and HR reactivity than the arithmetic task, yet subjects rated the arithmetic task as more stressful. Averaged across task type, subjects showed greater systolic BP reactivity during the second challenge period compared to the first. Finally, women's BP tended to drift upward and did not return to baseline during the first recovery period. These findings indicate that averaging data across tasks and periods can obscure the time course of response patterns that may be important in the study of associations between maternal stress and perinatal development, as well as in other research on reactivity to repeat stress exposure.

Adolescent↗

Breast-feeding and maternal cardiovascular function.

Two studies examined the effects of breast-feeding on maternal cardiovascular function. In the first experiment, groups of breast-feeding and bottle-feeding women were compared on preejection period (PEP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) recorded for 1-min periods before and during standard laboratory stressors. Compared with bottle-feeders, breast-feeders had higher CO throughout the session, and greater decreases in CO and increases in TPR during cold pressor. In the second experiment, HR and blood pressure (BP) were compared before and after one breast-feeding and one bottle-feeding session in a within-subjects design. Both feeding methods increased BP but decreased HR, and systolic BP was higher for the breast-feeding than the bottle-feeding condition. Both studies support the notion that breast-feeding alters maternal cardiovascular function, possibly through the actions of oxytocin.

Adaptation, Psychological↗

Olfactory based spatial learning in neonatal mice and its dependence on CaMKII.

Spatial learning and memory involves the ability to encode geometric relationships between perceived cues and depends critically on the hippocampus. Visually guided spatial learning has been demonstrated in adult animals. As infant animals rely heavily on olfaction, olfactory based spatial learning was assessed in infant mice. When 12-day-old pups were displaced from their nest, they learned within a few training trials to use the spatial pattern of odor cues to move back to the nest. However, mouse pups that over-expressed Ca2+/calmodulin-dependent protein kinase (CaMKII) in hippocampal neurons were impaired in olfactory based spatial learning.

Age Factors↗

Maturational changes in heart rate and heart rate variability in low birth weight infants.

To provide insight into the maturation of neural mechanisms responsible for variability in heart rate during quiet and active sleep, 6-hour continuous electrocardiographic recordings and simultaneous minute-by-minute behavioral activity state assignments were performed in 61 healthy, growing low birth weight infants. The infants weighed 795-1600 g at birth and ranged between 31-38 weeks in postconceptional age. During this age interval there was a decrease in heart rate during quiet sleep and an increase in both time domain and frequency domain measures of the variability in cardiac interbeat intervals. In quiet sleep, global variability, measured as SD of R-R intervals, increased in relation to age, as did higher frequency variability, measured as the square root of the mean of squared successive differences in R-R intervals. Developmental changes in the 0.5-2.0 Hz spectral power band of RR-interval variability, another measure of high frequency variability, paralleled the changes seen in the time domain measure. Evaluation of patterns of changes in the magnitude and direction of successive interbeat intervals provided evidence that the incidence of sustained accelerations or decelerations increased whereas the incidence of no change in consecutive RR-intervals decreased as infants matured. Among the various measures of heart rate variability, the incidence of sustained change and no change in successive interbeat intervals were most closely related to postconceptional age in both sleep states. The overall decrease in heart rate, increase in heart rate variability, and increase in the pattern of changes in interbeat interval with postconceptional age are consistent with the maturation of the autonomic cardio-regulatory activity from 31-38 weeks age.

Electrocardiography↗

Maternal stress responses and anxiety during pregnancy: effects on fetal heart rate.

This study examined the effect of an acute maternal stress response and anxiety on fetal heart rate. Seventeen healthy, 3rd-trimester pregnant women (mean age = 26 +/- 6 years) were instrumented for continuous electrocardiography, blood pressure (BP), respiration, and fetal heart rate (HR). Subjects completed the state anxiety subscale of the State Trait Personality Inventory (STPI), then rested quietly in a semirecumbent position for a 5-min baseline period, followed by either a 5-min arithmetic or Stroop color-word task. Over the entire 5-min stress period and when averaged across all subjects, the stressors led to significant increases in maternal systolic BP and respiratory rate but changes in maternal HR, diastolic BP, and fetal HR were not significant. However, when subjects were dichotomized into groups that had above or below average anxiety scores [ANX(+) and ANX(-)], both groups had similar respiration rate increases to the stressors, but the BP and fetal heart rate (FHR) responses were significantly different. Women in the ANX(-) group had significantly greater BP responses compared to women in the ANX(+) group whereas the fetuses of ANX(+) women showed significant HR increases and the fetuses of ANX(-) women exhibited nonsignificant decreases. These findings suggest that women's acute emotional reactivity during pregnancy can influence fetal HR patterns and that a stress-induced increase in maternal BP is not the primary signal by which a women's stress response is transduced to her fetus. The results are consistent with the hypothesis that maternal psychological variables may shape the neurobehavioral development of the fetus.

Adult↗

Gestational age related changes in cardiac dynamics of the fetal baboon.

To provide insight into the maturation of neural mechanisms governing fetal heart rate and rate variability, seven chronically instrumented fetal baboons were monitored under steady state conditions between 120 and 165 days gestation (term 175 d). Forty records of 24 h duration (5-7 records/fetus) were evaluated. For each fetus, heart rate decreased with gestational age (mean+/-SD, r = -0.530+/-0.324, P <0.05). In contrast, there were increases with age in markers of various components of autonomic control of fetal R-wave to R-wave interval (RRi) variability as reflected in a positive correlation with age for all fetuses of SD RRi (r = 0.656+/-0.347, P < 0.01), root mean squared differences in RRi (r = 0.686+/-0.223, P <0.05), and power at low frequency in the RRi spectrum (r = 0.800+/-0.161 P < 0.01). In each of the seven fetuses, scatter plots of RRi as a function of the prior RRi (Poincare plots) had increased dispersion around the median with gestational age (0.605+/-0.371, P<0.05). Additional measures of variability evaluated changes in RRi from one interval to the next (deltaRRi). The incidence of sustained deltaRRi changes, either decelerations or accelerations, rose with gestation (r = 0.920+/-0.057, P < 0.001) while the incidence of no detected deltaRRi changes (<+/-1 ms) diminished (r = - 0.649+/-0.364, P <0.05). Sequential decreases in fetal heart rate, increases in RRi variability and increases in changes in RRi and deltaRRi with age imply an overall maturation in autonomic cardio-regulatory control processes. Increases with gestation in measures of high frequency components of variability are compatible with enhanced parasympathetic modulation of fetal heart rate.

Animals↗

Body position, sleep states, and cardiorespiratory activity in developing low birth weight infants.

The objective of this study was to determine the effects of body position (supine vs prone) on cardiorespiratory activity during quiet and active sleep in growing low birth weight (LBW) infants. The effect of postconceptional age on cardiorespiratory activity in the two positions was also evaluated. Fifty-one healthy, growing, appropriate for gestational age LBW infants (795-1600 g), ranging from 26-37 weeks in gestational age, were evaluated. All subjects were enrolled in an ongoing study of the effects of quality of dietary energy on the rate and composition of weight gain. Infants were randomly assigned to the supine or prone position for the first 3 h of the 6-h studies; the position was reversed for the second 3 h. Continuous recordings of cardiorespiratory activity were performed along with simultaneous minute by minute assignment of behavioral sleep state. Measurements of heart rate (HR), heart period variability (RR-SD), respiratory rate (f), and respiratory variability (fSD) were made each minute. Low birth weight infants had higher HR and f and lower RR-SD and fSD in the prone position compared to the supine position, during both quiet and active sleep. With increasing postconceptional age, positional differences in HR increased during quiet sleep and differences in RR-SD increased during both sleep states. These data demonstrate systematic differences in cardiorespiratory control related to body position during sleep. We speculate that such positional differences are due to variations in autonomic control, and may, in turn, contribute to variations in susceptibility to sudden infant death syndrome.

Aging↗

Diurnal rhythms of fetal and maternal heart rate in the baboon.

To investigate the organization of diurnal rhythmicity during gestation, the relationship between daily cycles of maternal and fetal heart rate were measured in long-term studies of healthy chronically instrumented pregnant baboons. In each of six pregnancies, hourly mean values over a 168 h time series were obtained during a 7 to 10 day interval between 135 and 160 days of gestation. Data were modeled by a least squares fit to a cosine function with a period of 24 h. Hourly mean heart rate in the fetus ranged from 161 to 172 bpm (167.9+/-0.6 bpm), and the mother from 105 to 125 bpm (107.9+/-1.4 bpm). The amplitude of the daily fluctuations were 15 to 25 bpm for the fetuses and 25 to 60 bpm for the mothers. The relation between time series data and model estimates were significant (P < 0.001) in all cases with aggregate r2 = 0.747 for fetuses and 0.737 for the mothers. On average the time of day of the peak in fetal heart rate (15:05+/-0.3 h) was about 45 min after the maternal peak (14:21+/-0.4 h). This phase delay was significant (t = 2.63, P < 0.05). There was significant (P < 0.01) diurnal periodicity for each of six parameters used to assess different aspects of fetal heart rate variability with peak variability at night (23:00 to 2:00). Thus, during the latter third of pregnancy in both the maternal and fetal baboon 24 h periodicities of heart rate are present with peak rates in the midafternoon. The daily rhythms in fetal heart rate are linked with periodicities in maternal heart rate with a phase delay in the majority of cases. The synchrony of 24 h fluctuations in rate with parameters of rate variability is consistent with diurnal input into the fetal autonomic nervous system.

Amniotic Fluid↗

Cardiorespiratory responses to bidirectional tilts in infants.

Prior research in newborns has shown that head-up and head-down tilting elicits sustained increases and decreases in heart rate, respectively. Other studies in older infants have suggested that the pattern of heart rate responses to head-up tilting varies with risk for sudden infant death syndrome (SIDS). In this study, heart and respiratory rate changes following bidirectional tilting were recorded in sleeping infants on Day 1 or 2 of life, and during the period of maximum risk for SIDS, at 2 and 4 months of age. Newborns show increases in heart rate following 30 degrees head-up tilts and decreases in heart rate to 300 head-down tilting. Respiratory rates decreased to head-up tilting but did not change significantly to head-down tilting. While respiratory rate changes at 2 and 4 months of age are comparable to those of newborns, and decreases in heart rate to head-down tilting are similar across ages, sustained elevations in heart rate following head-up tilting are no longer apparent at the older ages. These results are consistent with the hypothesis that, during the period of maximum risk for SIDS, infants may have reduced ability to compensate for challenges that lead to decreases in blood pressure.

Age Factors↗

Postural differences in cardiac dynamics during quiet and active sleep in low birthweight infants.

To study the effects of body position (supine versus prone) on changes in cardiac inter-beat interval during quiet and active sleep, 6-h continuous electrocardiographic recordings and simultaneous minute-by-minute behavioural activity state assignments were made in 61 healthy, growing, low birthweight infants. The infants weighed 795-1600 g at birth and ranged between 30-38 wk in postconceptual age. Infants were randomly assigned to the supine or prone position for the first 3 h of each study; the position was reversed for the second 3 h. Higher heart rates and lower time and frequency domain measures of inter-beat interval variability were observed in the prone position as compared to the supine position, during both quiet and active sleep. In addition, an analysis of consecutive increases and decreases in the instantaneous heart rate revealed a lower incidence of sustained accelerations or decelerations in the prone position. Although consistent findings concerning inter-beat interval variability and sleeping position were obtained from all analytic techniques, the differences derived from analysis of consecutive inter-beat changes were the most robust. These differences in multiple measures of cardiac rate and rhythm between prone and supine positions suggest that autonomic control of the heart is altered by body position, the net effect on heart rate being increased sympathetic dominance.

Autonomic Nervous System↗

Implications of the kinetics of zidovudine in the pregnant baboon following oral administration.

Zidovudine (ZDV) therapy in pregnancy reduces mother-to-child transmission of HIV. The action of ZDV in the fetus is thought to be an important contributor to efficacy. Previous research in primates has demonstrated that continuous infusion of ZDV to the mother leads to sustained plasma concentrations in the fetus; however, it has not been determined what concentrations of ZDV are achieved in the fetus following oral administration. The pharmacokinetics of drug distribution to the fetus following oral administration of a 100-mg dose of ZDV to the mother are reported from 6 chronically catheterized baboons. The first order elimination half-life of ZDV from both the mother and fetus was approximately 1.2 hours. The area under the concentration-time curve for the fetus was 77% (r2 = 0.98; p < .001) that of the mother and the estimated peak drug levels in the fetus were 52% (r2 = 0.83; p < .01) those in the mother. The rapid transfer and short half-life of ZDV leads to a drug concentration-time profile that would not sustain levels in the fetus with dosing every 4 hours. After comparing these findings with existing data from pregnant and nonpregnant humans, it seems likely that current dose recommendations for ZDV in pregnancy would not maintain levels of the active intracellular metabolite of ZDV in all fetuses. This may explain in part the 8% failure rate of ZDV prophylaxis. The correlation between fetal and maternal plasma concentrations of ZDV would allow titration of dose based on maternal drug levels to achieve fetal levels within the therapeutic range.

Administration, Oral↗

Effects of sleeping position and time after feeding on the organization of sleep/wake states in prematurely born infants.

Epidemiologic studies provide strong evidence for the conclusion that sleeping in the prone position places infants at greater risk for sudden infant death syndrome (SIDS). Prior studies in newborn infants found that in the prone sleeping position there is less time awake and more quiet sleep, but little change in the amount of active sleep. To determine whether the effects of sleeping position on state distribution vary with time after feeding, we studied prematurely born infants in both the prone and supine sleeping positions. Sleep states were recorded each minute during interfeed intervals. Results demonstrate expected effects of sleep position on state distribution: prone sleeping is associated with a 79% increase in quiet sleep and a 71% decrease in time awake. While the decreases in time awake are seen throughout the interfeed interval, increases in quiet sleep in the prone position are found only within the first hour and again near the end of the interfeed interval. These results are consistent with the hypothesis that prone sleeping could increase risk for SIDS by altering the organization of sleep, and that time after feeding may play an important role in the expression of these effects.

Analysis of Variance↗

Diurnal rhythm of fetal behavioral state.

To test for the presence in utero of diurnal periodicity in the amount of time spent in organized behavioral states, seven records of 24-hour duration were obtained from each of five chronically instrumented fetal baboons between 144 and 158 days gestation (term = 175 days). Concordance of fetal breathing activity, heart-period variability, and electroencephalographic parameters were used to define two distinctive patterns of fetal physiological activities. One pattern was characterized as EEG activity dominated by tracé alternant, reduced heart-period variability, and fewer breaths in epochs of fetal breathing. This fetal behavioral state (1FB) is analogous to quiet sleep in infants. A second pattern was characterized by the relative absence of tracé alternant, increased heart-period variability, and fetal breathing activity. This fetal behavioral state (2FB) is analogous to active sleep. Cycles of these states were present 29% of time, with a duration of approximately 26 minutes and a 1.7:1 predominance of 2FB/1FB. Cosinor analysis across fetuses revealed a significant (p < .01) 24-hour periodicity of the time spent by the fetus in organized behavioral states, with a peak around 1400 (lights-on 0700 to 1900) and a peak-nadir fluctuation of 15%. These periodicities in the incidence of organized state were significant (p < .01) in three fetuses, and approached significance (< .09) in the two others. Data demonstrate a diurnal rhythmicity in fetal behavioral states, with less time spent in organized state at night than during the day.

Animals↗

Cardiovascular responses to feeding in the neonate during the first four days of life.

Prior work has demonstrated acute cardiovascular responses associated with breast and bottle feeding of newborn infants that consist of increases in both blood pressure and heart rate. This current study sought to determine if the amplitude of these responses is related to the age of the infant and/or the amount of nutrient ingested during the study period. Results show that the magnitude of the feeding responses does not change over the first four days of life. In a second study it was found that changes in systolic blood pressure during feeding are positively correlated with volume of nutrient intake during the initial phase of feeding (r = +0.75, p < 0.01). These results suggest that some of the individual variability in the increase in blood pressure during feeding is related to the amount of nutrient ingested. It is not known whether these differences are due to differences in sucking effort or other aspects of feeding efficiency.

Blood Pressure↗

Heart period variability and psychopathology in urban boys at risk for delinquency.

To examine associations between heart period variability (HPV) and psychopathology in young urban boys at risk for delinquency, a series of 697-11-year-old younger brothers of adjudicated delinquents received a standardized psychiatric evaluation and an assessment of heart period variability (HPV). Psychiatric symptoms were rated in two domains: externalizing and internalizing psychopathology. Continuous measures of both externalizing and internalizing psychopathology were associated with reductions in HPV components related to parasympathetic activity. These associations could not be explained by a number of potentially confounding variables, such as age, ethnicity, social class, body size, or family history of hypertension. Although familial hypertension predicted reduced HPV and externalizing psychopathology, associations between externalizing psychopathology and HPV were independent of familial hypertension. Psychiatric symptoms are associated with reduced HPV in young urban boys at risk for delinquency.

Blood Pressure↗

Placental transfer and fetal metabolism of zidovudine in the baboon.

Zidovudine (azidothymidine, AZT) is used in pregnancy to reduce mother to infant transmission of HIV. Understanding the disposition of AZT in the fetus is necessary to optimize therapeutic regimens directed toward the fetus. Recent studies in primates found similar steady-state levels of the glucuronide metabolite of AZT (AZT-glu) in the fetus to those in the mother, raising the question of whether the metabolite was of fetal or maternal origin. The objective of this study was to determine whether glucuronidation occurred in the fetal compartment and to quantify the placental and fetal clearances of AZT using the two-compartment model at steady state. Steady-state concentrations were obtained after paired maternal and fetal infusions of AZT in chronically catheterized pregnant baboons. During maternal infusion, the mean (+/-SE) fetal to maternal ratio of AZT was < 1 (0.84 +/- 0.06, p < 0.02), suggesting clearance of AZT in the fetus. Mean total maternal clearance of AZT was 725 +/- 49 mL/min and placental clearance was 36 +/- 4 mL/min, or approximately 5% of maternal clearance. Fetal clearance of AZT was estimated at approximately 15% of placental clearance. This suggests fetal nonplacental clearance is minimal compared with that in the mother, but does not preclude the fetus from actively contributing to the metabolite in the fetal circulation. During infusion of AZT to the fetus, the concentration of AZT-glu in the fetus was 7.0 +/- 0.8 times that in the mother. This is compelling evidence that glucuronide can be formed in the fetal compartment. Thus, fetal metabolism has an impact on the concentration of both AZT and AZT-glu in the fetal circulation.

Amniotic Fluid↗