Biomedical subjects

M M Myers

Publications and source records attributed to M M Myers.

At least 37 records · Page 2Linked to original sources

PubMed1997

A novel quantitative measure of Tracé-alternant EEG activity and its association with sleep states of preterm infants.

This study describes the application of a novel quantitative method for classifying patterns of EEG activity that are associated with the predominant sleep-states of newborn infants. Periods in which there are bursts of high-voltage slow wave activity in the EEG that alternate with periods of low-voltage activity are termed Tracé-alternant. During active or REM sleep. Tracé-alternant is absent and EEG activity is characterized by a variable mixture of frequencies including intermittent high frequency (10-20 Hz) activity superimposed on slower frequencies. Results show that an analytic method previously developed in fetal baboons for identifying EEG segments with and without Tracé-alternant successfully distinguishes homologous patterns of EEG activity in preterm infants. This method provides an excellent objective approach for monitoring changes in EEG patterns that are coincident with behaviorally defined sleep states.

Animals↗

PubMed1997

Effect of zidovudine on blood composition of the pregnant and fetal baboon.

OBJECTIVE: Our purpose was to assess the effect of intravenous zidovudine on placental function and fetal well-being. STUDY DESIGN: Eighteen chronically instrumented third-trimester pregnant baboons and their fetuses were studied after 4- to 48-hour infusions of zidovudine to 14 mothers (0.8 to 2.0 mg/kg/hr) and 6 fetuses (0.2 to 0.22 mg/kg/hr of maternal weight). Fetal and maternal pH and blood gases, hematocrit, blood cell counts, clinical chemistries, electrolytes, and hormones were measured before and after the infusions. RESULTS: In both mother and fetus no significant differences were found between values in the control periods and those after infusions of zidovudine in any of the index values measured. CONCLUSION: Administration of zidovudine from 4 to 48 hours in the baboon was associated with no significant change in any biochemical index values in the mother or fetus. Thus comparable exposure of the human fetus to zidovudine during labor is not expected to affect these index values of placental function and fetal well-being.

Acid-Base Equilibrium↗

PubMed1997

Cardiac autonomic control is inversely related to blood pressure variability responses to psychological challenge.

Blood pressure exhibits variability (BPV) at low (0.02- to 0.07-Hz), mid (0.07- to 0.15-Hz)-, and high (0.15- to 0.50-Hz) frequencies. Evidence suggests that BPV responses to challenge are inversely related to cardiac autonomic control. We tested this hypothesis by examining the BPV responses to psychological stressors in 22 normal subjects who differed in cardiac control, operationalized as resting heart period variability (HPV). HPV and BPV were measured noninvasively or a beat-to-beat basis. The stressors produced a significant increase in heart rate and a small but significant increase in diastolic blood pressure. As predicted, the changes in BPV in response to the stressors were inversely related to resting HPV. The results are interpreted in terms of a model of cardiovascular control that holds that BPV originates from feedforward effects of central control of the heart, feedback effects mediated through the baroreflexes, and direct sympathetic vascular effects.

Adult↗

PubMed1997

Blood pressure variability responses to tilt are buffered by cardiac autonomic control.

Variability in blood pressure (BPV) is influenced by vascular sympathetic drive as well as autonomic control of the heart. Evidence suggests that elimination of cardiac autonomic control, as measured by heart period variability (HPV), produces a reduction in BPV at rest but an increase in BPV during challenge. We recently showed that the BPV response to psychological challenge, which principally produces cardiac parasympathetic withdrawal, was inversely related to the subject's level of cardiac control. In the current study we examined the BPV response to orthostatic tilt, a sympathetic stressor. Subjects were 22 healthy men and women who differed in cardiac control due in part to differences in aerobic capacity. HPV and BPV were measured noninvasively on a beat-to-beat basis. Tilt produced significant increases in heart rate and diastolic blood pressure and a significant decrease in high frequency HPV. As predicted, changes in BPV in response to tilt were inversely related to resting HPV. Results are interpreted in terms of a model of cardiovascular control which holds that BPV originates from feedforward effects of central control of the heart, feedback effects mediated through the baroreflexes, and direct sympathetic vascular effects.

Adult↗

PubMed1997

Effects of combined carotid sinus and aortic depressor nerve denervations in neonatal rat pups.

Denervation of the major peripheral chemo- and barosensory organs of neonatal mammals is known to produce age-dependent effects on mortality and on respiratory and cardiovascular functions. In the current series of experiments, these phenomena were more fully characterized in the young rat. 8- to 9-day-old rats showed few effects of combined carotid sinus and aortic depressor nerve (CSAD) denervation. During the days following surgery, these animals maintained normal body temperatures, had relatively normal weight gain, little cardiorespiratory disruption, and none died. Denervation at earlier ages (postnatal days 3-4 or 0-1) resulted in considerable mortality, 24 and 59%, respectively. In addition, body temperatures were lower, and the weight gain was impaired in the denervated pups as compared with controls, and these effects were more severe in the CSAD nonsurvivors than in the survivors. Also, nonsurvivors had much more severe disruptions of cardiorespiratory patterns measured 24-96 h after surgery than did CSAD survivors. Twenty-four hours after surgery, pups that later died could be identified based on low heart rates and long inspiratory times. CSAD survivors maintained a pattern of moderate cardiorespiratory disruption as compared with controls. Finally, our results indicate that the additional stress of subcutaneous electrocardiography lead implantation and/or daily maternal separation for cardiorespiratory recording increased the mortality in the 3- to 4-day-old CSAD pups from 11 to 40%.

Age Factors↗

PubMed1996

Diurnal rhythms in cardiorespiratory function of the fetal baboon.

Diurnal periodicities of cardiorespiratory function were monitored between 144 and 156 days of gestation (term = 175 days) in six chronically instrumented fetal baboons. For each fetus, 5-11 days of electrocardiographic and tracheal fluid pressure data were summarized as hourly means of fetal heart rate (FHR), standard deviation of FHR, breath-to-breath interval (B-Bi) and percent time spent in fetal breathing activity (PFB). Summaries were evaluated by cosinor analysis to determine the least squares fit to a 24-h cycle. For all fetuses, FHR had a significant (P < 0.001) diurnal rhythm with peak to nadir fluctuations of 17.4 beats/min around a 24-h mean of 163.2 beats/min. The time of the peak FHR was similar across animals occurring in the mid-day between 10:49 h and 14:45 h. For each fetus, standard deviation of FHR also had a significant (P < 0.01) diurnal periodicity with highest values at night between 20:15 h and 02:04 h. The times of the acrophase for these heart rate parameters were correlated (R = 0.88, P < 0.02) across fetuses. Significant (P < 0.001) 24-h rhythms were found in four of six fetuses for B-Bi and five of six for PFB. These PFB rhythms accounted for a fluctuation of 14.4% around a mean of 36.9 +/- 4.5%. In contrast to heart rate, the acrophases of fetal breathing parameters were distributed throughout the entire 24-h cycle and not significantly correlated across fetuses. It is concluded that diurnal rhythms of fetal heart rate, which are synchronized with light/dark conditions in the environment, are evidence for a passive response or entrainment of fetal systems to maternal circadian influences. Alternately, the absence of synchronization across fetuses in daily rhythms of fetal breathing activity provides evidence for a functioning fetal pacemaker, and not simply the imposition of maternal rhythms on her fetus. This differential in the cardiac and breathing activity of the developing primate indicates that pathways for entrainment of fetal pacemaker function are subject to important maturational influences during late gestation.

Animals↗

PubMed1996

Parasympathetic control of heart period during early postnatal development in the rat.

Basal autonomic control of the heart period (HP) changes considerably during the early postnatal period in the rat. Although studies in the developing animal have examined the ability of the sympathetic branch to decrease HP during physiological challenge, few studies have examined the emerging capabilities of the parasympathetic branch to alter HP during early development. To determine the extent of parasympathetic control of HP in the young rat, we used a modified dive reflex procedure and electrical stimulation of the vagal nerve to examine the range of parasympathetic effects on HP in postnatal day 3-24 rats. Modified dive reflex manipulations produced maximal parasympathetically-mediated HPs that were longer just after birth and at weaning than at intervening ages. Direct vagal nerve stimulation studies revealed significant decreases with age in the HP at maximal vagal activation and in the intrinsic HP. The dynamic range, or difference between minimal and maximal parasympathetic effects on HP was similar across ages when assessed from the results of vagal stimulation. Nerve stimulations also revealed age-independent and relatively linear transfer functions relating parasympathetic stimulation frequency and HP during early life. Therefore, several parameters characterizing parasympathetic control of HP, including the dynamic range and transfer function, remain reasonably stable throughout the early postnatal period in the rat. These data provide a framework delineating the autonomic limits within which cardiac responses operate in the young rat. Knowledge of changes in these limits across time affords a firmer physiological basis for cross-age comparisons of autonomically-mediated cardiac changes.

Animals↗

PubMed1996

Zidovudine kinetics in the pregnant baboon.

The devastating impact of human immunodeficiency virus (HIV) infection during pregnancy has made the pharmacologic evaluation of potentially therapeutic agents of high priority. The results presented here are the maternal pharmacokinetics from a series of experiments to delineate more clearly the complex maternal-fetal pharmacokinetics and the effects of AZT in the chronically instrumented maternal and fetal baboon during both steady state intravenous infusion and oral bolus dosage regimens. Two results of major clinical importance were found. First, during pregnancy, both the clearance and volume of distribution of AZT were increased. Plasma clearance in the pregnant animals was 51 +/- 10 ml/min/kg compared with 37 +/- 2 ml/min/kg in the nonpregnant animals, and steady state volume of distribution was 3.7 +/- 1.21/kg compared with 2.2 +/- 0.61/kg. Second, with continuous intravenous infusion plasma drug concentrations were easily maintained in the therapeutic range, whereas with oral administration plasma concentration fell below therapeutic levels within 2 h of the dose being given. Because maternal plasma concentrations are a major determinant of drug concentration achieved in the fetus, an understanding of drug kinetics in pregnancy is of vital importance when making recommendations regarding optimal drug therapy during pregnancy to maximize the beneficial effect--the prevention of HIV infection in children.

Absorption↗

PubMed1996

Blood pressure and HR in the fetal lamb: relationship to hypoglycemia, hypoxemia, and growth restriction.

We examined blood pressure and heart rate (HR) in relation to glucose and arterial PO2 (PaO2) at approximately 121 days (early) and at approximately 140 days (late) gestation in 12 growth-restricted and 10 control fetal lambs. Mild growth restriction (relative to maternal weight) was produced by withdrawal of 25 ml/day of maternal blood during the second half of pregnancy (P < 0.05). Fetuses from this model are hypoglycemic during early and late gestation but hypoxemic only during late study. Mean systolic and diastolic pressures in the experimental group were approximately 8.0 mmHg lower than the corresponding values in controls at both studies (P < 0.05). Fetal HR (FHR) was 15.4 beats/min lower (P < 0.05) in 10 but was higher than control in 2 experimental fetuses that were also not growth restricted. There were significant correlations between late systolic pressure and HR and PaO2 (r = 0.54, P = 0.046 and r = 0.50, P = 0.049, respectively) and between FHR and blood pressure and birth weight/maternal weight (P < 0.05). We conclude that, in this model, fetal blood pressure and HR may serve as good indicators of hypoxemia and growth restriction.

Animals↗

PubMed1996

Effects of neonatal growth on adult blood pressures of borderline hypertensive rats.

We conducted this study to test the hypothesis that there are long-term effects of litter-size manipulations during the preweaning period on growth and adult blood pressure of rats. Litter size of genetically homogeneous borderline hypertensive rats, which were produced by cross-mating male Wistar-Kyoto rats with female spontaneously hypertensive rats, was manipulated from 10 to 16 days of age. In addition, a subset of males and females was castrated within the first 30 hours of life. Body weights were measured at several preweaning and postweaning ages, and tail-cuff blood pressures were recorded at 90 days of age. Intact and castrated pups of both sexes that were reared in small (n = 4) litters from 10 to 16 days of age gained nearly twice the weight of animals reared in large (n = 9 to 12) litters during this period. Intact males from small litters had significantly higher adult blood pressures than those from large litters. These long-term effects remained even in groups matched for adult weight and length. Neonatal castration of males completely blocked the consequences of litter-size manipulation on adult blood pressure, suggesting either an organizational or activational role for androgens. Neither intact nor neonatally castrated females exhibited differences in adult blood pressure as a function of litter-size manipulation.

Animals↗

PubMed1995

Methodological issues in coding sleep states in immature infants.

Thirty-five healthy, premature infants, ranging from 30-39 weeks postconceptional age, were observed continuously for 6 to 24 hr. Behavioral state and electroencephalographic patterns were coded for each minute. Using these data, three questions regarding coding of states of sleep were addressed: What is the concordance between behavioral codes and specific EEG patterns? Does the concordance between behavioral codes and EEG patterns change with postconceptional age? What range of error can be expected when observation periods shorter than 24-hr are used to estimate the daily distribution of quiet sleep (QS) and active sleep (AS)? With behavioral codes as the standard, concordances of EEG patterns for QS and AS were 72.5 and 92.1% respectively. With EEG patterns as the standard, behavioral codes for QS and AS agreed 83.0 and 88.9%. Agreement between behavioral codes and EEG patterns for QS increased with age. Finally, variation in estimates of the daily distribution of QS and AS decreased dramatically as the length of observation increased from 3 to 24 hr.

Arousal↗

PubMed1995

Preoperative cardiorespiratory trends in infants with congenital diaphragmatic hernia.

The objective of this study was to determine the cardiovascular and pulmonary adaptations of infants with congenital diaphragmatic hernia (CDH) from birth until delayed surgery through the use of continuous monitoring. Continuous cardiovascular (HR, heart rate variability [HR-SD], BP, blood pressure variability [BP-SD], and oxygen saturation) and ventilatory (minute volume, airway pressure, and effective compliance) measurements were made on-line, using a computerized whole-body plethysmograph-incubator (Vital-trends, VT1000), in nine ventilated infants with CDH. Data collection commenced at birth and continued until surgery. Minute mean values for each variable were recorded. Hourly means were computed from the minute means, averaged across infants each hour over the first 50 hours of life, and regressed against postnatal age. Results showed a significant increase in BP (P < .01), BP-SD (P < .05), HR-SD (P < .04), and pH (P < .02) versus postnatal age, and a decrease in PaCO2 (P < .04), FIO2 (P < .001), Alveolar-arterial oxygen gradient (P < .003), and oxygenation index (P < .002). Infants with CDH show cardiopulmonary trends over the first 2 days of life that are qualitatively similar to those of normal newborn infants. Deviation from these idealized patterns may identify an infant who is not responding satisfactorily to the given therapy and who may require alternative treatment modalities.

Adaptation, Physiological↗

PubMed1995

Consistency of heart rate and sympathovagal reactivity across different autonomic contexts.

Theories that psychophysiological reactivity constitutes a risk factor for coronary artery disease assume that reactivity is a consistent individual characteristic. We tested this assumption by measuring reactivity to three psychologically challenging tasks performed by 22 healthy subjects across different autonomic contexts produced by positional change. Dependent variables included heart rate (HR), low-frequency (LF; 0.04-0.15 Hz) and high-frequency (HF; 0.15-0.50 Hz) heart period variability, and the LF/HF ratio. HR (r = .44, p < .05) and LF/HF ratio (r = .48, p = .03) reactivity were modestly correlated across the different autonomic contexts, but HF and LF power reactivity were not. These findings suggest that HR reactivity to psychological challenge is a modestly consistent characteristic of individuals, despite differences in autonomic context. Although the same is true of cardiac sympathovagal balance, reactivity of HF and LF power were less consistent.

Adaptation, Physiological↗

PubMed1994

Behavioral states in the fetal baboon.

This study was designed to characterize behavioral states in the fetal baboon. Automated methods were developed and validated to recognize behavioral states based on relationships among three physiologic variables (EEG patterns, eye movements, heart period variability). Data included twelve 16-h records from 3 chronically instrumented fetal baboons at 0.8-0.9 of term. Randomly generated control records were used to differentiate occurrences of state from chance association of the variables. For 41.2 +/- 4.6% (mean +/- S.E.) of the time, the physiologic variables were synchronous and formed cycles of state with a mean duration of 34.4 min. Components of these cycles had mean +/- S.E. durations of 7.2 +/- 0.3 min for state 1FB (the analogue of quiet sleep in the human infant and state 1F in the human fetus), 20.7 +/- 1.2 min for the state 2FB (the analogue of active sleep in the human infant and state 2F in the human fetus), and 3.6 +/- 0.2 min for state transitions. For 24.6 +/- 2.4% of the time, the state variables exhibited coincidental, state-like agreements, that were not part of state cycles. Finally, for 34.3 +/- 2.7% of the time, there was no systematic agreement among the three variables. These data provide convincing evidence that organized behavioral states are present in the fetal baboon as early as 0.8 of term gestation.

Algorithms↗

PubMed1994

Brief interval heart period variability by different methods of analysis correlates highly with 24 h analyses in normals.

Heart period variability (HPV) measured from 24 h ECG recordings predicts mortality following myocardial infarction and may be a measure of cardiovascular health in the general population. Since epidemiologic evaluation of healthy people will require alternatives less intensive than 24 h recording, we investigated the relationship between HPV derived from 24 h and 5 min recordings, using two approaches for obtaining RR intervals. Template-matching (TM) algorithms were applied to 24 h ECG recordings from 41 normal subjects (mean age 35.7 +/- 13 years). Five min of ECG data during this 24 h period also were collected by an on-line microcomputer-based system for peak detection (PD) analysis. Intraclass correlations comparing the TM and PD approaches on the 5 min period were .80 or greater for all measures of HPV. Pearson correlation coefficients between the 5 min (TM) estimates and 24 h data and 5 min (PD) estimates and 24 h data exceeded .60 and .55, respectively, for all but one variable, with all p values < .05. Thus, in healthy adults, TM and PD approaches to HPV estimation from short segments of ECG data are highly consistent and the correlations between HPV obtained from brief intervals and 24 h measures were substantial, suggesting that assessment of HPV as a screening measure of cardiac autonomic control in healthy adults may be feasible.

Adult↗

PubMed1994

Patterns of fetal breathing in the baboon vary with EEG sleep state.

This report examines the hypothesis that the characteristics of breathing activity of the fetal baboon are modulated with respect to sleep state in a fashion similar to that observed in the human fetus. The pattern of fetal breathing activity was examined in relationship to electroencephalographic (EEG) sleep state in studies of six fetuses of chronically monitored pregnant baboons at 143-148 days of gestation (term, 175-180 days). Fetal breaths were defined by fluctuations of tracheal fluid pressure. EEG sleep states were defined with an automated method for discrimination of EEG patterns that are standard indices of quiet and active sleep in immature primates. During more than 250 h of recorded data, the fetuses spent on average 33.3 +/- 3.9% of time in EEG quiet sleep. In comparisons across state the fetuses spent significantly (P = 0.001) less time breathing during quiet than active sleep (49.5 +/- 6.8 vs. 69.0 +/- 3.8%). The inspiratory and expiratory time intervals of fetal breaths were not differentiated by EEG state but, the mean breath to breath interval was significantly (P < 0.001) longer in EEG quiet sleep. In addition to these differences in incidence and time interval of breaths, during epochs of breathing, there was a significantly slower rate, lower amplitude, and lower variability of rate of breathing in quiet sleep (all P-values < 0.02). Thus, periodic breathing activity in the fetal baboon is present in both quiet and active EEG sleep states. Sleep states have a powerful influence on patterns of fetal breathing in the non-human primate, directly comparable to the human fetus.

Animals↗

PubMed1994

Fetal hiccups in the baboon.

Bouts of hiccuping are recognized by pregnant women as distinct episodic movements of their fetuses. Ultrasound imaging of these fetuses has documented the occurrence of hiccups from early gestation through parturition. This study provides a systematic characterization of prenatal hiccuping in the fetal baboon (Papio species). Tracheal fluid pressure was recorded from 11 chronically instrumented fetal baboons for 21.5 +/- 7.3 consecutive days (mean +/- SD) over a range in gestation from 124 to 164 days (term 175 days). In an initial review of pressure recordings by visual inspection, hiccups were recognized as distinctive high-amplitude fluctuations in tracheal pressure that were readily discriminated from fetal breaths. Automated techniques were then developed and validated to detect hiccups and summarize their features. The mean hiccup amplitude was 23.0 +/- 3.1 mmHg, inspiratory time was 0.26 +/- 0.03 s, and expiratory time was 0.27 +/- 0.02 s. Each of these features discriminated hiccups from breaths (P < 0.001). Hiccuping incidence (1.8 +/- 0.4% of time), rate (26.2 +/- 6.2 min-1), bout duration (4.3 +/- 0.8 min), and the interval between bouts (3.35 +/- 0.60 h) were also different (P < 0.01) from breathing. These features of hiccups remained relatively constant over the latter third of gestation with the exception of an increase in duration of the expiratory time interval (r = 0.54, P < 0.01). Despite their vigorous nature, bouts of hiccuping were not associated with transitions in behavioral state. Moreover, the features of hiccups were not differentiated by state. Bouts of hiccuping recurred in a cyclic fashion, on average every 3-4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effect of innervation on heart rate response to mental stress.

Heart transplant recipients provide a useful model for study of the autonomic control of the cardiovascular response to mental stress. Utilizing the innervated native atrial tissue of heart transplant recipients as an internal control exposed to the same circulatory milieu as the denervated graft heart was exposed to, the effect of innervation on the heart rate response to a mentally stressful arithmetic task was examined in eight subjects. Compared with the graft, the innervated atrial tissue manifested a larger heart rate increase during the task, larger heart rate decrease after the task, and more rapid rate of change in heart rate during the task and recovery periods. Thus, cardiac denervation results in a chronotropic response to mental arithmetic-induced stress that is blunted and more gradual than that of the innervated heart but not completely eliminated. The cardiac chronotropic response to mental arithmetic stress is dependent on both humoral factors and, predominantly, its direct autonomic innervation.

Adult↗