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Biomedical subjects

R M Harper

Publications and source records attributed to R M Harper.

At least 91 records · Page 5Linked to original sources
PubMed1993

Minute-by-minute association of heart rate variation with basal heart rate in developing infants.

Particular types of heart rate variation are enhanced during periods of slow heart rate and diminished when heart rate is high. We examined how the correlations between heart rate and various types of heart rate variation developed in normal infants. Polygraphic recordings were obtained from 25 infants at 1 week and at 1, 2, 3, 4 and 6 months of age. Median heart rate and the extents of heart rate variation at three distinct frequencies were determined for each 1-minute epoch. Pearson's r was used to assess the correlation of median heart rate in each epoch with each of three types of heart rate variation. For each recording, correlations were assessed separately for quiet sleep, rapid eye movement (REM) sleep and waking. The maturational patterns of heart rate by heart rate variation correlations were strongly influenced by sleep-waking state and were dissimilar to those previously reported for correlations between cardiac and respiratory measures. The findings suggest dissimilar developmental patterns for autonomic and somatic motor systems, and include a discontinuity in autonomic development at approximately 1 month of age. We speculate that these trends reflect a change in the nature of sleep states as forebrain connections develop.

Aging↗
PubMed1993

Ventilatory CO2-induced optical activity changes of cat ventral medullary surface.

We examined neuronal activation of the ventral medullary surface (VMS) during hypercapnic challenges using optical recording procedures. With a coherent imaging probe, we assessed reflected 700-nm light from 18 VMS sites in 11 spontaneously breathing adult cats and from the suprasylvian cortex in two cats. Video frames were acquired during a baseline period, hypercapnic (3, 5, and 10% CO2 in O2) exposure, and recovery. Hypercapnic exposure elicited overall reflectance changes in all VMS sites, but no changes in the suprasylvian cortex. Light reflectance changes, suggesting altered neuronal activity, were reproducible, occurred as early as 30 s after CO2 exposure, and were dose dependent. The changes persisted approximately 20-25 min beyond the stimulus, but respiratory responses consistently recovered within 2-3 min. Although more rostral VMS sites tended to be associated with decreased activity and caudal regions with increased excitation, no uniform topographical organization was apparent across animals. The variability in VMS optical reflectance patterns across animals during CO2 stimulation may reflect the heterogeneous topographical distribution of responsive neurons in the structure.

Animals↗
PubMed1993

Optical imaging of the ventral medullary surface of cats: hypoxia-induced differences in neural activation.

Large-array optical recording procedures provide the potential to examine simultaneous activity of large numbers of neurons. We applied this technique to examine regional neuronal activation on the ventral medullary surface (VMS) of cats during hypoxic challenges. VMS was exposed through a ventral surgical approach in eight adult cats under pentobarbital sodium anesthesia. Arterial pressure, end-tidal CO2, costal diaphragmatic electromyograms, and electrocardiograms were continuously monitored. A coherent image conduit with 12-microns-fiber resolution was attached to a charge-coupled device camera and positioned over the VMS. Reflected 700-nm light was digitized continuously at 2- to 3-s intervals during baseline period, hypoxic (6, 9, and 12% O2 in N2) exposure, and recovery. Forty images within each epoch were averaged and subtracted from baseline. Regional differences within the image were determined by analysis of variance procedures (alpha = 0.05). In caudal VMS, hypoxic challenges with 12% O2 consistently induced a regional diminution in reflected light (increased neural activity) that was rapid in onset and persisted for approximately 20 min after termination of exposure, well beyond the duration of discernible ventilatory alterations. In contrast, the same challenge resulted in decreased neural activity of similar duration in rostral VMS areas. Challenges with lower inspired concentrations of O2 reversed the pattern of diminished neural activity in rostral regions and led to a dose-dependent increase in neural activity, a dependency also observed in caudal VMS. We conclude that caudal VMS neurons demonstrate a unidirectional dose-dependent response pattern to hypoxic stimuli, whereas rostral VMS regions exhibit a bidirectional response to increasing hypoxic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Development of heart rate dynamics during sleep-waking states in normal infants.

Previous studies show alterations in the dynamic patterns of cardiac rate in several "at-risk" populations, including apparently healthy infants who subsequently die of the sudden infant death syndrome. In the present study, we examined the maturation of cardiac rate dynamics in normal infants during sleep-waking states over the first 6 mo of life. Instantaneous changes in cardiac R-R intervals were examined in 12-h recordings of 24 normal full-term infants; each infant was recorded at 1 wk and at 1, 2, 3, 4, and 6 mo of age. Scatter plots, consisting of each cardiac R-R interval plotted as a function of the previous interval (Poincaré plots), were constructed for each sleep-waking state in each recording. Analyses of variance were performed on the dispersion of intervals after long and short R-R intervals. In neonates, Poincaré plots showed significantly more next-interval dispersion after a long R-R interval than after a short interval, a pattern similar to those observed in older infants and in healthy adults. However, between 1 wk and 1 mo of age, this pattern disappeared and returned gradually beginning at 2 mo of age. The scatter of points in Poincaré plots of infants 1 mo of age approached the patterns of at-risk populations, including infants who subsequently died of the sudden infant death syndrome. These patterns at 1 mo may be indicative of increased vulnerability in normal infants after the neonatal period.

Age Factors↗
PubMed1993

Interictal heart rate patterns in partial seizure disorders.

Epileptogenic mesial temporal damage may alter interictal autonomic patterning. Analysis of heart rate variability in 19 patients with complex partial seizures revealed cases of persistent, high-amplitude, 4 to 9 per minute fluctuations in heart rate during alert waking. This pattern was most pronounced in poor candidates for anterior temporal lobe resection (2/19). The 4 to 9 per minute heart-rate variability pattern may emerge following diffuse, extratemporal, or bilateral mesial temporal damage, which interferes with descending forebrain influences on cardiovascular regulation.

Adolescent↗
PubMed1993

Analysis of beat-to-beat heart rate changes during sleep-waking states in normal infants.

Summary measures of heart rate variation describe those aspects of heart rate change that can be averaged over relatively long periods of time. We examined the postnatal maturation of a dynamic feature of cardiac rate--the dependency of each beat-to-beat change in cardiac interbeat interval on the previous beat-to-beat change. In each sleep-waking state, the number of delta RR (the difference between two successive R-R intervals) 4msec was determined as a percent of the total number of intervals (delta RR > 4ms/total delta RR), and each pair of successive interval differences was categorized based on the directions of the two changes (whether they reflected increases or decreases in cardiac intervals). Analysis of variance was used to identify alterations in the proportion of interval differences exceeding the minimum over ages and sleep-waking states, and to describe developments in the temporal patterns of cardiac interval changes. At all ages, infants showed fewer beat-to-beat interval changes during waking than during either sleep state. In all states, older infants showed significantly more beat-to-beat cardiac interval changes and a higher proportion of sustained changes (intervals increasing or decreasing consistently over several beats) than did young infants. Furthermore, infants 2 months and younger showed significantly more sustained increases than decreases in interbeat intervals, indicating gradual declines in heart rate and rapid increases, while older infants showed the opposite pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiography↗
PubMed1992

Discharge dependencies of amygdala central nucleus neurons to the cardiac and respiratory cycle following local cocaine administration.

We examined dependencies of amygdala central nucleus neuronal discharge to the cardiac and respiratory cycles in freely behaving cats following local microinjection of cocaine (100 micrograms/0.2 microliter). Cross-correlation histograms showed cycle-by-cycle dependencies between neuronal discharge and the cardiac and respiratory cycles in 10 of 30 cells and 7 of 30 cells, respectively, during baseline periods. After cocaine delivery, the discharge rate of half of the central nucleus of the amygdala cells (16/30, 53%) were partly or completely inhibited in a reversible manner. Excluding cardiac- and respiratory-dependent neurons which ceased firing after cocaine, more than half (5/8) of the remaining cardiac and two-thirds (4/6) of respiratory-dependent neurons altered discharge dependencies following cocaine administration. Of the cells that did not exhibit cardiac and respiratory dependencies pre-cocaine, 2 of 20 developed cardiac correlations and 3 of 23 developed respiratory correlations following cocaine administration. We speculate that a portion of the cardiac and respiratory responses induced by cocaine may be mediated through the central nucleus of the amygdala.

Amygdala↗
PubMed1992

Patterns of beat-to-beat heart rate variability in advanced heart failure.

Diminished heart rate variability is associated with high sympathetic tone and an increased mortality rate in heart failure cases. We constructed Poincaré plots of each sinus R-R interval plotted against the subsequent R-R interval from 24-hour Holter recordings of 24 healthy subjects (control group) and 24 patients with heart failure. Every subject in the control group had a comet-shaped Poincaré plot resulting from an increase in beat-to-beat dispersion as heart rate slowed. No patient with heart failure had this comet-shaped pattern. Instead, three distinctive patterns were identified: (1) a torpedo-shaped pattern resulting from low R-R interval dispersion over the entire range of heart rates, (2) a fanshaped pattern resulting from restriction of overall R-R interval ranges with enhanced dispersion, and (3) complex patterns with clusters of points characteristic of stepwise changes in R-R intervals. Poincaré pattern could not be predicted from standard deviations of R-R intervals. This first use of Poincaré plots in heart rate variability analysis reveals a complexity not readily perceived from standard deviation information. Further study is warranted to determine if this method will allow refined assessment of cardiac-autonomic integrity in heart failure, which could help identify patients at highest risk for sudden death.

Death, Sudden↗
PubMed1992

Heart rate dynamics after acute cocaine administration.

We examined heart rate (HR) patterns after a bolus intravenous (i.v.) administration of a high (10 mg/kg) dose of cocaine in unrestrained cats. Mean R-R intervals, SD, and other measures of variability were assessed in three periods: waking baseline, early postcocaine administration, and later recovery periods. Cocaine resulted in initial tachycardia and reduced HR variability. This reduction in variability was independent of changes in the average rate: during the recovery period, HR returned to baseline values, but the reduced variability persisted. Nonlinear methods of assessment yielded additional results: Cocaine introduces a high correlation between one beat and the next and a tendency for cardiac accelerations to be followed immediately by decelerations and vice versa. The overall effect of the drug is to restrict deviation from a fixed rate.

Animals↗
PubMed1992

Heart rate variability in congenital central hypoventilation syndrome.

Heart rate variability was assessed in 12 patients with congenital central hypoventilation syndrome (CCHS) and in age- and sex-matched controls using SD of time intervals between R waves (R-R intervals), R-R interval histograms, spectral analysis, and Poincaré plots of sequential R-R intervals over a 24-h period using ambulatory monitoring. Mean heart rates in patients with CCHS were 103.3 +/- 17.7 SD and in controls were 98.8 +/- 21.6 SD (p greater than 0.5, NS). SD analysis of R-R intervals showed similar results in both groups (CCHS 102.2 +/- 36.0 ms versus controls 126.1 +/- 43.3 ms; p greater than 0.1, NS). Spectral analysis revealed that, for similar epochs sampled during quiet sleep and wakefulness, the ratios of low-frequency band to high-frequency band spectral power were increased for 11 of 12 patients with CCHS during sleep, whereas a decrease in these ratios was consistently observed in all controls during comparable sleep states (chi 2 = 20.31; p less than 0.000007). During wakefulness, the ratios of low-frequency band to high-frequency band spectral power were similar in both patients with CCHS and controls. Poincaré plots displayed significantly reduced beat-to-beat changes at slower heart rates in the CCHS patients (chi 2 = 24.0; p less than 0.000001). The scatter of points in CCHS Poincaré plots was easily distinguished from controls. All CCHS patients showed disturbed variability with one or more measures. The changes in moment-to-moment heart rate variability suggest that, in addition to a loss of ventilatory control, CCHS patients exhibit a dysfunction in autonomic nervous system control of the heart.

Adolescent↗
PubMed1992

Dynamic analysis of cardiac R-R intervals in normal infants and in infants who subsequently succumbed to the sudden infant death syndrome.

Infants who subsequently succumb to the sudden infant death syndrome (SIDS) have higher heart rates and reduced heart rate variation compared with other infants. We examined dynamic changes in cardiac interbeat intervals to explore these differences in cardiac control. Recordings of electrocardiographic activity and respiratory movement were acquired from 13 SIDS victims before their deaths. Moment-to-moment changes in R-R intervals during quiet sleep, rapid eye movement sleep, and waking were compared with values of 13 matched control infants. For each sleep-waking state, every R-R interval was plotted against the previous interval (Poincaré plots), and each change in interbeat interval was plotted against the previous change. Dispersion of interbeat intervals at different heart rates was reduced in SIDS victims, resulting in Poincaré plots markedly different from those of controls. The dispersion, sampled at the 10th and 90th percentiles of heart rates, was reduced across all sleep-waking states in SIDS victims. At high heart rates, the difference between groups disappeared after correcting for basal rate; however, the reduced range at low heart rates was independent of basal rate. SIDS victims also showed smaller beat-to-beat changes in heart rate and fewer sustained runs of consistent heart rate changes during waking relative to controls. The differences in cardiac rate dynamics suggest altered autonomic control in infants who succumb to SIDS. We speculate that the autonomic disturbance may lead to cardiac instability or may indicate CNS alterations with the potential to affect other vital functions.

Autonomic Nervous System↗
PubMed1992

The maturation of correlations between cardiac and respiratory measures across sleep states in normal infants.

Coordination of cardiac and respiratory measures is not mature in newborn infants but develops during early life. The course of that development is assessed in this study. Twelve-hour recordings of electrocardiogram, electroencephalogram, digastric electromyogram, electrooculogram and expired CO2 were obtained from 25 normal infants at 1 week and 1, 2, 3, 4 and 6 months of age. Each 1-minute epoch was classified as quiet sleep, rapid eye movement (REM) sleep, waking or indeterminate state. In each sleep-waking state, the correlations of heart rate with respiratory rate, heart rate with respiratory rate variability and respiratory rate with its own variability were determined on a minute-by-minute basis for each recording. The relative extents of correlations between measures and the maturational trends of these correlations were profoundly influenced by sleep-waking state. During quiet sleep, two of the three correlations weakened significantly over the first month of life, but, in the waking state, the same correlations strengthened over this period. During quiet sleep and waking, the three correlations showed similar patterns of development, but the three showed dissimilar developmental trends during REM sleep. These dissimilarities may reflect changes in the nature of REM sleep consequent to myelination of rostral brain pathways.

Arousal↗
PubMed1992

Sleep state organization in normal infants and victims of the sudden infant death syndrome.

Infants at increased risk of the sudden infant death syndrome (SIDS) show abnormal patterning of sleep-waking states. It was hypothesized that infants who were to die of SIDS would show abnormalities of sleep state distribution prior to their deaths. Twenty-two 12-hour recordings were obtained from infants who subsequently died of SIDS, and sleep state patterns were compared in these records and 66 records of age-matched control infants. Each 1-minute epoch was classified as quiet sleep, rapid eye movement (REM) sleep, waking, indeterminate state, or artifact-contaminated. Victims of SIDS showed less waking and more sleep than control infants during the early-morning hours. Victims of SIDS younger than 1 month of age showed significantly more epochs classified as REM sleep across the night and significantly fewer epochs contaminated by artifacts relative to control infants. Further analysis indicated that the increased number of REM epochs resulted from fewer artifact-contaminated epochs, suggesting reduced motility during REM sleep in the SIDS victims compared with the control infants. The finding of decreased waking time during the early morning is of particular importance since most SIDS deaths occur during this portion of the day. The findings of altered sleep patterns in SIDS victims suggest that central neural changes are associated with SIDS risk.

Analysis of Variance↗
PubMed1991

Respiratory-related activity in hypoglossal neurons across sleep-waking states in cats.

Activity of behaviorally identified neurons in the hypoglossal nuclei supplying the genioglossal muscles was assessed in intact, unanesthetized cats across sleep-wake states. Nineteen of 37 recorded cells discharged on a breath-by-breath or tonic basis with the respiratory cycle in at least one state. Most respiratory-related cells discharged more slowly during quiet sleep, whereas rates during rapid eye movement sleep were similar to those of waking.

Animals↗
PubMed1991

Non-linear dynamics of electrocardiographic waveforms following cocaine administration.

We examined dynamics of ECG waveforms preceding and following 10 mg/kg intravenous administration of cocaine in freely moving cats. Cocaine induced substantial variation in ECG waveforms, as demonstrated by non-linear procedures of phase-plane plots and Poincaré analyses. Phase-plane plots revealed that waveform variation following cocaine administration was not randomly or uniformly distributed, but instead followed patterns of clustered organization with unvisited regions. These patterns are characteristic of chaotic distributions, and support the hypothesis that ECG waveform variation following cocaine does not degenerate into random patterns; instead, the variation follows deterministic, though chaotic patterns.

Animals↗
PubMed1991

Dynamic properties of respiratory timing following cocaine administration.

We assessed the timing and amplitude characteristics of diaphragmatic muscle activity following administration of intravenous cocaine HCl (10 mg/kg) to awake, unrestrained cats. Cocaine produced a pronounced tachypnea which was interrupted by deep inspiratory efforts coincident with tonic-clonic movements over the first 10 min following cocaine administration. Following that period, diaphragmatic cycle rates slowly increased for up to 1 h and were interrupted occasionally by longer inspiratory efforts which were not associated with other overt motor activities. As respiratory rate increased, breath-to-breath variability decreased, and the incidence of deep inspiratory efforts decreased. As total cycle time decreased, the ratio of inspiratory time to expiratory time remained the same between precocaine and early, intermediate and late intoxication periods. The amplitude of diaphragmatic EMG activity increased with the extreme tachypnea. A number of neural mechanisms may mediate the changes in diaphragmatic muscle activity, including hyperthermia and alteration of rostral brain influences on brainstem timing mechanisms.

Animals↗
PubMed1991

Upper airway and diaphragmatic muscle activity following acute cocaine administration.

These studies examined activity of the diaphragm and a laryngeal dilator, the posterior cricoarytenoid, following 3 levels of intravenous and cerebral ventricular administration of cocaine. Both administration routes induced extremely high respiratory rates with enhanced tonic and phasic electromyographic activity, and affected patterning similarly in upper airway and diaphragmatic muscles. Both intravenous and intraventricular administration induced a rise in core and brain temperature related to the route of administration; however, the tachypnea was only loosely related to the hyperthermia. Intraventricular administration resulted in a more rapid onset of peak respiratory rates, and a faster decline than an intravenous route. Different dose levels elicited similar elevated respiratory rates, but higher intravenous doses also resulted in extensive hypertonicity with intermittent phasic movements. Tachypnea continued between these phasic efforts. The phasic events associated with high doses were accompanied by sustained inspiratory efforts; however, no evidence of obstructive apnea was found. These data suggest that cocaine can modify respiratory patterning by inducing a centrally mediated tachypnea and by eliciting sustained, intermittent inspiratory efforts.

Animals↗