Fever and chills in an elderly man with a history of blunt trauma.
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Aged↗
Biomedical subjects
R M Harper
Publications and source records attributed to R M Harper.
Identification of human brain regions underlying responses to resistive inspiratory loading with functional magnetic resonance imaging.
Compensatory ventilatory responses to increased inspiratory loading are essential for adequate breathing regulation in a number of pulmonary diseases; however, the human brain sites mediating such responses are unknown. Midsagittal and axial images were acquired in 11 healthy volunteers during unloaded and loaded (30 cmH2O; 1 cmH2O = 98 Pa) inspiratory breathing, by using functional magnetic resonance imaging (fMRI) strategies (1.5-tesla MR; repetition time, 72 msec; echo time, 45 msec; flip angle, 30 degrees; field of view, 26 cm; slice thickness, 5 mm; number of excitations, 1; matrix, 128 x 256). Digital image subtractions and region of interest analyses revealed significantly increased fMRI signal intensity in discrete areas of the ventral and dorsal pons, interpeduncular nucleus, basal forebrain, putamen, and cerebellar regions. Upon load withdrawal, certain regions displayed a rapid fMRI signal off-transient, while in others, a slower fMRI signal decay emerged. Sustained loading elicited slow decreases in fMRI signal across activated regions, while second application of an identical load resulted in smaller signal increases compared to initial signal responses (P < 0.001). A moderate inspiratory load is associated with consistent regional activation of discrete brain locations; certain of these regions have been implicated in mediation of loaded breathing in animal models. We speculate that temporal changes in fMRI signal may indicate respiratory after-discharge and/or habituation phenomena.
Adult↗
Rostral ventral medullary surface activity during hypercapnic challenges in awake and anesthetized goats.
Regions within the rostral ventral medullary surface (RVMS) play an important role in cardiorespiratory responses to CO2 during anesthesia. Activity within a RVMS area, in which local cooling elicited marked ventilatory and blood pressure reductions, was measured as 660 nm scattered light changes in 5 goats following 5% CO2 challenges during waking and anesthetic states. During wakefulness, hypercapnia elicited a substantial, short latency transient (1-1.5 min) activity increase, followed by a sustained decrease. Stimulus cessation elicited a large and rapid off-transient activity increase which persisted for approximately 20 min. In contrast, during halothane anesthesia, the initial activation was absent, and the later activity decline and off-response were much reduced. We conclude that biphasic RVMS activity responses emerge to CO2 stimulation, and are state-dependent.
Administration, Inhalation↗
Ventral medullary surface responses to hypoxic and hyperoxic transient ventilatory challenges in the cat.
Carotid body afferent contributions to activity of the intermediate area of the ventral medullary surface (IVMS) following transient hypoxia and hyperoxia were examined in 6 spontaneously breathing, pentobarbital-anesthetized cats. Two tidal breaths of 100% N2, 100% O2, or room air, were randomly administered before and after carotid sinus denervation (CSD). Images of scattered light from the IVMS showed that activity increased with hypoxia (10.1 +/- 2.4%), and decreased with hyperoxia (4.8 +/- 1.8%). CSD significantly increased the magnitude and delayed the onset of the hypoxic response, but reversed the initial component of the hyperoxic response. We conclude that carotid body afferents modulate the magnitude and timing of IVMS responses to transient respiratory challenges.
Animals↗
State-dependent respiratory and cardiac relationships with neuronal discharge in the bed nucleus of the stria terminalis.
Discharge patterns of 63 neurons in the bed nucleus of the stria terminalis (BNST) were cross-correlated with inspiratory onsets of the respiratory cycle and the R wave of the cardiac cycle in seven unrestrained, drug-free cats during waking (AW), quiet sleep (QS) and rapid eye movement (REM) sleep. BNST neurons fired slowly, with half having rates of less than 1/second; rates were higher in AW and REM states than in QS. Approximately one-quarter of cells showed a phasic discharge timing relationship with the respiratory cycle, and one-fifth with the cardiac cycle, in at least one sleep-waking state. Respiratory-cell correlations occurred more frequently during AW (18 cells) and QS (15) than REM (6), while cardiac-neuronal correlations preferentially developed during QS (13 cells) or REM sleep (11), with a smaller proportion during waking (7). Cardiac-cell discharge correlations were weaker than respiratory-cell correlations and much weaker during REM than during either AW or QS. The data suggest that sleep states modulate a respiratory-dependent neuronal discharge in this rostral site classically associated with affective functions, with the relationship being reduced during REM.
Animals↗
Ventilatory responses to repeated short hypercapnic challenges.
In early phases of respiratory disease, patients are more likely to experience intermittent hypercapnia than a continuous increase in PCO2. The effect of intermittent arterial PCO2 elevation on subsequent breathing patterns is unclear. To examine this issue, a series of six ventilatory challenges (CH1-CH6), consisting of 2 min of breathing 5% CO2 in O2, followed by 5 min in room air (RA) were performed in 10 naive healthy subjects (age 12-39 yr). Minute ventilation (VE) increased from 11.9 +/- 1.0 (SE) l/min in RA to 27.6 +/- 3.0 l/min in 5% CO2 (P < 0.0005) in each of the six hypercapnic challenges. Respiratory rate increased from 21.3 +/- 2.6 breaths/min on RA to 29.6 +/- 3.9 breaths/min during CH1 (P < 0.05). However, respiratory rate consistently decreased with successive CO2 challenges (CH6: 21.5 +/- 2.6 breaths/min; P < 0.02). Thus, maintenance of VE was achieved by gradual increases in tidal volume with each of the first four consecutive CO2 challenges (CH1: 1.05 +/- 0.09 liters; CH4: 1.44 +/- 0.13 liters; P < 0.002). Similarly, the ratio of tidal volume to inspiratory time increased from CH1 (1.16 +/- 0.16 l/s) to CH6 (1.57 +/- 0.21 l/s; P < 0.001). These changes in ventilatory strategy were not observed when RA recovery periods were extended to 15 min in five subjects. We conclude that during repeated short hypercapnic challenges similar levels of VE are achieved. However, increased mean inspiratory flows are generated to maintain VE. We speculate that intermittent hypercapnia either modifies central controller gain or induces a long-term modulatory effect to account for the progressive changes in ventilatory components.
Administration, Inhalation↗
Afferent contributions to intermediate area of the cat ventral medullary surface during mild hypoxia.
The intermediate area of the cat ventral medullary surface activates to mild hypoxia. Carotid body and vagal afferent contributions to this response were examined by recording activity levels, measured as changes in scattered 660 nm light, from the medullary surface in 7 anesthetized, spontaneously breathing cats following 12% O2 in N2 ventilatory challenge. A miniaturized video camera collected images synchronous with the peak of cardiac R wave at 1/s, from a 3.2 mm diameter area, before, and following bilateral carotid sinus denervation (CSD) and vagotomy. In intact animals, hypoxia increased activity; however, greater increases in activity levels followed CSD, while vagotomy elicited a marked reduction of the response. Thus, carotid body afferents exert inhibitory or disfacilitatory influences on intermediate area neurons, while the vagus appears to play an excitatory role.
Afferent Pathways↗
Dynamic magnetic resonance imaging of human Rolandic cortex.
Rolandic cortex was imaged with magnetic resonance (MR) in nine subjects while performing a motor activation task. Imaging was performed by a volumetric, T2-weighted pulse sequence in a conventional 1.5 Tesla scanner during both resting conditions and volitional toe flexion and extension of the dominant foot. Significant changes in MR signal intensity of 7.8 +/- 2.3% (mean +/- s.e.m.) were observed in the medial Rolandic cortex contralateral to the active foot. Changes were maximal in the vicinity of the central sulcus, but were also identified anteroposteriorly, across successive coronal planes. No significant changes were found in the ipsilateral Rolandic cortex or in other brain structures. Volumetric functional MRI strategies may provide an important non-invasive tool for assessment of cortical motor function.
Adolescent↗
Dynamic respiratory responses to preoptic/anterior hypothalamic warming in the sleeping cat.
Timing and amplitude characteristics of diaphragmatic muscle activity following bilateral local warming of the preoptic area/anterior hypothalamic region (POAH) were studied during sleep in free-moving, intact adult cats. Warming of the POAH increased local brain temperature by 1.4-3.7 degrees C and elicited thermal tachypnea (panting) during quiet sleep (QS). Following transition to rapid eye movement (REM) sleep, the tachypnea, initially induced by warming during QS, diminished, but respiratory rates remained above baseline REM levels, and an intermittent pattern of faster and slower breathing rates developed. In QS, tachypnea resulted primarily from a decline in inspiratory time (TI), whereas in REM sleep, reduction in expiratory time (TE) was more prominent. Although diaphragmatic electromyographic amplitude decreased by 40% during panting in QS, the much higher respiratory rates (+350%) resulted in apparent increases in relative ventilation and inspiratory drive. A less pronounced respiratory rate change (+46%) emerged during REM sleep, resulting in no significant changes in ventilation and inspiratory drive in response to warming in that state. The results suggest that descending thermal influences on respiratory patterning differ between QS and REM states in both overall respiratory rate and on relative TI and TE, and thus do not affect inspiratory drive exclusively.
Animals↗
A data acquisition system for long-term monitoring of physiological and video signals.
We developed a system for interleaving digitized physiological signals and video images of subjects onto digital media in a standard file format. The system consists of a framegrabber used to digitize video signals, a microcomputer used to digitize analog signals and send the resulting signals over a parallel interface, and a host laboratory computer to gather and store the video and analog data in an interleaved format as a single file. The system allows for digital storage, search and display of video signals concurrently with physiological signals.
Brain↗
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↗
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↗
The neuropathology of the sudden infant death syndrome. A review.
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Brain↗
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↗
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↗
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↗
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↗
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↗