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Biomedical subjects

R M Harper

Publications and source records attributed to R M Harper.

At least 73 records · Page 4Linked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Pressor-induced responses of the cat ventral medullary surface.

We examined ventral medullary surface activity using light reflectance procedures after blood pressure alterations induced by phenylephrine or sodium nitroprusside in 23 pentobarbital sodium-anesthetized cats. Images of reflected 660-nm light were collected and digitized at 1- to 3-s intervals after baseline and intravenous saline, 5-40 micrograms/kg phenylephrine, or sodium nitroprusside infusion. Carotid sinus nerve denervation (CSD) and bilateral vagotomy were performed in five and three animals, respectively, and challenges were repeated. Phenylephrine elicited a dose-dependent transient blood pressure elevation and reflectance increase (interpreted as activity decline) over the entire ventral medullary surface examined. The increase consisted of an initial rapid transient component, peaking at 45 s, and a 3- to 5-min recovery. CSD enhanced, and vagotomy substantially reduced, the initial transient response to phenylephrine. Sodium nitroprusside-induced lowering of blood pressure was associated with decreased reflectance in rostral sites and increased reflectance in caudal regions. CSD abolished a late component and diminished amplitude of an initial rapidly rising component of changes induced by nitroprusside, a decline further accentuated by addition of vagotomy.

Animals↗
PubMed1995

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↗
PubMed1995

Ventilatory response to consecutive short hypercapnic challenges in children with obstructive sleep apnea.

In healthy adults, a ventilatory pattern characterized by progressively increased tidal volume (VT), and decreased respiratory rate (RR) accompany repeated short hypercapnic ventilatory challenges, while minute ventilation (VE) remains constant. We hypothesized that the peculiar ventilatory pattern seen in adults would be blunted in children with obstructive sleep apnea syndrome (OSAS) who undergo comparable intermittent or chronic alveolar PCO2 elevation. We measured ventilatory responses to five challenges of 2-min duration (C1-C5) with 5% CO2 in O2, separated by 5-min room-air breathing intervals (R1-R4), in nine children with OSAS and in eight age-, sex-, and body mass index-matched controls. In all children, CO2 significantly increased VE when compared with baseline conditions (22.3 +/- 2.2 vs. 9.5 +/- 0.9 (SE) l/min; P < 0.001). In control subjects, progressive VT increases from 0.67 +/- 0.10 liter in C1 to 0.92 +/- 0.13 liter in C5 occurred (P < 0.01), whereas RR decreased from 33.9 +/- 5.1 breaths/min in C1 to 27.8 +/- 3.7 breaths/min in C5 (P < 0.02), resulting in VE increases across CO2 challenges (22.3 +/- 4.9 l/min in C1 vs. 25.1 +/- 5.0 l/min in C5; P < 0.005). The RR decrease was primarily related to progressive prolongation of expiratory time (TE) (1.1 +/- 0.1 s in C1 to 1.5 +/- 0.2 s in C5; P < 0.002). In contrast, VT, RR, and TE did not change in a consistent fashion in OSAS patients with repeated CO2 challenges (OSAS vs. control: P < 0.0001). Furthermore, in OSAS, VE was similar with repeated challenges (22.4 +/- 2.2 1/min in C1 vs. 23.9 +/- 1.9 l/min; P = not significant), such that changes in VE over time significantly differed in OSAS and controls (P < 0.001). We conclude that healthy children modify their ventilatory strategy to repeated hypercapnia. We speculate that in OSAS these mechanisms are already fully implemented because of recurrent alveolar hypoventilation accompanying increased upper airway resistance, leading to blunted temporal trends of ventilatory response.

Adolescent↗
PubMed1995

Maturation of kitten ventral medullary surface activity during pressor challenges.

We used large-array optical recording procedures to examine maturation of regional neural activity within the ventral medullary surface (VMS) of anesthetized kittens during pharmacologically induced blood pressure elevation. Under sodium pentobarbital anesthesia, the VMS was exposed in 10, 20 and 30- to 45-day-old kittens and in adult cats. Arterial pressure, costal diaphragmatic EMG, and ECG were continuously monitored. An imaging camera, composed of a charge-coupled device and a coherent bundle of optic fibers, was positioned over the VMS. Light at 660 nm illuminated the neural tissue, and was collected by the probe. Resulting light-scatter images were acquired at 2-second intervals during a baseline period, and following intravenous administration of phenylephrine at 10, 20 and 40 micrograms/kg. Sixty to seventy-five images within each epoch were averaged, and subtracted from baseline. Regional differences within the image were determined by ANOVA procedures (alpha = 0.05). Phenylephrine elicited dose-dependent elevations of blood pressure accompanied by decreased diaphragmatic EMG activity which were less profound in younger animals. With maturation, responsiveness of respiratory patterning to the pressor response increased. In contrast to adult cats, 10-day kittens increased VMS neural activity in a dose-dependent fashion with pressor stimulation. A progressive transition to adult response patterns was observed with increasing postnatal age, and was established in over half of the kittens by 30-45 days. We conclude that phenylephrine-induced baroreceptor stimulation elicits divergent VMS activity responses in developing and mature animals. Such a developmental pattern may reflect immature function of central and/or peripheral baroreflexes.

Aging↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Low-cost acquisition of video images simultaneously with 240 electrophysiological signals.

We developed a low-cost system for simultaneous collection and storage of physiological and video signals. The system samples and multiplexes up to 240 low-bandwidth analog channels with a camera video signal, and outputs a standard composite video signal containing analog and video data. The combined signals can be stored on video tape or can be digitized by an inexpensive framegrabber. The circuitry separates horizontal synchronizing pulses from a camera output; the pulses increment a counter that sequentially selects each electrophysiological channel on a sample-and-hold multiplexer. The intensity of each horizontal scan line from the multiplexer output represents the amplitude of one sample of each physiological channel. This signal is then multiplexed with the video signal, such that a portion of each video horizontal line represents the physiological data. The combined output is stored together, providing a means for synchronizing the two signals during analysis. The design allows easy coordination of electrophysiological events with video images from a standard video camera, avoiding the necessity for separate analog to digital circuitry for physiological and video signal storage on computer media, as well as the need for complex synchronization of the data from different media.

Costs and Cost Analysis↗
PubMed1994

Distribution of slow-wave EEG activity across the night in developing infants.

Adults show distinctive patterns of slow-wave (delta) electroencephalogram (EEG) activity across each sleep cycle and across the night. We examined the ontogeny of slow-wave EEG patterning in infants. Twelve-hour overnight physiological recordings were obtained from 25 normal infants at 1 week and 1, 2, 3, 4 and 6 months of age. The EEG activity was band-pass filtered, leaving primarily activity ranging from 0.5 to 2.5 Hz (the delta frequency). Filtered EEG traces were full-wave rectified and integrated over 1-minute periods. Nighttime recordings were divided into four 3-hour segments, beginning at sleep onset, and the mean integrated delta activity during quiet sleep was determined for each segment of the night. In addition, patterns of delta activity across extended periods of quiet sleep (15 minutes or longer) were determined. Beginning at 2 months of age, integrated delta activity declined significantly over the night. Moreover, beginning at 3 months of age, delta activity increased significantly over individual periods of quiet sleep; in neonates up to 1 month of age, delta activity decreased significantly within epochs of quiet sleep. Beginning at 2-3 months of age, infants show patterns of delta activity similar to those found in adults.

Cerebral Cortex↗
PubMed1994

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↗
PubMed1994

Ventral medullary surface activity during sleep, waking, and anesthetic states in the goat.

We examined activity, measured as changes in reflected light, from the surface of a rostral ventral medullary area that is involved in cardiorespiratory control. We collected images during sleep and waking states and during halothane anesthesia in five adult unrestrained goats. During quiet sleep, overall activity increased and overall variability decreased compared with waking levels, whereas rapid eye movement sleep increased variability, and average activity decreased to near-waking levels. Distinct regions of activation and suppression appeared during sleep states. Deep anesthesia decreased activity and minimized variation. We speculate that alterations in rostral ventral medullary surface activity may play a role in state-dependent changes in cardiorespiratory control mechanisms.

Activity Cycles↗
PubMed1994

Localization of putative neural respiratory regions in the human by functional magnetic resonance imaging.

In humans, the location of brain regions responsible for mediating the ventilatory response to CO2 remains unknown. Most of the available knowledge has been derived from animal studies or from pathophysiological correlations in patients presenting altered control of breathing. Magnetic resonance imaging at a specific pulse sequence designed to assess changes in brain tissue microcirculation was performed in 11 healthy volunteers, during steady-state conditions, while breathing 100% O2 or 5% CO2-95% O2. In one subject, 10% CO2-90% O2 was employed to examine a dose-response effect. Significant changes in image signal intensity consistently occurred in ventral and dorsal regions of medullary structures as well as in the midline pons and ventral cerebellum. These responses appeared to be dose dependent and reproducible. Magnetic resonance imaging revealed patterns of activation in brain stem and cerebellar regions during hypercapnic ventilatory challenge. These areas may underlie mechanisms for mediating the response to chemoreceptor activation.

Adolescent↗
PubMed1994

Hippocampal reflected optical patterns during sleep and waking states in the freely behaving cat.

We examined reflected light as a measure of neural activity from a 2 mm2 area of dorsal hippocampus and surrounding neocortex in nine freely behaving cats during sleep and waking states. Light reflectance at 660 or 700 nm was measured by a coherent fiber optic probe attached to a charge-coupled device video camera that allowed acquisition of images from subcortical structures. In the dorsal hippocampus, rapid eye movement sleep (REMS) and active waking (AW) resulted in a significant decline (-0.9% +/- 0.3 and -2.0% +/- 0.5, respectively) in overall reflected light from the dorsal hippocampus relative to quiet sleep (QS), while quiet waking (QW) resulted in an overall increase (+2.0% +/- 0.4). In the neocortical probe placement group, reflectance also decreased during AW (-1.6% +/- 0.5) and increased during QW (+1.7 +/- 0.6) as compared to QS. In contrast to the hippocampus, however, overall reflectance increased, rather than decreased, in the neocortex during REMS (+2.7% +/- 1.3). We interpret a decline in reflectance as representing increased activation of underlying neural tissue. Thus, the cat dorsal hippocampus increased overall activity during REMS as compared to QS, while neocortical structures decreased overall activity during the same state. These results concur with expected activity changes based on electrophysiologic and autoradiographic studies. The imaging procedure provided a continuous assessment of spatially organized neural activity changes in the freely behaving animal.

Animals↗
PubMed1993

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↗
PubMed1993

Respiratory patterning following cerebral ventricular administration of cocaine.

Intravenous (IV) cocaine in the conscious cat causes extreme tachypnea and reduction in breath-to-breath variability. In this study, we examined respiratory patterning following administration of cocaine into the cerebral ventricles. Intraventricular cocaine elicited a tachypnea that was nearly identical to that for IV cocaine. At the high dose, peak respiratory rate increased by 380%. Breath-to-breath variability was dramatically reduced by cocaine, especially in the early stages of the intoxication; during these stages, the tachypnea was occasionally interrupted by prolonged inspiratory efforts. Procaine was administered as a control for the anesthetic effects of cocaine and caused an initial tachypnea that was similar to that for cocaine. For both cocaine and procaine, the mean ratios of inspiratory to expiratory durations were unaffected, indicating that the tachypnea was accomplished by approximately equal reductions in inspiratory and expiratory durations. We conclude that the tachypnea following cocaine administration results principally from central rather than peripheral mechanisms. In addition, the data suggest that anesthetic actions mediate the principal respiratory effects of cocaine.

Animals↗
PubMed1993

Imaging of hippocampal and neocortical neural activity following intravenous cocaine administration in freely behaving cats.

We examined spatial-temporal patterns of neural activity, as inferred from 700 nm light reflectance, from the dorsal hippocampus and surrounding neocortex in seven freely behaving cats following 1.5, 2.5, 3.5 and 5.0 mg/kg intravenous cocaine administration. Images were acquired using a new technique which gathered reflected light from cortical and subcortical structures. Cardiac and respiratory patterning, collected simultaneously with optical images, revealed increased rates and diminished variation after intravenous cocaine administration. Cocaine increased reflectance correlates of hippocampal neural activity in a dose-dependent fashion over a 120 min period, with a lengthening time-to-peak effect (22-76 min). The largest dose resulted in an initial decrease, followed by the greatest enhancement in neuronal activity. Correlates of neural activation in the neocortex displayed an inverse dose-response curve to that found in the hippocampus; the time-to-peak effect was shorter (6-43 min) and the maximal change was reduced. Regional patches and bands of activation occurred during the period of the cocaine response, and were more pronounced in the hippocampus than the neocortex. Procaine, administered in a similar dose, slightly increased neural activity for 10 min in both the hippocampus and neocortex, and elicited a small increase in respiration. Cocaine induces a pronounced enhancement of neural activation in the neocortex and dorsal hippocampus; the time course of activation in the hippocampus parallels an increased respiratory pattern and outlasts the neocortical response. We speculate that hippocampal activation may be related to the profound respiratory acceleration found in response to cocaine.

Animals↗