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Biomedical subjects

R M Harper

Publications and source records attributed to R M Harper.

At least 19 recordsLinked to original sources
PubMed2001

A device for feline head positioning and stabilization during magnetic resonance imaging.

Minimization of head movement and reproduction of standard head positions are essential for reliable brain functional magnetic resonance imaging. Devices for stabilization and alignment of feline preparations are not available currently. We describe a system that involves minimal surgery, allows for both acute and chronic atraumatic positioning, and has the potential to be used for unanesthetized animals. The device uses non-metallic materials and stabilizes the head by means of an apparatus that fixes the head with nylon screws and dental cement in the frontal sinuses. Application of the head-stabilizing device decreases head movements by more than a factor of ten. Anatomical images show that this device provides 3 dimensional head placement at a precision comparable to that of a stereotactic frame, i.e. within 1 mm.

Animals↗
PubMed2001

Autonomic control during sleep and risk for sudden death in infancy.

A variety of clinical pathology and experimental animal evidence suggests that cerebellar and vestibular structures mediate marked challenges to blood pressure and breathing, and are particularly involved in compensatory somatomotor and breathing efforts to overcome substantial losses in blood pressure. At least a subset of victims of the Sudden Infant Death Syndrome (SIDS), a sleep-related disorder, succumbs to a profound bradycardia and hypotension prior to respiratory cessation, suggesting a failure of autonomic control, or incompetent compensation of somatomotor and respiratory efforts, to overcome the cardiovascular collapse. The clinical and neurotransmitter evidence from SIDS victims implicates afferent and efferent components within vestibular/cerebellar blood pressure control systems in SIDS victims. Experimental evidence from animals suggests vestibular and cerebellar structures exercise critical roles in mediating autonomic responses to body position and extreme changes in blood pressure. The position-dependent risk for SIDS, together with the neuropathological evidence, suggests a significant role for vestibular/cerebellar structures in mediating the fatal outcome for the syndrome.

Autonomic Nervous System↗
PubMed2000

Visualization of sleep influences on cerebellar and brainstem cardiac and respiratory control mechanisms.

Cerebellar and vestibular structures exert substantial influences on breathing and cardiovascular activity, particularly under conditions of extreme challenges. Influences from these structures, as well as from the ventral medullary surface, are greatly modified during sleep states. Vestibular lesions abolish the pronounced phasic autonomic variation found in the rapid eye movement sleep state, and spontaneous ventral medullary surface activity, as assessed by optical procedures, is greatly diminished in that state. Neural responses from the ventral medullary surface to hypotensive challenges are enhanced and appear "undampened" during the rapid eye movement sleep state. Functional magnetic resonance imaging reveals activation to blood pressure challenges in widespread brain areas of humans, and especially in cerebellar sites, such as the fastigial nucleus. A subset of victims of sudden infant death syndrome, a sleep-related disorder, appear to succumb from cardiovascular failure of a shock-like nature, and often show neurotransmitter receptor deficiencies in the ventral medullary surface, caudal midline raphe hypotensive regions, and the inferior olive, a major afferent relay to the cerebellum. Afferent and efferent vestibular/cerebellar structures, or sites within the cerebellum may mediate failure mechanisms in sudden infant death syndrome and a number of other sleep-disordered breathing and cardiovascular syndromes.

Animals↗
PubMed2000

Changes in ventral medullary light reflectance during hypercapnia in awake and sleeping cats.

Activity within rostral and intermediate ventral medullary surface areas, measured as 660 nm scattered light changes, was examined in six cats, (five experimental, one control site) following 5% CO(2) challenges during waking, quiet sleep, and rapid eye movement (REM) sleep states. Activity declined to hypercapnia in all states, with a smaller decline in quiet sleep compared to waking, and intermediate values in REM sleep. The decline occurred more rapidly, with a shorter latency, during wakefulness, but with a much slower return to baseline than during quiet sleep. During REM sleep, the latency to nadir and recovery were greater than in other states. Regional patterns of activation emerged which differed in extent of activation between states.

Animals↗
PubMed2000

Lateralized and widespread brain activation during transient blood pressure elevation revealed by magnetic resonance imaging.

The location and possible lateralization of structures mediating autonomic processing are not well-described in the human. Functional magnetic resonance imaging procedures were used to demonstrate signal changes in multiple brain sites during blood pressure challenges. Magnetic resonance signals in brain tissue were visualized with a 1.5 Tesla scanner in 11 healthy volunteers (22-37 years), by using echo-planar procedures. Images were collected during baseline states and three pressor challenges: cold application to the hand or forehead, and a Valsalva maneuver. Image values from experimental conditions were compared with corresponding baseline values on a voxel-by-voxel basis to identify brain regions responsive to physiologic activation. Probability maps (P < 0.01) of voxel changes, with Bonferroni corrections for multiple comparisons, were determined, and amplitude of signal changes associated with significance maps were pseudocolored and overlaid on anatomic images. The time courses and extent of signal alterations in defined unilateral regions were followed and compared with changes in corresponding regions on the contralateral side. Pressor challenges elicited significant regional signal intensity changes within the orbitomedial prefrontal cortex, temporal cortex, amygdala, hippocampal formation, thalamus, and hypothalamus. Cerebellar, midbrain, and pontine areas were also recruited. Signal changes, especially at forebrain sites, were often highly lateralized. The findings indicate that (1) transient, behaviorally-coupled cardiovascular challenges elicit discrete activity changes over multiple brain sites, and (2) these activity changes, especially in specific prefrontal and temporal forebrain regions and cerebellum, are often expressed unilaterally, even to a bilateral challenge.

Adult↗
PubMed2000

Sleep influences on homeostatic functions: implications for sudden infant death syndrome.

The mechanisms underlying the sudden infant death syndrome (SIDS) appear to have origins in the fetal environment resulting in neural damage which later compromises responses to breathing or blood pressure challenges during sleep. The deficits appear to involve alterations in neurotransmitter receptors within regions involved in chemoreception and cardiovascular control. SIDS risk is enhanced by pre- and postnatal nicotine exposure, and possibly by hypoxic experiences. The prone sleeping position plays a significant role in risk, as do head positions that minimize facial escape from enclosed spaces; elevated body temperature may also be a factor. Compensatory mechanisms, including diminished gasping ability, relative failure to arouse to a safer state, or a failure to recruit respiratory efforts to overcome a blood pressure loss have been the object of recent research efforts. The findings suggest that the fatal event involves a neurally-compromised infant, circumstances that challenge vital physiology, most likely during sleep, at a particular developmental period.

Animals↗
PubMed2000

The NPH4 locus encodes the auxin response factor ARF7, a conditional regulator of differential growth in aerial Arabidopsis tissue.

Organ bending through differential growth represents a major mechanism by which plants are able to adaptively alter their morphology in response to local changes in the environment. Two plant hormones, auxin and ethylene, have been implicated as regulators of differential growth responses; however, the mechanisms by which they elicit their effects remain largely unknown. Here, we describe isolation of the NPH4 gene of Arabidopsis, which is conditionally required for differential growth responses of aerial tissues, and we report that NPH4 encodes the auxin-regulated transcriptional activator ARF7. The phenotypes of nph4 mutants, which include multiple differential growth defects associated with reduced auxin responsiveness, including impaired auxin-induced gene expression, are consistent with the predicted loss of function of a transcriptional activator, and these phenotypes indicate that auxin-dependent changes in gene transcription are prerequisite for proper organ bending responses. Although NPH4/ARF7 appears to be a major regulator of differential growth, it is not the sole regulator because phenotypes of nph4 null mutants were suppressed by application of ethylene. This latter finding illustrates the intimate connection between auxin and ethylene in the control of growth in higher plants.

Arabidopsis↗
PubMed2000

Sleep states alter ventral medullary surface responses to blood pressure challenges.

Ventral medullary surface (VMS) activity declines during rapid eye movement (REM) sleep, suggesting a potential for reduced VMS responsiveness to blood pressure challenges during that state. We measured VMS neural activity, assessed as changes in reflected 660-nm wavelength light, during pressor and depressor challenges within sleep/waking states in five adult, unrestrained, unanesthetized cats and in two control cats. Phenylephrine elevated blood pressure and elicited an initial VMS activity decline and a subsequent rise in VMS activity in all states, although the initial decline during quiet sleep occurred only in rostral placements. Phasic REM periods elicited a momentary recovery from the evoked activity rise, and arousals diminished the overall elevation in activity. A sodium nitroprusside depressor challenge increased VMS activity more in REM sleep than in quiet sleep, with the increase being even less in waking. Enhanced responses to depressor challenges during REM sleep suggest a loss of dampening of evoked activity during that state; state-related differential baroreflex sensitivity may result from sleep-waking changes in VMS responses to blood pressure challenges.

Adrenergic alpha-Agonists↗
PubMed2000

State influences on ventral medullary surface and physiological responses to sodium cyanide challenges.

Intravenous sodium cyanide (NaCN) administration lowers ventral medullary surface (VMS) activity in anesthetized cats. Sleep states modify spontaneous and blood pressure-evoked VMS activity and may alter VMS responses to chemoreceptor input. We studied VMS activation during peripheral chemoreceptor stimulation by intravenous NaCN using optical procedures in six cats instrumented for recording sleep physiology during sham saline and control site trials. Images of scattered 660-nm light were collected at 50 frames/s with an optical device after 80-100 microg total bolus intravenous NaCN delivery during waking and sleep states. Cyanide elicited an initial ventilatory decline, followed by large inspiratory efforts and an increase in respiratory rate, except in rapid eye movement sleep, in which an initial breathing increase occurred. NaCN evoked a pronounced decrease in VMS activity in all states; control sites and sham injections showed little effect. The activity decline was faster in rapid eye movement sleep, and the activity nadir occurred later in waking. Sleep states alter the time course but not the extent of decline in VMS activity.

Animals↗
PubMed2000

Sudden infant death syndrome: a failure of compensatory cerebellar mechanisms?

The mechanisms underlying failure in sudden infant death syndrome may involve inadequate compensatory motor responses to a hypotensive challenge; the insult may result from a shock-like sequence, or from a ventilatory challenge that leads to a hypotensive event. Structures ordinarily not considered in mediating breathing or cardiovascular control, especially cerebellar-related structures, may play a critical role in compensatory responses, and underlie the position-dependent risk for SIDS. Dysfunction in affected brain areas appears to arise prenatally from a compromised fetal environment, with a nicotinic component contributing to the deficient mechanism. Physiologic characteristics of infants who later succumb to SIDS, and cardiovascular events associated with the fatal scenario suggest a failure of interaction between somatomotor and autonomic control mechanisms in infants at risk for the syndrome. A failure of compensatory motor actions to overcome a profound hypotension, perhaps mediated by cerebellar mechanisms that regulate blood pressure, may underlie-the fatal event.

Cerebellum↗
PubMed1999

Acquisition of electrophysiologic signals during magnetic resonance imaging.

We describe a low cost system for acquiring electrophysiological signals during magnetic resonance imaging. The system consists of high common-mode-rejection and low noise operational amplifiers, coupled by fiber optic cables to a receiver located at the periphery of the magnetic field. The system minimizes noise introduction which would contaminate image signals.

Electrophysiology↗
PubMed1999

Physiological and ventral medullary surface activity during hypovolemia.

The objective was to determine ventral medullary surface responses to blood loss sufficient to induce shock. We examined changes in scattered light from rostral and intermediate areas of the ventral medullary surface in four intact, drug-free cats during acute hypovolemia. Scattered light images, collected during 660 and 560 nm illumination to measure cellular activity and hemodynamic aspects, respectively, were digitized at 50 frames/s during baseline, and during withdrawal of 20-30% blood volume. Hypovolemia elicited a profound hypotension and eventual bradycardia. In all cats, a modest increase in ventral medullary surface reflectance (activity decline) accompanied initial blood loss; as hypovolemia continued, and blood pressure declined, reflectance switched to a decline (activity increase), with the lowest reflectance occurring at maximal blood loss. Hypovolemia elicited multiple transient physiologic behaviors, including tachycardia, tachypnea, intermittent isolated and sustained bursts of enhanced inspiratory efforts, and extensor activation of the somatic musculature. The phasic physiological behaviors during hypovolemia were accompanied by partial recovery of medullary surface reflectance and blood pressure towards baseline values; however, reflectance continued to decrease as blood pressure progressively fell after these recovery efforts. Patterns of reflectance were not uniform over areas examined; isolated regions of enhanced or diminished reflectance appeared upon the overall images. Optical signals indicating hemodynamic changes followed the neural activity patterns, but not precisely. Regions within the ventral surface are responsive to hypovolemia, and to transient behaviors associated with momentary restoration of blood pressure; these ventral surface areas may assume essential roles in the systemic response to hypovolemic-induced shock.

Animals↗
PubMed1999

Novel insights into congenital hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) is a rare and unique condition that may prompt unparalleled approaches to the discovery of genes involved in development of cardiorespiratory control and gas exchange homeostasis. Its higher risk of recurrence in families and its association with Hirschsprung's disease suggest that an underlying genetic mechanism is involved. However, screening for mutations of the receptor tyrosine kinase RET and endothelin 3 has revealed only occasional patients affected by these mutations, therefore suggesting that CCHS may result from disruption of more than a single gene. In recent years, three principal issues have become apparent: 1) the autonomic nervous system is involved universally in CCHS cases, albeit to a varying extent; 2) the use of novel functional imaging approaches incorporating refined stimulus paradigms may provide essential research and clinical insights into localization and assessment of neural sites underlying the phenotypic expression of this syndrome; and 3) efforts to transition patients' nocturnal respiratory support to a noninvasive ventilatory modality should be critically evaluated and pursued, when appropriate, to improve the quality of life for patients and families.

Autonomic Nervous System↗
PubMed1999

Optical imaging of the ventral medullary surface across sleep-wake states.

We hypothesized that spontaneous activity declines over widespread areas of the cat ventral medullary surface (VMS) during rapid eye movement (REM) sleep. We assessed neural and hemodynamic activity, measured as changes in reflected 660- and 560-nm wavelength light, from the VMS during sleep and waking states in five adult, unrestrained cats and in two control cats. Relative to quiet sleep, overall activity declined, and variability, assessed by standard deviation, increased by 25% during REM sleep. Variability in activity during waking also increased by 45% over quiet sleep, but mean activity was unchanged. REM sleep onset was preceded by a reduction in the hemodynamic signal from 5 to 60 s before neural activity decline. The activity decline during REM sleep, previously noted in the goat rostral VMS, extends to intermediate VMS areas of the cat and differs from most neural sites, such as the cortex, hippocampus, and thalamus, which increase activity during REM sleep. The activity decline during REM sleep has the potential to modify VMS responsiveness to baroreceptor and chemoreceptor challenges during the REM state.

Animals↗
PubMed1998

Developmental patterns of heart rate and variability in infants with persistent apnea of infancy.

During periods of regular breathing, heart rate is slower and more variable in healthy (no history of respiratory distress syndrome) prematurely born infants with persistent apnea, relative to full-term control infants of comparable post-conceptional ages. We tested the hypothesis that the cardiovascular differences may be linked to the persistent apnea, rather than premature birth, by assessing heart rate and variability in full-term infants with persistent apnea. Thus, resting heart rate and variability were compared in full-term infants with apnea of infancy, prematurely born infants with persistent apnea, and full-term control infants. Full-term infants with persisting apnea showed slower heart rates than control infants, beginning at 4 months after birth, and enhanced heart rate variability beginning at 6 months. Healthy prematurely born infants with persistent apnea showed cardiovascular alterations similar to those of full-term infants with apnea; these alterations differed from those observed in very premature infants with histories of respiratory distress. The postnatal development of cardiovascular aberrations in infants with persistent apnea suggests that mechanisms accompanying apneic events may contribute to long-term alterations in autonomic control.

Aging↗
PubMed1998

Relationships between hippocampal activity and breathing patterns.

Single cell discharge, EEG activity, and optical changes accompanying alterations in breathing patterns, as well as the knowledge that respiratory musculature is heavily involved in movement and other behavioral acts, implicate hippocampal regions in some aspects of breathing control. The control is unlikely to reside in oscillatory breathing movements, because such patterns emerge in preparations retaining only the medulla (and perhaps only the spinal cord). However, momentary changes in breathing patterns induced by affect, startle, whole-body movement changes, or compensatory ventilatory changes mediated by rostral brain regions likely depend on hippocampal action in aspects of control. Hippocampal activity was enhanced prior to sighs, and this enhancement was accompanied by increased slow theta activity. Theta frequency increased during apnea, prior to return of breathing. Consideration of hippocampal contributions to breathing control should be viewed in the context that significant interactions exist between blood pressure changes and ventilation, and that modest breathing challenges, such as exposure to hypercapnia or to increased resistive loads, bring into action a vast array of brain regions involving nearly every level of the neuraxis.

Animals↗