Biomedical subjects

R A Darnall

Publications and source records attributed to R A Darnall.

At least 19 recordsLinked to original sources

PubMed2001

Spontaneous arousals during quiet sleep in piglets: a visual and wavelet-based analysis.

STUDY OBJECTIVES: The objectives of the study were to characterize spontaneous arousals during NREM sleep in piglets and to compare two methods of identifying these events: a "visual" technique using spectral analysis and an automated technique using wavelets. Our goal was to understand the benefits and limits of these methods when applied to sleep in human infants. DESIGN: Arousals were identified by evaluating rapid changes in EEG low frequency activity, blood pressure (BP), and heart rate (HR). A cortical arousal was defined as a rapid decrease in EEG low frequency activity. An autonomic arousal was defined by a transient increase in heart rate or a transient change in mean arterial BP (MAP). SETTING: Laboratory study in sleeping and awake piglets. PARTICIPANTS: Five 1-2 week old piglets. INTERVENTIONS: Chronically instrumented with a femoral arterial line, EEG, EOG, EMG electrodes, and a micro-dialysis probe with its tip located in the rostral ventral medulla. Artificial CSF (aCSF) was dialyzed into the RVM throughout the experiments Measurements: For the visual analysis, the average delta power (0.5-4 Hz) for each 5-second epoch was determined using spectral analysis. MAP and HR were analyzed in 1-second bins. Video images were analyzed for body movements and eye openings. Transient changes in blood pressure, HR, and delta power were then visually identified. For the wavelet analysis, a quantitative, automated technique with a defined "wakefulness threshold" was used to identify rapid decreases in EEG low frequency activity and the rate of change of MAP. RESULTS: Using the visual method, 117 episodes associated with stereotypical hemodynamic, EEG, and behavioral changes (startle) were identified. Seventy five events occurred in isolation or were first in a series of "multiple" events, 41 "multiple" events were defined as events occurring <20 seconds following a previous event. Eighteen events were associated with the termination of apnea. In isolated events or those occurring first in a series, the onset of changes in HR and BP clearly preceded the decrease in EEG amplitude and delta power. Using wavelet analysis, 73 EEG arousals and 115 MAP transients were identified independently; 62% of the EEG events were associated with a transient change in MAP and HR, and in these cases the onset of the hemodynamic events preceded EEG arousals. EEG arousals and MAP transients, however, also occurred alone and not associated with a stereotypical pattern of a startle, changes in MAP and HR and the EEG. CONCLUSIONS: Many of these spontaneous arousals represent integrated EEG, hemodynamic, and behavioral processes similar to arousal phenomena described in adult rats and human infants, but the pattern of spontaneous arousals appears to be more heterogeneous than has been described for arousals induced by exogenous stimuli. Both the visual and wavelet analysis identified these events, but the wavelet technique has the potential advantage of better time resolution and automation of the analysis.

Animals↗

PubMed2001

The effects of a GABA(A) agonist in the rostral ventral medulla on sleep and breathing in newborn piglets.

STUDY OBJECTIVES: Abnormalities in the rostral ventral medulla (RVM) in human infants may contribute to the etiology of the sudden infant death syndrome (SIDS) or a subset of SIDS, by interfering with cardiorespiratory and arousal responses to physiological stimuli often encountered during sleep. The purpose of this study was to determine whether inhibition of groups of neurons in the RVM in newborn piglets would alter sleep and/or the sleep-modulation of breathing. We hypothesized that inhibition of neurons in the RVM would produce less wakefulness or increase the low frequency power (delta) during Quiet sleep. DESIGN: Unanesthetized piglets were studied in a whole-body plethysmograph. Artificial cerebral spinal fluid (aCSF) or the GABAA agonist, muscimol, was dialyzed into the RVM for 40 minutes after a control period consisting of aCSF dialysis. Sleep was analyzed using a combination of EEG spectral analysis and behavioral observations. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Cardiorespiratory variables varied with state. Dialysis of neither aCSF nor muscimol into the RVM resulted in alterations in resting respiration, BP, HR, or VO2 or their modulation by state. Compared to control dialysis with aCSF, muscimol dialysis caused dramatic effects on sleep architecture. Sleep cycling was abolished in some experiments, whereas in others there were decreases in low-frequency EEG activity or delta power. The animals in which sleep cycling ceased continued in a perpetual state of drowsiness interspersed with periods of wakefulness. CONCLUSIONS: We conclude that dialysis of muscimol into the RVM has little effect on resting breathing, blood pressure, or heart rate or their modulation by state, but interferes with normal sleep architecture. We speculate that abnormalities in the ventral medulla may alter sleep cycling or interfere with arousal mechanisms, thus contributing to the etiology of at least a subset of SIDS.

Animals↗

PubMed2001

Muscimol dialysis in the rostral ventral medulla reduced the CO(2) response in awake and sleeping piglets.

Some victims of sudden infant death syndrome have arcuate nucleus abnormalities. The arcuate nucleus may be homologous with ventral medullary structures in the cat known to be involved in the control of breathing and the response to systemic hypercapnia. We refer to putative arcuate homologues in the piglet collectively as the rostral ventral medulla (RVM). We inhibited the RVM in awake and sleeping, chronically instrumented piglets by microdialysis of the GABA(A) receptor agonist muscimol. Muscimol dialysis (10 and 40 mM) had no effect on eupnea but caused a significant reduction in the response to hypercapnia during both wakefulness (34.8 +/- 8.7 and 30.7 +/- 10.1%, respectively) and sleep (36.7 +/- 6.7 and 49.5 +/- 8.9%, respectively). The effect of muscimol on the CO(2) response was entirely via a reduction in tidal volume and appeared to be greater during non-rapid-eye-movement sleep. We conclude that the piglet RVM contains neurons of importance in the response to systemic CO(2) during both wakefulness and non-rapid-eye-movement sleep. We hypothesize that dysfunction of homologous regions in the human infant could lead to impaired ability to respond to hypercapnia, particularly during sleep, which could potentially be involved in the pathogenesis of sudden infant death syndrome.

Aging↗

PubMed2000

Lesion or muscimol in the rostral ventral medulla reduces ventilatory output and the CO(2) response in decerebrate piglets.

Developmental abnormalities have been described in the arcuate nucleus of sudden infant death syndrome (SIDS) victims. The arcuate nucleus has putative homologues in chemosensitive areas of the ventral medulla in animals. We refer to some of these areas collectively as the rostral ventral medulla (RVM). In the RVM of decerebrate piglets 2-15 days of age, we studied the effects of electrolytic lesions (n=7) or microdialysis of muscimol (n=15), a GABAA receptor agonist, on ventilatory output and the response to hypercapnia. Lesions caused a 66.7+/-17.3% reduction in eupneic phrenic minute activity (MA) and abolished the response to hypercapnia. Muscimol dialysis caused a 32.4+/-10.4% reduction in MA with a significant downward displacement of the response to hypercapnia with no significant effect on the slope. We conclude that the piglet RVM contains neurons of vital importance in the maintenance of normal breathing and the response to systemic CO(2). We hypothesize that dysfunction of homologous regions in the human infant could lead to impaired ability to respond to hypercapnia and could potentially be involved in the pathogenesis of SIDS.

Animals↗

PubMed2000

Teaching residents in the neonatal intensive care unit: a non-traditional approach.

Because of the increasing constraints on the amount of time pediatric residents may train in the neonatal intensive care unit (NICU), concerns have been raised about the adequacy of their exposure to acute emergencies in the delivery room and their hands-on experience with sick neonates. Importantly, there are also concerns about the consistency and quality of supervision of PL-1 residents by second- and third-year residents, who themselves may not have had sufficient training in the NICU. To address these concerns, we have instituted an educational plan that links an experienced neonatal nurse practitioner (NNP) one-on-one with a PL-1 resident in a collaborative team. This plan differs from the traditional resident-to-resident supervisory model. An anonymous survey of our residents (n = 14) indicates enthusiastic endorsement of this new educational model. NNPs as first-line teachers in the NICU provide a new approach for residency training programs.

Adult↗

PubMed1999

Modulation of hypoxic depressions of ventilatory activity in the newborn piglet by mesencephalic mechanisms.

In neonates, ventilatory responses to hypoxia are 'biphasic,' with an augmentation followed by a decline. The hypoxia-induced augmentations in ventilation are attenuated and the depressions are accentuated following denervation of the peripheral chemoreceptors. Piglets that were decerebrated at a rostral mesencephalic level exhibited these hypoxia-induced depressions. These depressions were lessened following transection through the caudal mesencephalon. Mesencephalic mechanisms play a fundamental role in the brainstem regulation of ventilatory responses to hypoxia.

Animals↗

PubMed1999

The New Hampshire Perinatal Program: twenty years of perinatal outreach education.

OBJECTIVE: To describe 20 years of regional outreach education by the New Hampshire Perinatal Program, its interaction with all 26 community hospitals in the state with maternity services and an additional four in adjoining Vermont. STUDY DESIGN: This paper describes educational initiatives responsive to the needs of perinatal physicians and nurses. The core of the program is the transport conference held annually at each referring hospital in which maternal-fetal and infant referrals are discussed. There are additional community hospital-based programs, programs at convenient locations in the region and medical center conferences and skills programs. RESULTS: The program annually awards 10,000 continuing medical education credits (CME) and nursing contact hours. Evaluation and feedback from all participants is encouraged. New Hampshire has one of the lowest perinatal mortality rates in the county, which reflects in part the accomplishments of the program. CONCLUSION: Perinatal outreach education is a shared responsibility of providers in both the academic center and community hospitals and is necessary to ensure optimal care for mothers and infants.

Community-Institutional Relations↗

PubMed1997

Margin of safety for discharge after apnea in preterm infants.

OBJECTIVE: Most neonatologists include an apnea-free period in the criteria for the discharge of preterm infants. However, the length of time one should wait after the cessation of apnea before sending an infant home without a monitor is debated. We undertook this study in an attempt to define a minimal and safe observation period between the time of the last apnea episode and discharge. METHODS: We reasoned that in infants with idiopathic apnea of prematurity, the intervals between days on which apnea occurs gradually increase until some point at which clinically significant apnea ceases. Therefore, knowledge about the intervals between days on which apnea occurred just before the last apnea would provide a reasonable estimate of the minimal safe observation interval between the last apnea and discharge. We reviewed the charts of 266 infants born in 1993 and 1994 at </=32 weeks' gestational age or weighing </=1500 g at birth from two institutions to determine the intervals between the day on which the last apnea occurred and the previous two days on which apnea occurred. One hundred seventy-five infants were excluded because they never experienced apnea, or data about the last apnea was missing, or they were on xanthines during the period encompassing the last 3 apnea days, or they weighed <1500 g or were <34 weeks' postmenstrual age at the time of the last apnea. Of the 91 remaining infants, gestational age at birth, birth weight, 1- and 5-minute Apgar scores, and discharge weight were not different between the two institutions. For each infant we determined the longest of the intervals between the 2 days on which apnea occurred previous to the day of the last apnea (MAXINT for maximum interval). The infants were then ordered by MAXINT and, starting at the longest MAXINT, the medical records of each infant were carefully examined for other conditions known to be associated with apnea (eg, recovering from anesthesia, sepsis, chronic lung disease, and so forth). The minimal safe observation period was then defined as the longest MAXINT in which there was at least 1 infant with no other explanation for the apnea other than prematurity. RESULTS: The median duration of the intervals between the 2 days on which apnea occurred previous to the day on which the last apnea occurred were 3. 0 and 2.0 days and the median duration of the MAXINT was 4.0 days. On careful examination of the charts, it was determined that each of 13 infants with a MAXINT preceding the day on which the last apnea occurred of greater than 8 days had some other condition that might result in apnea, including residual lung disease, sepsis, surgery, and so forth. In contrast, among the group of infants with a MAXINT of </=8 days, at least 1 infant at each MAXINT (eg, 1 to 8) had significant apnea with no other explanation other than prematurity. CONCLUSIONS: We conclude that otherwise healthy preterm infants continue to have apneas separated by as many as 8 days before the last apnea before discharge. Conversely, infants with longer apnea intervals often have identifiable risk factors other than apnea of prematurity.

Apnea↗

PubMed1996

Characterizations and comparisons of eupnoea and gasping in neonatal rats.

1. Our purpose was to characterize the ventilatory patterns of eupnoea and gasping in the neonatal rat. This study was precipitated by reports, using in vitro brainstem spinal cord preparations, that only a single pattern is present in neonatal rats. 2. In anaesthetized or decerebrate rat pups aged less than 13 days, eupnoea was characterized by a sudden onset of inspiratory activity and then a more gradual rise to peak levels. Following vagotomy, frequency fell and peak phrenic activity and tidal volume increased. The rate of rise of inspiratory activity also rose, but peak levels were still achieved during the latter half of inspiration. Vagal efferent activity exhibited bursts during both inspiration and the early expiration. This basic eupnoeic rhythm was not altered after sectioning of the carotid sinus nerves. 3. Upon exposure to hypoxia or anoxia, phrenic activity, tidal volume and frequency initially increased and then declined. In many animals, ventilatory activity then ceased, but later returned with a gasping pattern. 4. Gasping was characterized by a sudden onset of phrenic activity, which reached a peak intensity during the early portion of inspiration. The expiratory burst of vagal activity was eliminated. 5. Reductions of body temperature from 37 to 27 degrees C resulted in prolongations of inspiration and expiration and decreases of phrenic amplitude; phasic phrenic activity completely disappeared in some animals. Upon exposure to anoxia, gasping was observed, even in animals in which phrenic activity had disappeared in hyperoxia. 6. We conclude that, from the day of birth, rats can exhibit eupnoea and gasping patterns which are very similar to those of adult animals. 7. The rhythmic neural activities of the in vitro brainstem-spinal cord preparation, reported by others, differ markedly from eupnoea but are identical with gasping. We therefore conclude that this preparation is not suitable for investigation of the mechanisms that generate eupnoeic breathing.

Age Factors↗

PubMed1996

Characterization of ventilatory responses to hypoxia in neonatal rats.

Newborn animals exhibit a biphasic response to hypoxia, with ventilation increasing and then declining. Our purpose was to define if this response could be supported by the pontile and medullary respiratory centers. Spontaneously breathing and paralyzed and ventilated decerebrate or anesthetized, vagotomized rats were studied from birth to 13 days thereafter. Peak integrated phrenic activity, or tidal volume, and frequency initially increased and then declined after inspired oxygen was reduced from hyperoxic to hypoxic levels; most animals became apneic in hypoxia. Apnea occurred in a greater proportion of animals and more quickly with more severe hypoxia. Following sectioning of the carotid sinus nerves, ventilatory activity declined with a change from hyperoxia to normoxia. We conclude that the biphasic ventilatory response to hypoxia represents a balance between synaptically-induced augmentations and reductions of brainstem neuronal activities. The carotid chemoreceptors play a fundamental role in the augmentations, and reductions appear dependent upon actions of hypoxia upon brainstem mechanisms.

Anesthesia↗

PubMed1994

Entrainment of respiration to rocking in premature infants: coherence analysis.

Vestibular influences on breathing pattern were investigated in 18 premature infants in the neonatal intensive care nursery. Respiratory abdominal movements were recorded while the babies were manually rocked at varying rates between 30 and 60 cycles/min (cpm). Coherence spectra were estimated between the respiratory and rocker signals, and their magnitudes were evaluated at the rocking frequency, with coherence spectra > 0.85 indicative of strong entrainment to rocking. At least one incident of entrainment was seen in 15 of 18 infants, with 2:1 ratios (2 breaths/rocker cycle) occurring at rocking frequencies of 30-40 cpm (8 of 18 subjects) and 1:1 entrainment at rates of 42-50 cpm (5 of 18 subjects). More complex synchronization was observed in three infants, with patterns consisting of alternans between 2:1 and 3:2 ratios (5:3 entrainment). Infants > 35 wk postconceptional age exhibited greater coherence to rocking than infants < 35 wk (P < 0.01), indicating a maturational change in the reflex may occur. Results show that the natural stimulation of rocking a newborn provides a phasic input to its respiratory pattern generator that is capable of resetting the system's oscillation and entraining its rhythm.

Aging↗

PubMed1991

Effect of acute hypoxia on respiration and brain stem blood flow in the piglet.

Changes in local brain stem perfusion that alter extracellular fluid Pco2 and/or [H+] near central chemoreceptors may contribute to the decrease in respiration observed during hypoxia after peripheral chemoreceptor denervation and to the delayed decrease observed during hypoxia in the newborn. In this study, we measured the changes in respiration and brain stem blood flow (BBF) during 2-4 min of hypoxic hypoxia in both intact and denervated piglets and calculated the changes in brain stem Pco2 and [H+] that would be expected to occur as a result of the changes in BBF. All animals were anesthetized, spontaneously breathing, and between 2 and 7 days of age. Respiratory and other variables were measured before and during hypoxia in all animals, and BBF (microspheres) was measured in a subgroup of intact and denervated animals at 0, 30, and 260 s and at 0 and 80 s, respectively. During hypoxia, minute ventilation increased and then decreased (biphasic response) in the intact animals but decreased only in the denervated animals. BBF increased in a near linear fashion, and calculated brain stem extracellular fluid Pco2 and [H+] decreased over the first 80 s both before and after denervation. We speculate that a rapid increase in BBF during acute hypoxia decreases brain stem extracellular fluid Pco2 and [H+], which, in turn, negatively modulate the increase in respiratory drive produced by peripheral chemoreceptor input to the central respiratory generator.

Animals↗

PubMed1990

Respiratory modulation of pre- and postganglionic lumbar vasomotor sympathetic neurons in the rat.

The respiratory contribution to the activity of lumbar vasomotor pre- and postganglionic neurons was compared with previously reported respiratory patterns in the activity of neurons in the rostral ventrolateral medulla (RVLM-SE). Two patterns of respiratory modulation were observed characterized by (1) a depression of activity during inspiration and a postinspiratory peak (n = 19), and (2) a peak of activity during inspiration (n = 3). These patterns were similar to those previously reported in RVLM-SE neurons. The latency from the phrenic burst to the onset of respiratory modulation was consistent with the conduction time from the RVLM to the sympathetic chain. This suggests that respiratory modulation observed in lumbar sympathetic activity originates, in part, in RVLM-SE neurons.

Animals↗

PubMed1990

Rostral ventrolateral medulla and sympathorespiratory integration in rats.

The respiratory modulation of the lumbar sympathetic nerve discharge (LSND) was examined in halothane-anesthetized, paralyzed, and vagotomized rats by means of phrenic nerve discharge (PND)-triggered histograms. The respiratory modulation was 1) proportional to PND amplitude during chemoreceptor activation with CO2 and 2) reduced at elevated arterial pressure. Bilateral injections of bicuculline [gamma-aminobutyric acid (GABA)A receptor antagonist, n = 5] into the rostral ventrolateral medulla (RVLM), but not into medullary raphe, reversibly increased mean arterial pressure (MAP) and resting LSND, decreased the baroreflex, reduced PND amplitude and central respiratory rate, and greatly magnified the respiratory modulation of LSND. Injections of strychnine (glycine receptor antagonist, n = 5) or phaclofen (GABAB receptor antagonist, n = 2) into RVLM were without effect. Injections of kynurenic acid (excitatory amino acid receptor antagonist) into RVLM (n = 8), but not raphe (n = 3), reduced PND amplitude, increased central respiratory rate, reduced MAP, elevated resting LSND slightly, and greatly reduced the respiratory modulation of LSND. These data suggest that the rostral tip of the ventrolateral medulla represents a critical link between the central respiratory rhythm generator and the vasomotor outflow. Also, it indicates that the respiratory modulation of SND does not involve a gating of the activity of the medullary neurons that convey baroreceptor information to RVLM sympathoexcitatory neurons.

Animals↗

PubMed1989

Effect of aortic balloon inflation on ventilation and brain stem blood flow in piglets.

Increases in brain stem blood flow (BBF) during hypoxia may decrease tissue PCO2/[H+], causing minute ventilation (VE) to decrease. To determine whether an increase in BBF, isolated from changes in arterial PO2 and PCO2, can affect respiration, we obstructed the thoracic aorta with a balloon in 31 intact and 24 peripherally chemobarodenervated, anesthetized, spontaneously breathing newborn piglets. Continuous measurements of cardiorespiratory variables were made before and during 2 min of aortic obstruction. Radiolabeled microspheres were used to measure BBF before and approximately 30 s after balloon inflation in eight intact and five denervated animals. After balloon inflation, there was a rapid increase in mean blood pressure in both the intact and denervated animals, followed within 10 s by a decrease in tidal volume and VE. In the intact animals, the decrease in VE after acute hypertension can be ascribed to a baroreceptor-mediated reflex. After peripheral chemobarodenervation, however, acute hypertension continued to produce a decrease in VE, which cannot be explained by baroreceptor stimulation. In these denervated animals, aortic balloon inflation was associated with an increase in BBF (13.1 +/- 2.7%; P less than 0.05). We speculate that the increase in BBF during hypoxia may contribute to the decrease in ventilation observed after carotid body denervation.

Animals↗

PubMed1987

The thermophysiology of the newborn infant.

The preterm newborn, although a homeotherm in the true sense of the word, has increased heat and water losses when compared to the adult and these large losses necessitate providing a thermal environment which can allow a minimal resting metabolic rate. The physician who cares for newborn infants must direct special attention to the maintenance of "normal" body temperature of the low-birth-weight infant, whose survival may depend on such careful management. However, the physiology of temperature control is important for almost every aspect of the management of these infants; the immediate adaptation to extrauterine life, requirements for oxygen and calories, growth and development, and the diagnosis of infection. An understanding of these interrelated areas is highly relevant to the successful management of a wide variety of clinical problems in the newborn period.

Body Temperature Regulation↗

PubMed1985

A noninvasive constant-flow method for measuring respiratory compliance in newborn infants.

The constant-flow properties of time-cycled ventilators can be used to measure infant respiratory mechanics. We used a pulse method that does not interrupt inflationary flow to measure lung compliance (Cl) and respiratory system compliance (Crs) of 16 infants who required assisted ventilation. When the infants were relaxed, constant-flow inflation produced transrespiratory pressure tracings with constant slope segments. We calculated pulse Crs from inflationary flow divided by the slope of the pressure tracing, and compared the results to static and dynamic Crs values determined by standard methods. The pulse method accurately measured static Crs (r = .93) with a low intrasubject coefficient of variation (3.4%). Pulse and static Crs values consistently exceeded dynamic Crs (p less than .005). Cl measured with each method exceeded Crs (p less than .05), but the magnitude was clinically unimportant. Pulse Crs is a noninvasive measurement of static respiratory system recoil which proved to be sensitive to changes in respiratory muscle tone.

Humans↗

PubMed1985

Aminophylline reduces hypoxic ventilatory depression: possible role of adenosine.

Newborn infants and animals typically exhibit a paradoxical ventilatory response to hypoxia. The depressive phase of the response has not been adequately explained. It has been suggested that hypoxia may cause the release of inhibitory neuromodulators which depress ventilation. We have postulated that the nucleoside, adenosine, may be involved because 1) it is rapidly released during hypoxia, 2) it depresses ventilation, and 3) theophylline, a competitive inhibitor, has successfully been used to treat apnea of prematurity. Herein we describe the effects of aminophylline on ventilation during hypoxia in the spontaneously breathing newborn piglet administered both rapidly after ventilatory depression has occurred (bolus) and before the onset of hypoxia (pretreatment). Ten percent oxygen breathing produced a typical biphasic ventilatory response. The decrease in minute ventilation was caused by a decrease in both tidal volume and respiratory frequency. The bolus administration of aminophylline reversed the depression in minute ventilation (p less than 0.001) by increasing tidal volume (p less than 0.002). Pretreatment with aminophylline decreased the amount of ventilatory depression (p less than 0.05) by preventing a decrease in respiratory frequency. We conclude that aminophylline, an adenosine antagonist, reduces the decrease in ventilation which occurs during hypoxia in the newborn. We speculate that adenosine may play a role in hypoxic ventilatory depression and respiratory control in the newborn.

Adenosine↗