Biomedical subjects

R D Guthrie

Publications and source records attributed to R D Guthrie.

At least 55 records · Page 3Linked to original sources

PubMed1990

Postnatal development of phrenic motoneurons in the cat.

The postnatal growth of phrenic motoneurons in the cat was studied using retrograde transport of horseradish peroxidase (HRP). The mean somal surface area of these developing motoneurons increased 2.5 times from day 3 to adult while the mean somal volume increased four-fold. This change in mean somal surface area during postnatal development was found to be correlated with the change in mean axonal conduction velocity measured from phrenic motoneurons.

Animals↗

PubMed1990

External intercostal muscle activity during acute hypoxia in the kitten.

The effects of acute hypoxia on the recruitment of external intercostal muscle activity were determined in 12 kittens, aged 14 to 36 days. The animals were anesthetized with 1.23 +/- 0.23% halothane and bipolar electrodes were placed in the costal and crural diaphragm and in dorsal external intercostal muscles. Acute hypoxia was induced by the animals breathing 13% oxygen; arterial gases were sampled during baseline conditions and at 1 and 5 min after induction of hypoxia. Peak-moving average (PA) and minute electromyogram (EMG) activity (PA x f) were recorded during baseline conditions and at 1 and 5 min after onset of acute hypoxia. At 1 min of acute hypoxia, PA and PA x f of the costal diaphragm, crural diaphragm, and external intercostal muscles were significantly increased above baseline values (P less than 0.01). After 5 min of acute hypoxia, PA of all three muscles remained elevated above baseline values (P less than 0.05) but PA x f returned toward baseline levels. Respiratory frequency remained unchanged during the hypoxic stimulus. These data document that the newborn is capable of increasing inspiratory external intercostal muscle EMG activity during acute hypoxia. We speculate that this phasic recruitment could be of physiologic benefit to the newborn by stabilizing the complaint chest wall and by increasing the contribution of rib cage expansion to tidal breathing.

Acute Disease↗

PubMed1990

Measurements of pulmonary mechanics prior to the elective extubation of neonates.

We measured total respiratory system compliance (CRS) and resistance (RRS) by the passive expiratory flow technique prior to the elective extubation of 61 neonates with a history of respiratory distress syndrome. Successful trials of extubation were characterized by a higher mean value of CRS when compared to trials that led to reintubation (1.52 vs. 1.10 mL/cm H2O, P = 0.004). Low values of CRS (0.9 mL/cm H2O or less) were invariably associated with extubation failure, whereas high values of CRS (1.3 mL/cm H2O or greater) were associated with extubation success in 94% of patients. A higher mean value of RRS was recorded in the group of infants who failed extubation when compared to those who were successful (0.22 vs. 0.17 cm H2O/mL/s, P = 0.042). We propose that measurements of pulmonary mechanics, particularly CRS, may be useful in identifying infants who will be at risk for extubation failure.

Airway Resistance↗

PubMed1990

Computer analyses of EEG-sleep in the neonate: methodological considerations.

Neonatal EEG interpretation can aid in the estimation of central nervous system maturation, as well as provide diagnostic and prognostic information of the high-risk infant. However, one cannot easily visualize the complex interrelationships coupling EEG and polysomnographic components of the EEG-sleep rhythm. This is particularly relevant for the preterm neonate, in whom a rudimentary sleep cycle has not yet been clearly delineated. Computer analysis can augment the information derived from the visual interpretation of scalp-generated EEG activity. Automated techniques for EEG-sleep analysis have only recently been applied to a neonatal population. Such studies have been limited to full-term rather than preterm infants and rely on conventional methods that assume stationarity of neurophysiologic signals. We describe a computer system that simultaneously compares behavioral and electrographic components of EEG-sleep in a manner that preserves the integrity of the signals over time, while investigating the time- and frequency-dependent relationships among signals. Strategies for on-line and off-line editing, data storage, and off-line signal processing are described. Computational algorithms regarding analyses of EEG power, motility, and cardiorespiratory data are being used to study the ontogeny of EEG-sleep in asymptomatic preterm and full-term neonates. Computer strategies are based on both principles of stationarity and nonstationarity of physiologic signals and are applied depending on the temporal resolution required for specific signal processing needs.

Computer Systems↗

PubMed1990

Myosin isoforms in neonatal rat extensor digitorum longus, diaphragm, and soleus muscles.

The postnatal elimination of embryonic and neonatal myosin isoforms in the rat extensor digitorum longus, diaphragm, and soleus muscles was compared using electrophoresis and immunohistochemical techniques. Electrophoresis of native myosin showed that neonatal bands were present in all three muscles on day 4 but were absent from the day 21 extensor digitorum longus muscle that exhibited its adult electrophoretic pattern. Mature electrophoretic banding patterns were present on days 60 and 125 in the diaphragm and soleus muscles, respectively. Immunohistochemical analysis indicated that embryonic myosin heavy chain was present in all day 4 samples but absent by day 21. Quantitative evaluation determined that the rate of elimination of neonatal myosin heavy chain (MHCneo) was faster in the extensor digitorum longus muscle than in the diaphragm, with the soleus muscle having the slowest rate of elimination of this isoform. Embryonic myosin light chain was detected by two-dimensional electrophoresis through day 8 in each of the muscles. These data indicate that postnatal elimination of MHCneo is tissue specific and time dependent but not governed by either activity level or rostral-caudal position.

Aging↗

PubMed1990

Expiratory abdominal muscle activity during ventilatory chemostimulation in piglets.

We examined abdominal muscle minute electromyographic (EMG) activity (peak moving time average EMG x respiratory rate) during eupnea, hyperoxic hypercapnia (8% CO2-40% O2-balance N2), and hypoxia (13% O2) in 12 anesthetized (0.5% halothane) newborn piglets. In addition, we assessed the role of vagal afferent pathways in the abdominal muscles' response to ventilatory chemostimulation by examining abdominal EMG activity (EMGab) before and after bilateral cervical vagotomy in five animals. Phasic expiratory EMGab was observed in 11 of 12 piglets during eupnea. Hypercapnia was associated with a sustained augmentation of minute EMGab (444 +/- 208% control). In contrast, hypoxia consistently augmented (1 min, 193 +/- 33% control) then diminished (5 min, 126 +/- 39% control) minute EMGab. Vagotomy resulted in a decline in peak moving time average EMGab by approximately one-half (48 +/- 18% control); the abdominal muscles' response to ventilatory chemostimulation, however, was qualitatively unchanged. We conclude that 1) expiration during eupnea in anesthetized newborn piglets is associated with phasic EMGab; 2) both hypercapnia and hypoxia augment minute EMGab; however, only hypercapnia is associated with sustained augmentation; and 3) although vagal afferents have a role in modulating the base-line level of EMGab, other extravagal mechanisms appear to determine the pattern of EMGab in response to ventilatory chemostimulation.

Abdominal Muscles↗

PubMed1990

Influence of gestational age on pharmacokinetics of alfentanil in neonates.

Alfentanil's small volume of distribution and short elimination half-life, coupled with its preservation of hemodynamic stability, make it a potentially useful drug for analgesia and anesthesia in neonates. The pharmacokinetics of alfentanil were studied in 5 infants born at 26-35 weeks' gestation and in 5 infants of greater than 36 weeks. All infants were studied in the first 3 days of life. After injection of 25 micrograms/kg alfentanil, there was no significant change in blood pressure or heart rate. No significant difference was observed in volume of distribution (0.84 +/- 0.48 l/kg vs. 0.82 +/- 0.30 l/kg), clearance (1.35 +/- 0.69 ml.kg-1.min-1 vs. 1.7 +/- 0.47 ml.kg-1.min-1), or effective half-life (455 +/- 111 min vs. 328 +/- 48 min) between the two groups. The pharmacokinetic values reported here for both preterm and full-term infants are significantly different from data reported for older children.

Alfentanil↗

PubMed1989

The activity pattern of phrenic motoneurons during the aspiration reflex: an intracellular study.

Membrane potential trajectories and discharge characteristics were measured intracellularly in 29 phrenic motoneurons of anesthesized, paralyzed and artificially ventilated cats during hypercapnic respiration and the aspiration reflex. Fifteen 'active' cells discharged spontaneously during inspiration, and the remaining 14 'quiescent' cells exhibited no discharge in spite of strong central respiratory drive. The mean membrane potential of the quiescent cells during inspiration (-62 +/- 4 mV) was significantly lower than the threshold level determined for the active cells -52 +/- 4 mV). The mean axonal conduction velocity was slower for the active (60.4 +/- 8.7 m/s) than quiescent cells (67.4 +/- 6.9 m/s). All phrenic motoneurons discharged during the aspiration reflex with maximum instantaneous frequencies ranging from 6 to 357 Hz. No differences were found for the maximum discharge frequency during the reflex between the active and quiescent cells. Although there were differences in the slopes of the depolarization during inspiration between the groups of cells, no such difference existed in the slopes during the aspiration reflex. The threshold level for the first spike during the reflex was the same as that during inspiration but the level for successive spikes became progressively less negative while spike amplitude decreased and duration increased. Stimulation of the nasopharynx to elicit the aspiration reflex was found to alter the timing of the subsequent respiratory cycles.

Action Potentials↗

PubMed1989

The postnatal growth of motoneurons at three levels of the cat neuraxis.

The postnatal growth of motoneuron cell bodies located in the brainstem, cervical and lumbosacral spinal cord was investigated using retrograde transport of horseradish peroxidase in kittens ages 2, 12, 30, 55, 82 and 114 postnatal days and in an adult. The motoneurons innervating an extrinsic tongue muscle, the genioglossus, reached their adult size by eight weeks after birth. In contrast, the phrenic motoneurons innervating the diaphragm achieved adult size by 12 weeks and the motoneurons innervating the medial gastrocnemius muscle continued to grow beyond the twelfth postnatal week. The sizes of these motoneurons relative to one another remained constant during periods of development.

Aging↗

PubMed1989

Costal and crural diaphragm, and intercostal and genioglossal electromyogram activities during spontaneous augmented breaths (sighs) in kittens.

Spontaneously occurring augmented breaths (sighs) are common in infants. The pattern of electrical activity of the inspiratory muscles of the thorax and upper airway during augmented breaths, however, has not been fully characterized in this less than fully mature age group. We therefore examined costal and crural diaphragm and external intercostal and genioglossal EMG activities during spontaneous augmented breaths (n = 46) in 10 anesthetized (1.35% halothane) 1-month-old kittens breathing room air. EMG responses were assessed by comparing the spontaneous augmented breaths (AB) to the five immediately preceding breaths (control). The peak moving time average EMG activity observed during the AB was 240 +/- 32% (mean +/- SD) of control for the costal diaphragm, 279 +/- 66% of control for the crural diaphragm, and 274 +/- 68% of control for the external intercostal muscle. The mean increase in EMG activity during the AB was not significantly different among these three muscle groups (P greater than 0.25). Genioglossal EMG activity during AB was observed in only 1 of 10 study animals. These results document that during AB in anesthetized kittens, activity of the thoracic inspiratory muscles (costal/crural diaphragm and external intercostal muscles) increase in parallel, suggesting that they are modulated in a uniform manner. The infrequent observance of genioglossal activity during AB suggests that either 1) halothane anesthesia depresses genioglossal activity more than diaphragmatic and intercostal activity during AB or 2) that genioglossal recruitment is not necessary to maintain upper airway patency during this period of heightened respiratory drive.

Analysis of Variance↗

PubMed1989

Postnatal growth of genioglossal motoneurons.

The postnatal growth of kitten genioglossal motoneurons were examined in six different age groups (newborn, 2, 4, 8, and 12 weeks and adult) using the technique of retrograde transport of horseradish peroxidase (HRP). The cell bodies of 100-150 motoneurons in each age group were analyzed in a transverse plane of section using standard techniques. Somatic genioglossal motoneuron growth occurred primarily along the major axis, which increased from 25.2 microns to 41.3 microns between birth and 8 weeks of postnatal age, after which time there was no further increase in either major or minor dimension of the cell body. The form factor decreased from 0.94 to 0.80 from birth to adulthood indicating an increased eccentricity of the cell body. The number of primary dendrites visible with this technique remained constant throughout the postnatal period. Calculated somal surface area increased in a linear fashion from birth through 8 weeks of postnatal life. There was no further increase in surface area beyond this age. The rate of increase in somal surface area with age was significantly different from both the rate of increase of animal weight and animal surface area with age. The correlations between the demonstrated immature genioglossal morphology and its cellular electrophysiology or integrated respiratory function remain unknown. The recent demonstration of decreased activation of the genioglossus muscle following airway occlusion in premature infants with apnea suggests that the relationships between developing genioglossal motoneuron structure and function warrant further investigation.

Aging↗

PubMed1989

Genioglossal recruitment during acute hypoxia and hypercapnia in kittens.

We examined genioglossal and diaphragmatic EMG activities in one- and two-month-old anesthetized kittens during acute exposures to hypoxic (13% or 10% O2) and hyperoxic hypercapnic (8% CO2/50% O2/balanced N2) gas mixtures. Phasic genioglossal EMG activity, frequently characterized by a combined inspiratory-expiratory discharge pattern, was observed in 3 of 8 one-month-old vs. 7 of 7 two-month-old kittens during hypercapnia (Chi-square P less than 0.05). The percentage of kittens recruiting genioglossal activity during hypoxic exposures was similar at both ages (1 month, 75%; 2 month, 83%). Analysis of the breath-by-breath response during trials of hypoxia in which genioglossal recruitment was observed, however, revealed that the one-month-old kittens exhibited phasic genioglossal activity in only 40 +/- 27% of the stimulated breaths, compared to 63 +/- 26% for the two-month-old ones (P less than 0.05) at each level of hypoxia. In this regard, the genioglossal response to hypoxia in one-month-old kittens was frequently characterized by early and only transient recruitment (when diaphragmatic activity was at its peak), while genioglossal recruitment was more sustained in two-month-old animals. These data indicate that genioglossal activity in kittens is often recruited during exposures to hypercapnia and hypoxia, and suggest that such recruitment is more frequent with increasing postnatal age.

Animals↗

PubMed1989

Effects of varying concentrations of halothane on the activity of the genioglossus, intercostals, and diaphragm in cats: an electromyographic study.

To determine the possible differential effects of depth of inhalation anesthetics on inspiratory muscle activity, the following were studied in seven adult cats: the phasic activity of the diaphragm, the external intercostals, and the genioglossus, by means of electromyography (EMG) and its moving time average (MTA). The animals spontaneously breathed 1.0-3.0% halothane in O2, while arterial PCO2 was maintained constant at approximately 60 mmHg by adjusting CO2 in the inspired gas mixture. Muscle activity was evaluated in terms of peak height of MTA, with measurements at 1% halothane used as control values. Halothane anesthesia attenuated inspiratory muscle activity significantly (P less than 0.05) in a dose-dependent fashion; muscle activity decreased most in the genioglossus, least in the diaphragm, and intermediately in the intercostals. Respiratory frequency, inspiratory time, and inspiratory duty cycle did not change significantly with increasing concentration of halothane.

Animals↗

PubMed1989

Visual and neurological outcome of infants with periventricular leukomalacia.

Visual acuity, visual fields and neurological status were assessed in 10 infants with periventricular leukomalacia (PVL), tested at 16, 36, 48 and 72 weeks from the expected date of confinement. Monocular acuity development was normal in eight of the 10 infants, but was below normal in one infant at eight months and in another at 18 months. Over half the infants tested at 16, 36 and 48 weeks had smaller visual fields than those of 95 per cent of healthy preterm infants tested at the same ages, but by 72 weeks only two of six infants tested had restricted visual fields. Nine of the 10 infants were neurologically abnormal at ages under one year, but only four remained so beyond one year. These results indicate more favourable outcomes for visual acuity and neurological status in infants with non-cavitary PVL than have been reported in infants with cavitary PVL. The most compromised infants were one with cavitary PVL and another with extensive non-cavitary PVL who had the longest-lasting EEG abnormalities of all 10 infants.

Aging↗

PubMed1989

Pharmacokinetics of alfentanil in newborn premature infants and older children.

Because developmental pharmacokinetics appear to be closely associated with anatomic and physiologic changes that occur with growth, we were interested in determining the disposition and elimination of alfentanil in premature infants and older children. The pharmacokinetic profile of alfentanil was determined in 6 premature infants requiring sedation for medical management or analgesia for stressful intensive-care procedures. These pharmacokinetic profiles were compared with pharmacokinetic profiles determined in 9 older infants and children undergoing operative procedures that required invasive monitoring. In both groups the plasma decay curves best fit a 2-compartment model. Compared with older children, premature infants demonstrated a significantly larger apparent volume of distribution (1.0 +/- 0.39 vs. 0.48 +/- 0.19 l/kg), a smaller clearance (2.2 +/- 2.4 vs. 5.6 +/- 2.4 ml/kg/min) and a markedly prolonged elimination half-life (525 +/- 305 vs. 60 +/- 11 min).

Age Factors↗

PubMed1988

Recruitment of intercostal muscle activity during hypercapnia in kittens.

Little is known about the respiratory behavior of the intercostal muscles within a neonatal and developmental context. We, therefore, examined intercostal muscle electromyographic (EMG) activity in kittens (1 month old, n = 8; 2 months old, n = 7) during eupnea and heightened respiratory drive induced by hypercapnia. The kittens were anesthetized with halothane (1.25-1.50%) at comparable minimum alveolar concentrations and were studied in the prone position during an acute exposure to hyperoxic hypercapnia (8% CO2, 50% O2, balance N2) for 7 min. We recorded EMG activities from bipolar electrodes embedded in the intercostal (dorsolateral thorax, 4th-5th interspace) (EMGic) and costal diaphragm (EMGdi) muscles. Peak moving time average EMG measurements served as our index of muscle activity. Phasic inspiratory EMGic activity was present during eupnea in all animals. EMGic and EMGdi increased significantly above baseline levels during hypercapnic exposure with the increase in EMGic (133 +/- 27%) being comparable to that observed in EMGdi (141 +/- 28%) (P = 0.40). No differences in EMGic (P = 0.64) or EMGdi (P = 0.88) recruitment were noted between age groups. These data indicate that hypercapnia augments intercostal muscle EMG activity in kittens and suggest that such activity parallels costal diaphragmatic EMG recruitment. We conclude that EMGic recruitment is a frequent respiratory phenomenon associated with hypercapnically stimulated diaphragmatic muscle activity in kittens. We speculate that intercostal muscle recruitment stabilizes the compliant chest wall of the newborn and helps sustain inspiratory force generation during stimulated breathing.

Animals↗

PubMed1987

Cerebral infarction in persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn and its attendant hypoxemia may place the infant at high risk for hypoxic-ischemic injury. In 19 infants with persistent pulmonary hypertension of the newborn, 16 of whom suffered intrapartum asphyxia, we evaluated a series of electroencephalograms (EEGs) for evidence of major focal cerebral injury, ie, persistent voltage attenuation and/or focal electrical-seizure activity. Of the 15 infants (78.9%) with such EEG findings, nine infants (47% of the total population) had cerebral infarction documented by cranial sonograms, computed tomographic scans, or autopsy findings. In eight (89%) of the nine infants with infarction, electrical seizures were noted during periods of muscle paralysis. We recommend (1) the use of electroencephalography in this population, particularly during periods of muscle paralysis, to detect underlying cerebrovascular lesions and (2) the use of cranial computed tomography if persistent, focal EEG abnormalities are noted.

Cerebral Infarction↗

PubMed1987

Early onset of airway reactivity in premature infants with bronchopulmonary dysplasia.

Pulmonary function during the early development of bronchopulmonary dysplasia (BPD) in premature infants is not well understood. Furthermore, it is not known how early airway reactivity appears in BPD. During a 14-month period we studied 32 infants (mean gestational age, 27.3 wk; mean birth weight, 1.02 kg) with respiratory distress syndrome in whom BPD eventually developed. We obtained maximal expiratory flow-volume (MEFV) curves by manual inflation of the lung followed by forced deflation with a negative pressure on 64 occasions (mean postnatal age, 43.1 days). At each test MEFV curves were obtained in 3 conditions: baseline; after normal saline aerosolization with manual ventilation as a control; and after bronchodilator. Maximal expiratory flow at 25% of FVC (Vmax25) was markedly decreased at baseline and remained decreased after saline control. The FVC also was decreased in both baseline and saline control studies. After bronchodilator there was a marked (p less than 0.001) increase in Vmax25 (+214% above saline control) together with a significant (p less than 0.001) increase in FVC (+21%). Of 23 infants studied after 3 wk of postnatal age, 21 exhibited a more than 30% increase in Vmax25 above control (defined as airway reactivity). The remaining 2 infants were already receiving bronchodilator therapy. The most premature infant with demonstrable airway reactivity was 26 wk postconception, and the youngest was 12 days old. In 13 infants who were studied initially before 3 wk of age, there was a highly significant correlation (r = 0.91 p less than 0.001) between the degree of airway reactivity and the severity of respiratory disease as determined by the duration of ventilator dependence. Airway reactivity may play an important role in the development and severity of BPD.

Airway Resistance↗