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Biomedical subjects

R D Guthrie

Publications and source records attributed to R D Guthrie.

At least 73 records · Page 4Linked to original sources
PubMed1987

Developmental changes in the ventilatory response of the newborn to added airway resistance.

Postnatal development of the steady-state response to inspiratory resistive loading was studied in eight 48-hour-old and seven 24-day-old tracheostomized monkeys. The newborn subjects did not maintain minute ventilation (Vl) with increasing loads of from 2 to 6 times baseline respiratory resistance, whereas the older subjects kept Vl constant when challenged by the same added resistances. The response patterns in both groups were characterized by a prolongation of Tl and Tl/Ttot, a reduction of respiratory frequency, and increases in airway occlusion pressure and respiratory work output. Apart from Vl, tidal volume (VT) was the only other ventilatory variable that differed significantly between age groups during loading. Arterial CO2 and O2 did not change from baseline in either group during loading, indicating that both age groups defended blood gas values equally well. The increases in occlusion pressures, inspiratory work output, and the maintenance of PaCO2 in the newborns indicated the presence of load compensatory mechanisms despite the fact that Vl was not strictly defended.

Aging↗
PubMed1986

Role of endogenous opiates in hypoxic ventilatory response in the newborn primate.

The effects of opiate receptor antagonism by naltrexone hydrochloride on the biphasic hypoxic ventilatory response in the infant Macaca nemestrina have been investigated. Minute ventilation, tidal volume, and respiratory frequency were measured in six animals from timed gestations before and during inhalation of a hypoxic gas mixture. All studies were completed in non-rapid-eye-movement sleep. Arterial blood gases were obtained during each stimulus period. All animals demonstrated the typical biphasic ventilatory response to acute moderate-severe hypoxemia. After the administration of naltrexone hydrochloride to block opiate receptors, the animals still manifested a biphasic hypoxic response that was no different than that noted prior to drug administration. Naltrexone hydrochloride had no effect on room air resting ventilation in any of the animals. Our data suggest that endogenous opiates play no physiological role in the acute ventilatory response to moderate-severe hypoxia in the newborn subhuman primate.

Animals↗
PubMed1986

Maternal smoking and infant respiratory distress syndrome.

The relationship between maternal smoking and infant respiratory distress syndrome (RDS) was investigated among 550 premature (36 weeks or less) births delivered at the University of Washington Hospital from 1977 to 1980. Forty-five percent of the mothers were smokers. To avoid bias due to the reduced birth weight of infants of smokers, infants of smokers and nonsmokers were compared within small gestational age categories (two-week intervals) and not by birth weight categories. Infants of mothers who smoked had a reduced incidence of RDS for their gestation compared with infants of nonsmokers. The probability of RDS (adjusted for gestational age and method of delivery) was 25% for the infants of smokers versus 38% for the infants of nonsmokers (odds ratio = 0.55, P = .005), equivalent to approximately a 1.5-week acceleration in lung maturity for infants of smokers. The smoking effect was not explained by demographic differences between smokers and nonsmokers, nor by differences in the incidence of pregnancy complications between the two groups. This study adds support to the theory that adverse pregnancy conditions may lead to an acceleration in pulmonary maturity to allow earlier extrauterine adaptation.

Female↗
PubMed1985

Ventilatory interaction between oxygen and carbon dioxide in the preterm primate.

The steady state ventilatory response to inhaled CO2 was measured in eleven unanesthetized premature Macaca nemestrina during the first 3 wk of life in different steady state background O2 mixtures hypoxia (FIO2 = 0.08 or 0.12), normoxia (FIO2 = 0.21) and hyperoxia (FIO2 = 0.96). Hyperoxic delta VI/delta PACO2 and delta P0.2/ delta PACO2 were significantly greater than hypoxic delta VI/ delta PACO2 and delta P0.2/delta PACO2, respectively, at both 2 and 21 days postnatal age by the Mann Whitney test of nonparametric ranking (2 days: 89.. and 80.2 degrees versus 88.7 and 56.4 degrees, respectively; 21 days: 89.3 and 76.6 degrees versus 50.2 and 57.1 degrees, respectively; p less than 0.05). Hypoxic delta VI/delta PACO2 was significantly depressed compared to normoxic delta VI/ delta PACO2 only at 21 days of age (50.2 versus 89.4 degrees, respectively; p less than 0.05); hyperoxic CO2 sensitivity and normoxic CO2 sensitivity did not differ at either age. The ventilatory interaction between O2-CO2 in the neonatal primate appears to be the inverse of the typical adult ventilatory interaction. It is hypothesized that differential changes in brain stem blood flow between neonates and adults might explain this difference in O2-CO2 ventilatory interaction.

Animals↗
PubMed1985

Influence of vagal activity on the neonatal ventilatory response to hypoxemia.

The sustained increase in ventilation (V1) that occurs during acute hypoxemia in adults is not characteristic of the neonate as V1 falls to or below baseline values soon after onset of the hypoxic stimulus. Associated with this decline in V1 is a decrease in tidal volume, lung compliance, inspiratory duration, and an increase in functional residual capacity and respiratory frequency. We hypothesized that hypoxemia induced small airway constriction and pulmonary time constant inequalities resulting in a frequency dependent fall in lung compliance and tidal volume and retention of lung volume. In seven newborn subhuman primates, responses to acute hypoxemia were measured prior to and after administration of atropine methyl bromide to prevent vagally mediated narrowing of peripheral airways. The increase in frequency and fall in inspiratory duration characteristic of the ventilatory decline during hypoxemia was eliminated by the drug but functional residual capacity and lung compliance were unaffected. Also, the initial rise in V1 was blunted or blocked in all subjects. Bilateral vagotomy caused V1 to fall significantly requiring oxygen supplementation but responses to hypoxemia were still biphasic in nature. These findings suggest that cholinergically mediated mechanisms in the airways do not alter effective lung distensibility related to respiratory rate. Acetylcholine may be important at the peripheral chemosensor since cholinergic blockade eliminated the initial ventilatory increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Sleep patterns in nonambulatory boys with Duchenne muscular dystrophy.

Sleep patterns and respiratory function during sleep were studied in five nonambulatory boys with Duchenne muscular dystrophy to clarify why patients with this disease awaken frequently at night. It was hypothesized that hypoxemia during sleep due to severe restrictive lung disease might cause nighttime arousals. Each boy underwent electroencephalography, electro-oculography and electromyography. Also determined were arterial oxyhemoglobin saturation, airflow from the nose and mouth, chest and abdominal excursions, and carbon dioxide tension of exhaled breaths. All five subjects had pulmonary function abnormalities consistent with severe restrictive lung disease and respiratory muscle weakness but none had evidence of respiratory failure or cor pulmonale. The boys awakened three times more frequently than age-matched published norms and experienced sleep stage shifts twice as often as normal children. Rapid-eye movement (REM) sleep as a proportion of total sleep was significantly reduced; sleep stage I was increased compared to normal values. No subject developed oxyhemoglobin desaturation during sleep. End-tidal CO2 tensions rose during sleep stages I, II and V (REM) in association with reduced chest wall excursion, suggesting transient episodes of mild hypoventilation which were not associated with arousals. Sleep fragmentation, frequent arousals and REM sleep deprivation occur in some boys with Duchenne muscular dystrophy but are not associated with significant disorders in breathing during sleep.

Adolescent↗
PubMed1984

Maturation of eupneic respiration in the neonatal monkey.

Comparison between 21 2-day-old infant monkeys and 17 21-day-old infants during non-rapid eye movement sleep demonstrated that minute ventilation (VI) increased from 141 +/- 30 to 257 +/- 65 ml/min secondary to elevations in tidal volume (VT) and mean inspiratory flow (VT/Ti) with little change in respiratory timing. These volumetric parameters of ventilation as well as functional residual capacity remained significantly augmented when standardized for gain in body weight. Dynamic lung compliance increased from 0.69 +/- 0.19 to 0.89 +/- 0.39 ml/cm H2O with age while inspiratory pulmonary resistance did not change. Effective elastance fell significantly with maturation (5.27 +/- 1.51 cm H2O/ml on day 2 versus 4.15 +/- 1.35 cm H2O/ml on day 21) while effective impedance was elevated postnatally. The postnatal ventilatory gain (80% increase in VI) was attributable to increases both in dynamic lung compliance (30%) and inspiratory effort (50%) as determined by esophageal pressure changes. Isometric occlusion pressures (P0.1, P0.2 . . . Pmax) also significantly increased during this time span, suggesting that the increased ventilation resulted from an elevated respiratory drive.

Aging↗
PubMed1983

Cerebral vascular resistance in premature infants.

The cerebral vascular bed is a low-resistance system in which continuous forward or advancing diastolic blood flow can be demonstrated. This advancing flow increases progressively with vasodilation and decreases or is absent when vessels are constricted. By using the Doppler technique, an indirect assessment of vascular resistance can be made by comparing systolic and diastolic flow amplitudes. We examined nine premature infants and found that respiratory acidosis alone, or hypoxia and acidosis in combination, resulted in significant vasodilation. This effect was reversible when arterial blood gas tensions returned to normal. The results indicate that within a physiologic range of BPs, premature infants with acute respiratory distress can alter their cerebral vascular resistance in response to spontaneous changes in blood gas tensions.

Acidosis↗
PubMed1983

A proposed neuropathological basis for learning disabilities in children born prematurely.

This study aimed at providing understanding of the etiology and mechanisms responsible for the learning and behavioral disabilities in the increasing numbers of survivors of neonatal intensive care units who develop MBD/LD-type (minimal brain dysfunction, learning disabilities) complications. The brains of 16 premature infants who died within the first month of life were studied by microscopic examination. Significant neuropathological findings in gray-matter and white-matter were found in many areas, including both superficial cortical and deep basal brain structures. These lesions are postulated to be precursors to later LD and MBD syndromes in infants who survive, such that similar lesions of varying severity correlate with varying degrees of brain dysfunction. Premature infants who survive are known from other studies to be high-risk candidates for LD- and MBD- type developmental disabilities.

Brain↗
PubMed1983

Dopamine and carotid body function in the newborn lamb.

The effect of dopamine on the acute ventilatory response to hypoxia was investigated in four newborn lambs studied on the 1st day of postnatal life and eight lambs studied between 7 and 12 days of age. Studies were accomplished during nonrapid-eye-movement sleep in unanesthetized tracheotomized animals. Changes in minute ventilation (VE/kg), tidal volume, and frequency induced by intravenous bolus injection of dopamine (10 micrograms/kg) or saline control were assessed while animals were breathing room air or N2, before and after carotid body denervation (CBD). Dopamine depressed resting ventilation at both postnatal ages. This effect was greater in the older animals. Dopamine blunted the hypoxia-induced increase in VE/kg at both ages. The magnitude of this depression did not vary with postnatal age. Dopamine induced cessation of respiratory effort at end expiration (apnea) during room air and N2 breathing significantly more often in the older animals. The effect of dopamine was mediated at the carotid body. CBD decreased ventilation by an increase in breath-to-breath interval in older animals, suggesting carotid sinus nerve afferent activity is more important during eucapnic respiration in older animals than in the immediate newborn period.

Animals↗
PubMed1983

Pulmonary mechanics during the ventilatory response to hypoxemia in the newborn monkey.

Dynamic lung compliance (CL), inspiratory pulmonary resistance (RL), and functional residual capacity (FRC) were measured in 10 unanesthetized 48 h-old newborn monkeys and seven 21-day-old infant monkeys during acute exposures to an equivalent level of hypoxemia. End-expiratory airway occlusions were performed and the pressure developed by 200 ms (P0.2) was utilized as an index of central respiratory drive. P0.2 demonstrated a sustained increase throughout the period of hypoxemia on day 2 despite the fact that minute ventilation (VI) initially increased but then fell back to base-line levels. Dynamic lung compliance fell and FRC increased by 5 min of hypoxemia in the newborns. The 21-day-old monkeys exhibited a sustained increase in both VI and P0.2 throughout the hypoxic period with no change in CL and FRC. RL did not change at either postnatal age during hypoxemia. These data indicate that the neonatal monkey is subject to changes in pulmonary mechanics (decreased CL and increased FRC) during hypoxemia and that these changes are eliminated with maturation.

Airway Resistance↗
PubMed1982

Power spectral analysis of the neonatal primate electroencephalogram during acute hypoxemia.

The effect of acute graded hypoxemia on the electroencephalogram (EEG) of five prematures and five full term Macaca nemestrina in the neonatal period was determined using power spectral analysis--a technique that obviates the limitations of visual inspection. The EEG of selected epochs was analyzed by a Fast Fourier Transform program (POWER) during the 20 min of each trial of hypoxemia and compared with simultaneous arterial oxygen tensions. Levels of hypoxemia were graded as profound (PaO2=15-25 Torr); severe (PaO2=26-35 Torr), moderate (PaO2=36-50 Torr), or mild (PaO2=51-75 Torr). The EEG during normoxemia had a band width of 0.5 to 10 Hz and a peak power at 1-3 Hz. During mild hypoxemia, an increase in power in the delta range (0-3.5 Hz) occurred in the oldest animals. At moderate hypoxemia, the youngest animals showed a depression of absolute power in the delta band. A slowing of the EEG and decrease in power in the theta frequency range (4-8 Hz) followed when severe hypoxemic levels are reached. During profound hypoxemia, all animals at each postnatal age exhibited a significant decrease in EEG power at the delta and theta frequencies (P less than 0.025) except 3-wk-old full term animals in which there was no significant change in the delta band. These results clarify and extend previously reported effects of hypoxemia on the neonatal EEG.

Animals↗
PubMed1981

Development of CO2 sensitivity: effects of gestational age, postnatal age, and sleep state.

To determine the independent effects of sleep state, gestational age, and postnatal age on eucapnic ventilation and steady-state CO2 sensitivity, nine premature (146 +/- 3 days) and eight full-term (168 +/- 2 days) monkeys, Macaca nemestrina, from accurately timed conceptions were studied serially over the first 3 wk of life. Minute volume (VE)/kg,tidal volume (VT)/kg, and respiratory frequency were quantitated during rapid-eye-movement sleep (REM) and nonrapid-eye-movement sleep (NREM)in room air and when animals were breathing varied concentrations of cO2 in 21% O2. Eucapnic VE/kg and CO2 sensitivity [(deltaVE/kg)/delta PaCO2] increased progressively with advancing postnatal age during NREM sleep in grouped term and premature animals. CO2 sensitivity was not significantly different between REM and NREM sleep except in full-term animals at the highest postconceptual age studied (189 +/- 2 days) when [(delta VE/kg)/delta PaCO2] was lower in REM sleep than in NREM sleep (209 +/- 54 vs. 301 +/- 71 ml.min-1.kg-1.Torr-1; P less than 0.05, paired-t test). Gestational age had no measurable effect on eucapnic ventilation or CO2 sensitivity. These results support the hypothesis that REM sleep-induced depression of CO2 sensitivity develops in the neonatal monkey with advancing postconceptual age.

Aging↗
PubMed1981

Occlusion pressures during the ventilatory response to hypoxemia in the newborn monkey.

End-expiratory airway occlusions were performed in eight unanesthetized premature newborn monkeys during acute hypoxemia to investigate mechanisms involved in the newborn's biphasic ventilatory response to hypoxia. Two-day-old monkeys demonstrated an immediate increase in minute ventilation (VI) and a decrease in PaCO2 followed within 5 min by a return of VI and PaCO2 to base-line levels. The decline in VI was associated with a decrease in tidal volume (VT) and inspiratory flow (VT/TI) and an increase in respiratory frequency. Occlusion pressures (PO.2) remained elevated throughout the hypoxic stimulus, and end-expiratory lung volume increased during the late response. "Effective" impedance (P0.1/V0.1, P0.2/V0.2, etc.) and "effective" elastance (Pmax/VT) were also elevated. At 21 days of age, the monkeys demonstrated a sustained ventilatory response as VI, VT, VT/TI, and P0.2 remained elevated throughout the period of hypoxemia. End-expiratory lung volume increases as on day 2, but effective impedance and effective elastance did not change. These data suggest that the biphasic response to hypoxia in the newborn may result from a change in respiratory timing and an alteration in respiratory mechanics and is not due to a decrease in central respiratory drive.

Airway Obstruction↗
PubMed1981

Hypoxic ventilatory response in the newborn monkey.

The hypoxic ventilatory response was determined in twelve unanesthetized newborn monkeys, Macaca nemestrina. Measurements of blood gases and ventilation were made during normoxia and hypoxia at the postnatal ages of 2, 7, and 21 days. Data were collected during quiet sleep. The infant monkey demonstrated a definite but transient hyperventilatory response following exposure to a FiO2 of 0.12 or 0.14 on the second day of life. Baseline ventilation increased 15% (Fi02=0.14) and 28% (Fi02=0.12) after 1 minute of hypoxia; p less than 0.05 in both instances. Return to baseline ventilation occurred between 3 and 5 minutes after hypoxic stimulus onset. This biphasic response to hypoxia converted to an adult-like, sustained hyperventilation during the ensuing three weeks of postnatal maturation. Episodes of periodic breathing and/or apnea were noted to occur during the induced hypoxemia. These data demonstrate that the infant subhuman primate has a ventilatory response to hypoxia that is similar to that of the human infant and is an excellent model for the study of the maturation of the respiratory control system.

Animals↗
PubMed1981

Intracranial hemorrhage in premature infants: accuracy in sonographic evaluation.

The real-time high resolution mechanical sonographic sector scanner is a convenient and useful instrument for the detection of intracranial hemorrhage in premature infants. Experience with 27 infants with intracranial hemorrhage detected by sonography and confirmed by computed tomography (CT) or by autopsy is analyzed. The severity of the hemorrhage shown by those methods was graded by an accepted classification for standardized reporting. The extent of intraparenchymal and intraventricular hemorrhage was accurately assessed by sonography in all cases except for small amounts of blood in normal sized ventricles in five of 12 instances. Sonography also failed to detect subarachnoid hemorrhage in each of 13 cases. There were no known false-positive sonograms. From this experience the authors believe sonographic sector scanning should be the initial examination in all infants at high risk for intracranial hemorrhage. When the ventricles are of normal size, CT scanning is recommended to search for small intraventricular hemorrhage that may not be detected by sonography. For subarachnoid bleeding, CT is preferable to sonography.

Cerebral Hemorrhage↗