Biomedical subjects

E N Bruce

Publications and source records attributed to E N Bruce.

At least 37 records · Page 2Linked to original sources

PubMed1993

Hyperoxic exposure of developing rat lung decreases tropoelastin mRNA levels that rebound postexposure.

These studies were undertaken to determine whether tropoelastin message expression in lung parenchymal tissue is altered in rats reared in an hyperoxic environment during the period of time that alveolar septation normally occurs. Rat pups were exposed to > 95% oxygen from days 4 to 14 and killed during the exposure and recovery periods. Results of in situ hybridizations indicated a delay in peak tropoelastin (TE) message levels in oxygen-exposed rats vs. controls, day 16 vs. day 11, respectively. In addition, lung parenchymal TE mRNA levels in the oxygen-exposed pups remained elevated through day 23, 1 wk after TE mRNA levels had decreased in controls. These observations suggest that the regulatory control of elastin synthesis during lung alveolar septation is altered by hyperoxic exposure. In a separate experiment, rat pups were exposed to > 95% oxygen during the period of alveolarization and followed for 4 wk postexposure. Pulmonary function measurements were conducted to determine whether lung function was altered postexposure and, if so, whether recovery occurred. We also used stereological techniques to quantitate the total length of lung parenchymal elastic fibers to determine whether elastic fiber content in the oxygen-exposed pups was restored to normal levels during the month postexposure. Although the total length of elastic fibers in lung parenchyma was found to be greater in oxygen-exposed than control pups from postnatal days 22 to 41, pressure-volume curves indicated that lungs of the oxygen-exposed pups tended to be more compliant than controls, suggesting that abnormal elastic fiber assembly might have been a contributing factor.

Aging↗

PubMed1993

Bifurcations of the respiratory pattern associated with reduced lung volume in the rat.

Rats with intact vagal reflexes exhibit patterns of breathing that contain greater degrees of freedom than those seen after vagotomy. To determine how alterations in end-expiratory volume modify the respiratory pattern, continuous positive (CPAP) and negative (CNAP) airway pressure was applied to tracheal openings of nine urethan-anesthetized vagi-intact rats (+3 to -9 cmH2O). Phase portraits (e.g., volume vs. flow curves), power spectra, correlation integral curves, and inspiratory-to-expiratory duration (TI/TE) ratios are used to interpret the vagal-dependent responses to changes in mean tracheal pressure (Ptr). With CPAP, respiratory oscillation was highly periodic and one dimensional, with TI/TE near 1.0. As Ptr was reduced in a stepwise manner, transient bursts of inspiratory airflow developed local to the expiratory-inspiratory transition, with amplitude increasing proportionally with the level of CNAP. These oscillatory "expiratory interrupts" (doubling TI/TE in five of nine cases) produced highly variable and asymmetric respiratory patterns. Progressive increases in correlation dimension (maximum = 1.8-3.0) and tendencies toward broadband power spectra were seen as Ptr was lowered. The irregular phase-switching dynamics seen with CNAP (which disappeared after vagotomy) are consistent with onset of low-dimensional chaos, probably correlated with activation of feedback mechanisms responsive to lung deflation.

Algorithms↗

PubMed1993

Role of deflation-sensitive feedback in control of end-expiratory volume in rats.

Rats breathing from reduced end-expiratory volumes (EEV) exhibit transient bursting of inspiratory airflow local to the expiratory-inspiratory transition (E-I) accompanied by increases in inspiration-to-expiration duration ratio. Continuous positive (CPAP) and negative (CNAP) airway pressures (+3 to -9 cmH2O) were applied to tracheal openings of 17 unilaterally vagotomized rats (urethan anesthetized) to evaluate the feedback mechanisms associated with these oscillatory "expiratory interrupts." Whole nerve recordings of afferent vagus (Vag) were primarily inspiratory with CPAP. As tracheal pressure was reduced in a stepwise manner, progressive decreases in inspiratory peaks and increases in activity during late expiration were seen on Vag. Single-fiber recordings correlate Vag expiratory activity with slowly adapting receptors sensitive to lung deflation. With CNAP, 1) progressively earlier onsets of activity in inspiratory muscles (e.g., diaphragm, genioglossus, posterior cricoarytenoid) were observed (increased inspiratory duration, decreased expiratory duration); oscillations at E-I developed only when expiratory peaks on Vag were significant. 2) Thyroarytenoid muscle exhibited onset of electromyographic activity that immediately succeeded onset of Vag during late expiration. When the trachea is intact, these two actions might combine to produce a respiratory pattern similar to the "grunting" often seen in newborns breathing from reduced EEVs. In contrast to larger mammals, rats rely strongly on deflation reflexes for control of E-I phase switching, presumably to aid in maintenance of an elevated EEV.

Animals↗

PubMed1993

Bifurcations of the respiratory pattern produced with phasic vagal stimulation in the rat.

Geometric methods from nonlinear dynamics are employed to evaluate dynamic processing of vagal afferent information by the respiratory central pattern generator (RCPG). While measuring airflow and diaphragm EMG, we applied brief electrical stimuli (40- to 130-ms duration) to one afferent vagus of bilaterally vagotomized urethan-anesthetized rats during every breath at various phases of the respiratory cycle. Stimuli applied during early or late inspiration of every breath evoke highly predictable one-dimensional responses: reversible (graded inhibition) or irreversible (off-switching) inhibition of inspiratory activity, respectively. Stimulation during midinspiration produces higher-dimensional oscillations that wander unpredictably over a continuum of graded inhibition and off-switching; "spiral" attractors and "horseshoe" return maps at this phase are characteristic of Silnikov's bifurcation. Stimuli applied during early expiration always prolonged expiratory duration, but those delivered during midexpiration evoked unpredictable wandering between prolongations and shortening of expiratory duration. A narrow time window surrounds the expiratory-inspiratory (E-I) transition, where stimuli elicit either breaths of short duration and low amplitude (irreversible E-I transition, decreased total respiratory cycle duration) or transient bursts of inspiratory activity at the E-I transition followed by a prolonged breath (reversible E-I transition, increased total respiratory cycle duration). We conclude that RCPG "gating" of and adaptation to vagal feedback combine to produce complex breath-to-breath dynamics in the rat that are consistent with low-dimensional chaos.

Anesthesia↗

PubMed1993

Adaptive buffering of breath-by-breath variations of end-tidal CO2 of humans.

We have designed and implemented a computer-controlled system that uses an adaptive control algorithm (generalized minimum variance) to buffer the breath-by-breath variations of the end-tidal CO2 fraction (FETCO2) that occur spontaneously or are exaggerated in certain experimental protocols (e.g., induced hypoxia, any type of induced variations in the ventilatory pattern). Near the end of each breath, FETCO2 of the following breath is predicted and the inspired CO2 fraction (FICO2) of the upcoming breath is adjusted to minimize the difference between the predicted and desired FETCO2 of the next breath. The one-breath-ahead prediction of FETCO2 is based on an adaptive autoregressive with exogenous inputs (ARX) model: FETCO2 of a given breath is related to FICO2, FETCO2 of the previous breath, and inspiratory ventilation. Adequacy of the prediction is demonstrated using data from experiments in which FICO2 was varied pseudorandomly in wakefulness and sleep. The algorithm for optimally buffering changes in FETCO2 is based on the coefficients of the ARX model. We have determined experimentally the frequency of FETCO2 variations that can be buffered adequately by our controller, testing both spontaneous variations in FETCO2 and variations induced by hypoxia in young awake human subjects. The controller is most effective in buffering variations of FETCO2 in the frequency range of <0.1 cycle/breath. Some potential applications are discussed.

Adaptation, Physiological↗

PubMed1992

Long-lasting ventilatory response of humans to a single breath of hypercapnia in hyperoxia.

It has often been assumed that under normoxia, closed-loop ventilatory responses to transient CO2 stimulation (i.e., lasting for 1-3 breaths) are less likely to be mediated by the slow-responding central (medullary) chemoreflex. This assumption, however, has not been quantitatively examined in humans. We hypothesized that in the closed-loop respiratory chemical feedback system [in which the centrally mediated ventilatory response to transient changes in the arterial PCO2 levels (PaCO2) will in turn affect the pulmonary CO2 and hence PaCO2], the contribution of the central chemoreflex pathways to brief disturbances in blood gases may be more important than considered previously. Using the technique of pseudorandom binary CO2 stimulation, we quantified the ventilatory response of normal humans to brief disturbances in arterial CO2 during hyperoxia. Tidal volume (VI), inspiratory ventilation (VI), inspiratory time (TI), expiratory time (TE), and end-tidal CO2 fraction (FETCO2) were measured in subjects who inhaled a mixture that was pseudorandomly switched between 95% O2-5% CO2 and 100% O2 (63 breath sequences). From these data, we calculated the responses of VI, VI, TI, TE, and FETCO2 to a single-breath inhalation of 1% CO2 in O2. Our results showed that in response to a brief increase of 0.75 Torr in alveolar CO2, VI showed a transient increase (average peak response of 0.12 1/min) that persisted for greater than or equal to 80 s in every subject. The response of VI was similar to that of VI, whereas TI and TE showed no consistent changes. Using these results we calculated that central chemoreflex pathways may contribute significantly to typical transient CO2 stimulation tests in hyperoxic and normoxic humans.

Adult↗

PubMed1991

The role of midline ventral medullary structures in generation of respiratory motor high frequency oscillations.

Lesions 1-2 mm deep in the midline of the ventral medulla (VM) abolished high frequency oscillations (HFO) in the respiratory motor output in cat and rabbit. Raising arterial pCO2 increased phrenic nerve activity to its prelesion level but did not restore HFO. We conclude that the neuronal pathways crossing the midline of the VM are crucial for reinforcement of respiratory activity and HFO generation.

Animals↗

PubMed1991

Cardiorespiratory responses to glutamatergic antagonists in the caudal ventrolateral medulla of rats.

The role of caudal ventrolateral medullary (CVLM) depressor neurons in influencing arterial pressure and ventilation as well as the baroreflex control of arterial pressure was investigated, and the part played by excitatory N-methyl-D-aspartate (NMDA) and non-NMDA receptors in mediating the responses was determined. In urethane-anesthetized, spontaneously breathing rats unilateral microinjections into the caudal depressor area of the broad-band glutamatergic antagonist kynurenic acid (KYN, 5 nmol or 1.58 nmol), or NMDA antagonist 2-amino-5-phosphonovaleric acid (2-APV, 2.7 nmol), or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 0.257 nmol) caused a respiratory arrest within 4 min and the animals had to be artificially ventilated. Respiratory frequency increased on injecting KYN and CNQX while it did not change significantly with 2-APV. Apnea resulted from progressive decrease in tidal volume. During the apnea ventilation with 5% CO2 did not revive breathing. Mean arterial pressure (MAP) increased significantly with KYN and 2-APV injections but not with CNQX. The baroreflex decrease of MAP, elicited by left or right aortic depressor nerve stimulation, was significantly reduced or abolished after bilateral microinjections of all 3 antagonists. Ventilation as well as the baroreflex usually recovered after 1-1.5 h. Microinjections of the same doses of antagonists into the facial nucleus, as well as application of KYN (25 nmol) to the ventral medullary surface above the hypoglossal rootlets, had no significant effect. The results support previous findings that the CVLM neurons of the rat inhibit sympathetic neurons providing the vasomotor tone, and that an intact CVLM is obligatory for mediating the baroreflex decrease of arterial pressure. The results also indicate that: (1) the CVLM is essential for sustaining ventilation in the rat; (2) only NMDA receptors are involved in maintaining baseline blood pressure while both NMDA and non-NMDA receptors mediate the baroreceptor depressor reflex; and (3) both NMDA and non-NMDA receptor activation is necessary to sustain ventilation.

2-Amino-5-phosphonovalerate↗

PubMed1991

Mathematical model of cellular basis for the respiratory sinus arrhythmia.

The respiratory sinus arrhythmia (RSA) is a vagally mediated oscillation in cardiac cycle length at the frequency of breathing. We developed a mathematical model that predicted the temporal and frequency dependence of the RSA. We used the mathematical model to examine the underlying cellular basis for the RSA at the level of the sinus node. We alternated efferent vagal activity between a low and a high frequency at the frequency of breathing. This oscillation caused the rate of acetylcholine (ACh) release to oscillate between a low and a high rate at the frequency of breathing. ACh degradation followed linear pharmacokinetics for physiological concentrations of ACh. Therefore, the concentration of ACh in neuroeffector junctions of the sinus node oscillated at the frequency of breathing. Membrane potential responded rapidly to changes in the concentration of ACh relative to the rate of ACh degradation. Thus, the time course of the RSA depended on the rate of ACh degradation. Membrane potential oscillated at several integer multiples of frequency of breathing and at various higher frequencies, which were integer multiples of the frequency of breathing and the frequencies of firing of the sinus node. However, computing cardiac cycle length from membrane potential eliminated the higher frequencies. Therefore, cardiac cycle length oscillated at several integer multiples of the frequency of breathing, but not at these higher frequencies.

Acetylcholine↗

PubMed1991

Alteration of phrenic high frequency oscillation by local cooling of the ventral medullary surface.

Cooling of small sites on the ventral medullary surface of the cat produces a decrease in frequency of phrenic high frequency oscillation (HFO). The effect on HFO frequency of cooling near the hypoglossal rootlets, but not the effect of cooling near the inferior cerebellar artery, can be completely offset by raising arterial pCO2 to restore phrenic activity to its precooling level. Thus, structures near the ventral medullary surface are important for generation or propagation of phrenic HFO. The effect of cooling of the 'intermediate area' cannot be entirely explained as depression of putative central chemoreceptor activity.

Animals↗

PubMed1991

Contribution of chemical feedback loops to breath-to-breath variability of tidal volume.

We tested whether chemical feedback loops contribute to the breath-to-breath correlations seen in respiratory cycle parameters. We have analyzed tidal volume (VT) of seven anesthetized, vagotomized, spontaneously breathing rats and the peaks of the 'integrated' phrenic neurograms (P) of another twelve anesthetized, vagotomized, paralyzed and artificially ventilated rats. Animals were studied while breathing 100% O2, 4% CO2 in O2 and/or room air. Our analysis consisted of fitting a first-order autoregressive (AR1) model to each measured variable in steady-state conditions. We found that: (1) breath-to-breath fluctuations of VT could be described by a first-order autoregressive model in which the fluctuation of VT on each breath from its mean level is correlated with that of the immediately preceding breath; (2) breath-to-breath fluctuations of P were not correlated with those of previous breaths, because successive values of P were uncorrelated random variables. Hypercapnia enhanced correlations in VT (3 rats) but not in P (12 rats). We propose that breath-to-breath correlations of VT in anesthetized, vagotomized and spontaneously breathing rats may reflect the effects of noise in respiratory chemical feedback loops.

Animals↗

PubMed1991

Vagal afferent activity increases dynamical dimension of respiration in rats.

Geometric and numerical techniques from nonlinear dynamics are employed to characterize the respiratory patterns of adult rats. In phase space constructions from volume measurements, the respiratory behavior of the vagotomized rat is seen to be unimodal and periodic, whereas that of the vagi-intact animal is bimodal and sensitive to initial conditions and displays stretching and folding of trajectories. By use of the correlation integral, the dimension and entropy were estimated for the respiratory patterns of five urethan-anesthetized rats (before and after vagotomy) and two awake animals (resting, vagi intact only). The results indicate that the central respiratory pattern of the anesthetized vagotomized rat behaves primarily as a single degree-of-freedom oscillator, which can be moved into a regime of low-order chaos in the presence of feedback from pulmonary stretch receptors, contributing significantly to the variability observed in the respiratory pattern of the vagi-intact animal. A model designed to emulate the Hering-Breuer inflation reflex demonstrates that the inspiration-inhibiting action of the reflex interacting with the oscillator at a critical phase transition is sufficient to drive the central pattern generator output into low-order chaos.

Afferent Pathways↗

PubMed1990

Neural network implementation of a three-phase model of respiratory rhythm generation.

A mathematical model of the central neural mechanisms of respiratory rhythm generation is developed. This model assumes that the respiratory cycle consists of three phases: inspiration, post-inspiration, and expiration. Five respiratory neuronal groups are included: inspiratory, late-inspiratory, post-inspiratory, expiratory, and early-inspiratory neurons. Proposed interconnections among these groups are based substantially on previous physiological findings. The model produces a stable limit cycle and generally reproduces the features of the firing patterns of the 5 neuronal groups. When simulated feedback from pulmonary stretch receptors is made to excite late-inspiratory neurons and inhibit early-inspiratory neurons, the model quantitatively reproduces previous observations of the expiratory-prolonging effects of pulses and steps of vagal afferent activity presented in expiration. In addition the model reproduces expected respiratory cycle timing and amplitude responses to change of chemical drive both in the absence and in the presence of simulated stretch receptor feedback. These results demonstrate the feasibility of generating the respiratory rhythm with a simple neural network based on observed respiratory neuronal groups. Other neuronal groups not included in the model may be more important for shaping the waveforms than for generating the basic oscillation.

Animals↗

PubMed1990

Stability analysis of CO2 control of ventilation.

A theoretical analysis of the CO2 control of the respiratory system is presented using both analytic and simulation techniques. A stability index (SI) is obtained by linearizing a dynamic first-order model with a time delay. Analytically, SI values greater than unity predict an unstable response to a disturbance. Because the first-order model is reduced from a higher-order physiological model, SI can be algebraically related to physiological parameters. This relationship shows that SI increases with a decrease in system tissue volume, metabolic rate, or inspired CO2 partial pressure; SI decreases with a decrease in time delay, cardiac output, controller gain, or controller intercept. Analytically, SI distinguishes stable from unstable domains. By simulations of the nonlinear first-order model, three domains are obtained: an unstable domain (sustained oscillations, SI greater than 1.1), an underdamped stable domain (transient oscillations, 0.3 less than SI less than 1.1), and an overdamped stable domain (no oscillations, 0 less than SI less than 0.3). With this classification, disturbances such as change of state (e.g., from awake to asleep) or sigh may produce transient oscillations if the system becomes underdamped even though stable. Potential applications of this work include quantitative distinction of the physiological factors in control disorders associated with short-term periodicities (e.g., Cheyne-Stokes breathing, sleep apnea, breathing at altitude).

Carbon Dioxide↗

PubMed1990

Nonrandom variability in respiratory cycle parameters of humans during stage 2 sleep.

We analyzed breath-to-breath inspiratory time (TI), expiratory time (TE), inspiratory volume (VI), and minute ventilation (Vm) from 11 normal subjects during stage 2 sleep. The analysis consisted of 1) fitting first- and second-order autoregressive models (AR1 and AR2) and 2) obtaining the power spectra of the data by fast-Fourier transform. For the AR2 model, the only coefficients that were statistically different from zero were the average alpha 1 (a1) for TI, VI, and Vm (a1 = 0.19, 0.29, and 0.15, respectively). However, the power spectra of all parameters often exhibited peaks at low frequency (less than 0.2 cycles/breath) and/or at high frequency (greater than 0.2 cycles/breath), indicative of periodic oscillations. After accounting for the corrupting effects of added oscillations on the a1 estimates, we conclude that 1) breath-to-breath fluctuations of VI, and to a lesser extent TI and Vm, exhibit a first-order autoregressive structure such that fluctuations of each breath are positively correlated with those of immediately preceding breaths and 2) the correlated components of variability in TE are mostly due to discrete high- and/or low-frequency oscillations with no underlying autoregressive structure. We propose that the autoregressive structure of VI, TI, and Vm during spontaneous breathing in stage 2 sleep may reflect either a central neural mechanism or the effects of noise in respiratory chemical feedback loops; the presence of low-frequency oscillations, seen more often in Vm, suggests possible instability in the chemical feedback loops. Mechanisms of high-frequency periodicities, seen more often in TE, are unknown.

Adult↗

PubMed1989

Tonic and baroreflex effects on arterial pressure and ventilation of pentobarbital and nicotine on the rat ventral medullary surface.

Unilateral aortic depressor nerve stimulation caused depression of arterial pressure (baropressure reflex) and ventilation (baro-ventilatory reflex) in urethane-anesthetized, spontaneously breathing Sprague-Dawley rats. Application of sodium pentobarbital to the ventral medullary surface (VMS) depressed baseline arterial pressure and ventilation, and attenuated the baro-pressure reflex, but not the baro-ventilatory reflex. Application of nicotine on the VMS decreased baseline arterial pressure and increased ventilation, but left both baro-pressure and baro-ventilatory reflexes unaltered. The results suggest that some of the structures that affect vasomotor tone may not be involved in the baroreflex inhibition of arterial pressure. Additionally, neither the neural structures near the VMS which modulate CO2 control of ventilation, nor those that affect tonic control of vasomotor tone are likely to be significantly involved in the baro-ventilatory reflex.

Animals↗

PubMed1989

Performance of the human vestibuloocular reflex during locomotion.

1. The stability of gaze was measured in nine normal subjects during 30-s epochs of standing, walking in place, and running in place. The angle of gaze and head rotations in horizontal and vertical planes were measured using the magnetic search coil technique. Subjects visually fixed on a stationary object located at a distance of 100 m; thus measurements of gaze indicated the stability of images on the retina. 2. During standing, walking, or running in place, the standard deviation of the angle of gaze was less than 0.4 degrees, both horizontally and vertically. During standing and walking in place, peak gaze velocity (Gp) was less than 3.0 degrees/s. During running in place, Gp was less than 3.0 degrees/s horizontally but ranged up to 9.3 degrees/s vertically. 3. Visual acuity was measured during standing, walking, and running in place. During walking in place, five of nine subjects showed a small but significant (P = 0.03) decline in visual acuity compared with standing. During running in place, all nine subjects showed a small but significant (P = 0.002) decline in visual acuity compared with standing. 4. Stability of gaze was also measured during vigorous, voluntary head rotations in the horizontal (yaw) or vertical (pitch) planes, for 15-s epochs. Gp ranged as high as 70 degrees/s horizontally and 41 degrees/s vertically. All subjects reported illusory movement of the seen environment during these head rotations. 5. The suitability of linear systems techniques for analysis of the horizontal and vertical vestibuloocular reflex (VOR) during walking and running in place was assessed using coherence spectral analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1988

CO2 control of the respiratory system: plant dynamics and stability analysis.

A stability analysis of respiratory chemical control is developed using a mathematical model of CO2 mass transport dynamics. Starting with a 3-compartment model of CO2 stores that distinguishes alveolar, muscle, and other tissue, model reduction techniques are applied to obtain a first-order representation of the respiratory plant. This model contains an effective tissue volume for CO2, whose derived value is much smaller than previously predicted. To investigate oscillatory instabilities, a controller which incorporates only peripheral chemoreceptor responses was added to the first-order plant model. An explicit stability index (SI) is obtained analytically from a linearized version of this model. SI varies directly with the controller gain and circulation delay time and inversely with the effective tissue volume and inspired CO2 concentration. Numerical simulations using the first-order nonlinear model show that SI is a good predictor of system stability. According to the linearized model, the system is stable for SI less than 1; from the nonlinear model, the system is stable for SI less than 1.1. For typical normal adults, the SI value is well within the stable region.

Adult↗