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Biomedical subjects

T E Dick

Publications and source records attributed to T E Dick.

At least 19 recordsLinked to original sources
PubMed2004

Modeling the ponto-medullary respiratory network.

The generation and shaping of the respiratory motor pattern are performed in the lower brainstem and involve neuronal interactions within the medulla and between the medulla and pons. A computational model of the ponto-medullary respiratory network has been developed by incorporating existing experimental data on the medullary neural circuits and possible interactions between the medulla and pons. The model reproduces a number of experimental findings concerning alterations of the respiratory pattern following various perturbations/stimulations applied to the pons and pulmonary afferents. The results of modeling support the concept that eupneic respiratory rhythm generation requires contribution of the pons whereas a gasping-like rhythm (and the rhythm observed in vitro) may be generated within the medulla and involve pacemaker-driven mechanisms localized within the medullary pre-Botzinger Complex. The model and experimental data described support the concept that during eupnea the respiration-related pontine structures control the medullary network mechanisms for respiratory phase transitions, suppress the intrinsic pacemaker-driven oscillations in the pre-BotC and provide inspiration-inhibitory and expiration-facilitatory reflexes which are independent of the pulmonary Hering-Breuer reflex but operate through the same medullary phase switching circuits.

Animals↗
PubMed2003

Invited review: Neural network plasticity in respiratory control.

Respiratory network plasticity is a modification in respiratory control that persists longer than the stimuli that evoke it or that changes the behavior produced by the network. Different durations and patterns of hypoxia can induce different types of respiratory memories. Lateral pontine neurons are required for decreases in respiratory frequency that follow brief hypoxia. Changes in synchrony and firing rates of ventrolateral and midline medullary neurons may contribute to the long-term facilitation of breathing after brief intermittent hypoxia. Long-term changes in central respiratory motor control may occur after spinal cord injury, and the brain stem network implicated in the production of the respiratory rhythm could be reconfigured to produce the cough motor pattern. Preliminary analysis suggests that elements of brain stem respiratory neural networks respond differently to hypoxia and hypercapnia and interact with areas involved in cardiovascular control. Plasticity or alterations in these networks may contribute to the chronic upregulation of sympathetic nerve activity and hypertension in sleep apnea syndrome and may also be involved in sudden infant death syndrome.

Animals↗
PubMed2001

Incorporating inheritance into models for understanding ventilatory behavior.

Ventilation and its components (frequency and tidal volume) appear to be determined to a significant extent by inheritance. Gene manipulation, gene identification, and functional genomics now offer powerful tools to identify the strength and mode of inheritance for ventilatory behavior under steady-state and non-steady-state conditions, in health and in disease. Conscious integration of genetic principles into existing explanatory models may increase the likelihood of detecting traits that correlate with protein systems responsible for the structures and the functional components of respiration.

Humans↗
PubMed2001

Heterogeneity within geniohyoid motor unit subpopulations in firing patterns during breathing.

Respiratory motor units (MU) segregate into subpopulations, which differ in firing patterns during resting and stimulated breathing. For phrenic/diaphragm MUs, diversity also exists within subpopulations, and is greater for late than early-onset MUs. The present study characterized the extent of diversity within upper airway respiratory MU subpopulations by recording geniohyoid MUs in anesthetized cats. Inspiratory MUs (I-MU, n=21) had a wide range of firing durations (coefficient of variation (CV)=42%). In contrast, inspiratory-expiratory MUs (I/E-MU, n=19) had a narrow range of firing durations during inspiration (CV=13%), but a wide range of firing durations during expiration (CV=36%). Mean firing frequency had similar degrees of diversity among units for I-MU and I/E-MU (CV=31-40%). For I-MU firing duration correlated with mean firing frequency, whereas no such relationship was apparent for I/E-MU. Single-breath end-expiratory airway occlusion decreased heterogeneity in firing duration during inspiration and increased it during expiration, whereas end-inspiratory airway occlusion decreased heterogeneity during expiration. In conclusion, (a) there is considerable diversity within geniohyoid MU subpopulations receiving respiratory drive; (b) the degree of diversity within subpopulations differs for I-MU and I/E-MU; and (c) diversity within subpopulations in timing of activity is modulated by single-breath airway occlusion.

Airway Obstruction↗
PubMed2001

Modulation of diaphragm action potentials by K(+) channel blockers.

K(+) channels regulate diaphragm contractility. The present study examined the electrophysiological mechanisms accounting for diversity among K(+) channel blockers in their inotropic actions on the diaphragm. Rat diaphragmatic muscle fibers were recorded intracellularly in vitro at 37 degrees C. Apamin and charybdotoxin (Ca2+)-activated K(+) channel blockers) did not alter resting membrane potential or action potentials. Glibenclamide (ATP-sensitive K(+) channel blocker) slowed action potential repolarization by 12% (P<0.05) and increased action potential area by 25% (P<0.005). Tetraethylammonium (which blocks several types of K(+) channels) increased action potential overshoot by 20% (P<0.01) and prolonged action potential rise time by 17% (P<0.02). 4-Aminopyridine and 3,4-diaminopyridine (which also block several types of K(+) channels) slowed action potential repolarization by 163% (P<0.0001) and 253% (P<0.0001), and increased action potential area by 183% (P<0.0001) and 298% (P<0.0001), respectively. Slowing of repolarization for the aminopyridines was especially marked at voltages approaching resting membrane potential, thereby changing action potential repolarization from a first to a second order decay. Previously reported variability in inotropic effects among K(+) channel blockers correlated significantly with the extent to which they slowed action potential repolarization and increased action potential area, but not with changes in other action potential properties.

Action Potentials↗
PubMed2001

Ventilatory behavior after hypoxia in C57BL/6J and A/J mice.

Given the environmental forcing by extremes in hypoxia-reoxygenation, there might be no genetic effect on posthypoxic short-term potentiation of ventilation. Minute ventilation (VE), respiratory frequency (f), tidal volume (VT), and the airway resistance during chemical loading were assessed in unanesthetized unrestrained C57BL/6J (B6) and A/J mice using whole body plethysmography. Static pressure-volume curves were also performed. In 12 males for each strain, after 5 min of 8% O2 exposure, B6 mice had a prominent decrease in VE on reoxygenation with either air (-11%) or 100% O2 (-20%), due to the decline of f. In contrast, A/J animals had no ventilatory undershoot or f decline. After 5 min of 3% CO2-10% O2 exposure, B6 exhibited significant decrease in VE (-28.4 vs. -38.7%, air vs. 100% O2) and f (-13.8 vs. -22.3%, air vs. 100% O2) during reoxygenation with both air and 100% O2; however, A/J mice showed significant increase in VE (+116%) and f (+62.2%) during air reoxygenation and significant increase in VE (+68.2%) during 100% O2 reoxygenation. There were no strain differences in dynamic airway resistance during gas challenges or in steady-state total respiratory compliance measured postmortem. Strain differences in ventilatory responses to reoxygenation indicate that genetic mechanisms strongly influence posthypoxic ventilatory behavior.

Airway Resistance↗
PubMed2000

Ventrolateral pons mediates short-term depression of respiratory frequency after brief hypoxia.

The respiratory response to hypoxia is dynamic in the adult anesthetized Sprague-Dawley rat. Hypoxia elicits acute increases in both tidal volume (VT) and respiratory frequency (fR) followed by short-term increases in VT and short-term decreases in fR. After brief hypoxia (<1 min), recovery of the breathing pattern is again dynamic, where both VT and fR decrease immediately, but where VT remains above, and fR drops below, baseline. These acute changes are followed by a short-term progressive decrease in VT and increase in fR to baseline. We have identified a potential neural mechanism that depends on the integrity of the ventrolateral (vl) pons. Our studies show that: (a) blockade of activity in the vl pons prevents the short-term decrease in fR after hypoxia (b) stimulation of the vl pons decreases fR, and (c) vl pontine expiratory neurons are activated after hypoxia. These neurons may not be acting through alpha(2) -adrenergic receptors, but their effect does depend on NMDA-type receptor function. We conclude that the vl pons is a critical element in the pontomedullary network that generates and modulates the fR response to acute hypoxia.

Animals↗
PubMed1998

Post-hypoxic frequency decline does not depend on alpha2-adrenergic receptors in the adult rat.

The aim of this study was to determine whether post-hypoxic frequency decline (PHFD) requires central activation of alpha2-adrenergic receptors. PHFD is defined as the undershoot in respiratory frequency that occurs immediately following brief hypoxic periods. Adult anesthetized, vagotomized rats were exposed to hypoxia (8% O2, mean=45 s) before and after intracerebroventricular (i.c.v.) infusion of vehicle or alpha2-antagonist. The efficacy of the i.c.v. antagonist was assessed by recording the response to intravenous injection of alpha2-agonist before and after the infusion. We compared breathing frequencies before, during, and after hypoxia, both before and after treatments. The decline in breathing frequency after hypoxia was not prevented by the alpha2-antagonists, RX 821002 or SK&F-86466. Guanabenz, an alpha2-agonist, prolonged baseline expiration and potentiated PHFD. Prior treatment with SK&F-86466 blocked the agonist-evoked response which was also reversed by subsequent administration of SK&F-86466. We conclude that PHFD does not require the activation of alpha2-adrenergic receptors, but that alpha2-adrenergic receptors can modulate resting and post-hypoxic respiratory frequency.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1998

Persistence of the biphasic ventilatory response to hypoxia in preterm infants.

OBJECTIVE: To characterize postnatal maturation of the biphasic ventilatory response to hypoxia in order to determine whether it persists beyond the first weeks of life in preterm infants, and the contributions of respiratory frequency and tidal volume to this response. METHODS: Stable preterm infants were studied at two postnatal ages, 2 to 3 weeks (n = 12) and 4 to 8 weeks (n = 12), before hospital discharge at 35 weeks (range, 33 to 38 weeks) of postconceptional age. Infants were exposed to 5 minutes of 15% (or 13%) inspired oxygen; ventilation, oxygen saturation, end-tidal partial pressure of carbon dioxide, and heart rate were simultaneously recorded. RESULTS: Minute ventilation exhibited a characteristic biphasic response to hypoxia at both postnatal ages, regardless of the development of periodic breathing. At both ages there was a transient increase in tidal volume, which peaked at 1 minute, accompanied by a sustained decrease in respiratory frequency as a result of significant prolongation of expiratory time. CONCLUSION: The characteristic biphasic ventilatory response to hypoxia persists into the second month of postnatal life in preterm infants. We speculate that this finding is consistent with the prolonged vulnerability of such infants to neonatal apnea.

Apnea↗
PubMed1998

A role for NMDA receptors in posthypoxic frequency decline in the rat.

Posthypoxic frequency decline (PHFD) refers to the undershoot in respiratory frequency that follows brief hypoxic exposures. Lateral pontine neurons are required for PHFD. The neurotransmitters involved in the circuit that activate and/or are released by these pontine neurons regulating PHFD are unknown. We hypothesized that N-methyl-D-aspartate (NMDA) receptors are required for PHFD, because of the similarity in respiratory pattern after blocking lateral pontine activity or NMDA receptors. Furthermore, we hypothesized that the location of these NMDA receptors could be visualized by optimizing binding affinity with spermidine. In vagotomized, anesthetized rats (n = 16), cardiorespiratory responses to hypoxia (8% O2, 30-90 s) were recorded before and after dizocilpine (10 microg-1 mg/kg iv), and NMDA receptors were mapped with [3H]dizocilpine (n = 6). Dizocilpine elicited a dose-related effect on PHFD, blocking PHFD at high doses. Resting arterial blood pressure and breathing frequency decreased with high doses of dizocilpine, but the respiratory response to hypoxia remained intact. Our novel anatomical data indicate that NMDA receptors were widespread but distributed differentially in the brain stem. We conclude that NMDA receptors are located in pontine and medullary respiratory-related regions and that PHFD requires NMDA-receptor activation.

Animals↗
PubMed1997

Prolongation in expiration evoked from ventrolateral pons of adult rats.

Activation of neurons in the ventrolateral (vl) pons was hypothesized to alter the breathing pattern because previous studies demonstrated apneusis after inhibiting neuronal activity with bilateral muscimol (10 mM) microinjections into the vl pons (17). The excitatory amino acid L-glutamate (10 mM) was microinjected (10-100 nl) into the vl pons in anesthetized, vagotomized, paralyzed, and ventilated adult rats (n = 8). In four of these animals, the target site was approached from the ventral surface of the pons to avoid penetrating the dorsolateral (dl) pons. The expiratory phase was prolonged transiently and concurrently with the microinjection. The location of the injection sites included the A5 area, was independent of the approach, and was distinct from the dl pons. These results complement our previous data and indicate that neurons located in the vl pons influence respiration specifically by prolonging expiration when activated and by delaying the inspiratory-to-expiratory phase transition when inhibited.

Animals↗
PubMed1997

The role of pulmonary stretch receptor activation during cough in dogs.

The role of pulmonary stretch receptors in the modulation of expiratory muscle activity during cough is controversial. To evaluate their potential influence on expiratory effort during cough, we compared expiratory muscle activity during unobstructed cough to that during obstructed cough in which the trachea was occluded at the end-inspiration and maintained throughout the subsequent expiration. Cough was evoked by mechanical stimulation of the intrathoracic trachea in 9 anesthetized, tracheotomized dogs. Peak triangularis sterni (TS), internal intercostal (IIC) and transversus abdominis (TA) muscle EMG were monitored to assess both rib cage and abdominal muscle activation during expiration. During cough, expiratory activity increased and peak activity shifted from Stage II to Stage I expiration. Peak expiratory muscle activation during unobstructed and occluded coughs were not significantly different: during unobstructed coughs, peak EMG's (mean +/- SE as percent of resting breathing) were TS, 212 +/- 18; IIC, 425 +/- 72; TA, 406 +/- 66; and during obstructed cough: TS, 188 +/- 24; IIC, 365 +/- 44; TA, 387 +/- 77 (n = 9). These data indicate that enhanced vagal stimulation resulting from airway occlusion does not affect expiratory activity during cough. We suggest that during cough, the expiratory muscles are activated in a stereotypical pattern by the neural network generating the cough and this pattern of activation is not affected by phasic vagal input.

Animals↗
PubMed1996

Neurones in the ventrolateral pons are required for post-hypoxic frequency decline in rats.

1. The breathing pattern following acute hypoxia (arterial O2 pressure (Pa,O2), 27.4 +/- 7.7 mmHg) was measured in intact, anaesthetized and spontaneously breathing adult rats (n = 4) and in anaesthetized, vagotomized, paralysed and ventilated animals (n = 14). Measurements were made both before and after bilateral lesions or chemical inactivation of neurones in the lateral pons. Respiratory motor activity was recorded as an index of the respiratory cycle. We tested the hypothesis that the ventrolateral pons is required for expression of post-hypoxic frequency decline, defined as a decrease in respiratory frequency below steady-state baseline levels following brief exposures to hypoxia. 2. We identified an area in the ventrolateral pons where brief (1 ms) low current (< or = 20 microA) pulses evoked a short-latency inhibitor of phrenic nerve activity. At this site, bilateral electrical or chemical lesions (n = 3) were performed, or neural activity was inhibited by focal injections of 10 mM muscimol (n = 9). In six control animals, neural activity was inhibited by muscimol injections into the lateral pons, dorsal to the target site. 3. Prior to pontine intervention, respiratory frequency decreased below baseline levels following 20-110 s of 8% O2. The decrease in frequency resulted from a prolongation of expiration (up to 276%), which gradually returned to baseline levels (tau = 45 s). 4. Following lesions or inhibition of neural activity in the ventrolateral pons, baseline inspiratory (TI) and expiratory (TE) durations were altered, albeit minimally, in the animals with intact vagus nerves. Expiratory duration following hypoxia was not different from baseline levels either in vagotomized (P = 0.18) or intact (P > 0.05) animals. In contrast, injections of muscimol at more dorsal sites did not alter the decrease in frequency normally seen following hypoxia. 5. Histological examination revealed that effective lesion or injection sites were within the lateral pontine tegmental field and included portions of the noradrenergic A5 cell group. 6. We conclude that the mechanism responsible for post-hypoxic frequency decline involves an active neural process that depends on the integrity of the ventrolateral pons.

Animals↗
PubMed1996

Respiratory responses to tracheobronchial stimulation during sleep and wakefulness in the adult cat.

The response to tracheal stimulation (50 microliters of tap water) during wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep was investigated in adult cats. In wakefulness, repetitive coughing occurred on 80% of the trials. In NREM and REM sleep, the most frequent response (approximately 69% and 58% of the trials, respectively) was arousal, followed by coughing. Apneas occurred following the stimulus and before arousal in 11% and 24% of the trials in NREM and REM sleep, respectively. In NREM sleep, the tracheal stimulus sometimes evoked expiratory efforts following a normal inspiratory effort (11% of the trials). These were much weaker than the expiratory efforts during coughing in wakefulness. In REM sleep, stimulation in 11% of the trials elicited increased inspiratory efforts. Although these may have been diminutive preparatory inspirations for coughing, they were much smaller than preparatory inspirations associated with coughing in wakefulness, and they were never followed by active expiratory efforts. Arousal from either NREM or REM sleep in response to tracheal stimulation was sometimes associated with an augmented breath. This response, which is common upon spontaneous arousal, may lead to deeper aspiration of the tracheal fluid. We conclude that in cats coughing requires wakefulness and that airway stimuli in sleep cause a variety of respiratory responses, some of which may be maladaptive.

Animals↗