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Biomedical subjects

D T Frazier

Publications and source records attributed to D T Frazier.

At least 55 records · Page 3Linked to original sources
PubMed1985

Chemosensitivity of crayfish slowly adapting stretch receptors to nicotine.

It has recently been demonstrated that slowly adapting stretch receptors (SASRs) in the airways of the dog respond directly to nicotine (Federation Proc. 43: 318, 1984). The purpose of the present experiment was to investigate this chemical effect on an isolated stretch receptor. The crayfish muscle receptor organ was chosen, since crayfish muscle is reported to be insensitive to nicotine or acetylcholine and therefore permits the testing of any direct chemical effect of nicotine on the muscle stretch receptors. The tail was removed and pinned out in a tissue bath, and a stretch receptor organ was surgically isolated. Single-unit SASR extracellular nerve recordings were made while simultaneously measuring tension in the tail. Drugs were prepared in Van Harreveld's solution and administered into the bath kept at 18 degrees C. When resting muscle tension was essentially reduced to zero by cutting both ends of the receptor organ muscle, nicotine (0.07 microM) added to the bath increased receptor activity fourfold. This response was abolished by treatment with hexamethonium (690 microM). In a second group of animals in which the muscle was left intact, nicotine was shown to significantly increase receptor sensitivity to step changes in muscle tension. Once again hexamethonium blocked the response to nicotine. These results demonstrate that the sensitivity of mechanoreceptor can be altered by chemical interaction with nicotinic receptors, which dramatically alter sensory receptor activity.

Animals↗
PubMed1984

Effects of bronchoconstriction on breathing during normoxia and hypoxia in anesthetized cats.

The effect of an increase in bronchomotor tone on control of breathing during both normoxia and hypoxia, and the role of vagal afferents in regulating these responses were studied in 15 anesthetized cats. Minute ventilation (VE) was measured with a pneumotachograph connected in series with a tracheal cannula. Total diaphragmatic EMG activity per minute (means p X f, peak EMG moving average X respiratory frequency) was measured to assess the central inspiratory drive. Bronchoconstriction was generated by inhalation of methacholine aerosol (10-30 breaths, 0.5% solution) which increased total lung resistance to approximately 400% of the control value. Transient hypoxia was induced by allowing the cats to rebreathe a hypoxic gas mixture (4.5% O2 balanced N2) for approximately 1 min. During normoxia, bronchoconstriction increased VE from a baseline of 100 to 129 +/- 7% (mean +/- SEM; P less than 0.05) and increased (means p X f) from 100 to 174 +/- 16% (P less than 0.01). During hypoxia, the response of (means p X f) to bronchoconstriction (404 +/- 40%) was still greater than without bronchoconstriction (306 +/- 35%; P less than 0.01), but the responses of VE were not significantly different between these two conditions (P greater than 0.05). After sectioning both vagus nerves the bronchoconstriction-induced increase in central inspiratory drive was either reduced (during normoxia) or abolished (during hypoxia). These results suggest that stimulation of vagal bronchopulmonary afferents are involved in regulating the ventilatory responses to bronchoconstriction. Other non-vagal factors, such as intrinsic properties and reflex responses of the respiratory muscles, may also contribute, in part, to the observed responses.

Anesthesia↗
PubMed1984

Respiratory volume-timing relationship during sustained elevation of functional residual capacity.

In 7 spontaneously breathing dial-urethane anesthetized cats a negative pressure was produced around the thorax and abdomen to increase the functional residual capacity (FRC) by about 1 tidal volume for up to 60 min. A tracheal cannula was connected to a resistive manifold for selective loading of inspiration or expiration. Two resistive loads and tracheal occlusion were presented six times each at control FRC (FRCc), after 60 min at elevated FRC (FRCe) and 30 min after return to FRCc. Inspiratory and expiratory durations (TI and TE) were measured from diaphragmatic EMG. We observed that TI at FRCe (0.88 +/- 0.11 sec) was not significantly shorter than TI at FRCc (1.06 +/- 0.14 sec). Tracheal occlusion at FRCe caused a shorter TI (1.37 +/- 0.15 sec) than at FRCc (1.79 +/- 0.21 sec) (P less than 0.05). The slope (m) of the VI-TI relationship generated by the resistive loads at FRCe was steeper (m = -65 +/- 7 ml X sec-1) and shifted upward from the VI-TI curve at FRCc (-50 +/- 6 ml X sec-1) (P less than 0.05). The VE-TE relationship at FRCe was not significantly changed from control. Thirty minutes following return to FRCc, TI was still slightly shorter (0.96 +/- 0.11 sec) than the initial TI at FRCc. We conclude: (1) The slope of the VI-TI relationship is determined to a great extent by the total lung volume. However, under the conditions of sustained elevation of FRC, this relationship is influenced by the partial adaptation of slowly adapting pulmonary receptors SARs. (2) The increased SAR activity at end expiration during FRCe may not influence the control of TE.

Animals↗
PubMed1983

Response of pulmonary stretch receptors to shifts of functional residual capacity.

The response of slowly adapting pulmonary stretch receptors (PSRs) to sustained elevations of functional residual capacity (FRC) was investigated in spontaneous breathing anesthetized cats. A subatmospheric pressure was produced around the thorax and abdomen to increase FRC by approximately one tidal volume (VT) for up to 60 min. During eupneic breathing the PSR frequency (fPSR) was closely related to changes in transpulmonary pressure (PTP), but occasionally hysteresis was observed in the FPSR - PTP relationship. Elevation of FRC caused most phasic PSRs to discharge continuously for a few breaths before returning to a phasic discharge pattern. During the shift in FRC there were increases in mean fPSR, peak fPSR firing threshold which were sustained throughout the period of elevated FRC. PSRs that normally showed discharges at FRC similarly increased their mean and peak firing rates. For all PSRs the y-intercept (fPSR at PTP = 0) of the fPSR - PTP relationship was decreased but the sensitivity of the PSR as defined by delta fPSR/delta PTP was not changed until the period of elevated FRC exceeded 30 min. Thereafter, PSR sensitivity tended to decline. These results suggest that PSRs undergo some modification of their discharge parameters during prolonged elevation of FRC.

Action Potentials↗
PubMed1983

Response of ventral respiratory group inspiratory neurons to mechanical loading.

The bursting patterns of 32 ventral respiratory group (VRG) medullary inspiratory neurons were studied in response to selected mechanical loads in 68 allobarbital-urethan-anesthetized cats. Mechanical loads consisted of three levels of resistive loads, one elastic load, and tracheal occlusion (TO). The application of each load was manipulated to oppose either inspiration or expiration. Loads were applied for only one inspiration or expiration to prevent changes in chemical drive. All loaded breath unit responses were analyzed and compared with control values for inspiratory time (TI), expiratory time (TE), spikes per burst (SPB), and average firing rate (FR). Inspiratory mechanical loads resulted in statistically significant increases in TI and SPB but only small nonsignificant increases in FR and TE. Expiratory resistive loading produced its predominant effect on TE. The higher expiratory mechanical loads also caused significant increases in the subsequent unloaded TI and SPB. In contrast to expiratory loading, large inspiratory loads did not significantly affect the next unloaded TE. Bilateral cervical vagotomy eliminated the observed neural responses to loading for both inspiratory and expiratory loads. All of the 71 neurons tested with lung inflations and TO at end inspiration showed inhibition (Ra type) rather than facilitation (R beta).

Animals↗
PubMed1983

Reflex control of breathing following inhalation of cigarette smoke in conscious dogs.

The acute ventilatory response to spontaneously inhaled cigarette smoke (750 ml, 10% concentration) was studied in 92 experiments on 6 awake resting dogs. Upon the first or second breath of smoke inhalation, either an apnea or an augmented breath was elicited consistently in each dog, and a hyperpnea occurred subsequently. Minute ventilation (VE) increased from a base line of 3.2 to a peak of 23.9 l/min at 8.3 s (mean values) after the smoke was completely inhaled and returned toward base line in 1-3 min. Cold blocking of both vagi (exteriorized in skin loops) eliminated the initial change in breathing pattern but did not significantly reduce the delayed hyperpnea. Denervation of carotid body chemoreceptors alone abolished 71.5% of the increase in VE induced by cigarette smoke. These results suggest that the apnea or augmented breath immediately following the smoke inhalation is mediated through vagal afferents, whereas the delayed hyperpnea results primarily from the stimulation of carotid body chemoreceptors, presumably by the absorbed nicotine.

Animals↗
PubMed1982

Effects of L-glutamate and GABA on the response of expiratory neurons to mechanical loads.

Expiratory neurons in the area of the nucleus retroambigualis were studied in anesthetized cats to determine their responsiveness to the iontophoretic application of the putative neurotransmitters, glutamate and gamma-aminobutyric acid (GABA). Previous studies with glutamate and GABA revealed that these two substances were very effective in modulating the spontaneous activity of phasic medullary respiratory neurons. Mechanical loading of expiration, both resistive and elastic, was employed to test whether the presence of these transmitter substances altered the sensitivity of the expiratory cell to its volume related vagal input. Expiratory unit activity analysis included: spikes/burst, burst duration, and average firing rate. Addition of mechanical loads on expiration caused consistent increases in all parameters monitored. Iontophoretically applied glutamate (means = 65 nA) resulted in modest increases in all parameters. When mechanical loads were applied in the presence of a sustained level of glutamate the effects were additive. The general shape of the firing profile observed with loading remained essentially unchanged. Application of GABA (means = 46 nA) resulted in a significant decrease in the parameters monitored. However, as long as phasic activity remained, loads applied in the presence of GABA produced approximately the same absolute change as they did during control. Some cells exposed to high concentrations of GABA lost their phasic activity. This study suggests that either the synaptically activated receptors are not affected by glutamate or that these particular sites are not accessible via iontophoretic application. GABA depressed the activity of the cells in a graded fashion, but in modest concentrations did not interfere with the overall effectiveness of the vagally mediated input.

Action Potentials↗
PubMed1982

The effect of transmitter antagonists on phasic respiratory neurons.

The activity of inspiratory neurons in the nucleus tractus solitarius (NTS) and of expiratory neurons in the nucleus retroambigualis (RNA) was recorded during the iontophoresis of L-glutamate, bicuculline, and strychnine in chloralose-urethane-anesthetized cat. Bicuculline methoxide caused increased activity of NTS and NRA neurons during their active or burst phases. Neither bicuculline nor strychnine caused increased activity during the silent phases of NTS or NRA neurons. When neurons were driven to fire during their silent phase by L-glutamate, the application of bicuculline methoxide caused a diminution of the evoked activity. It is concluded that both inspiratory and expiratory neurons receive inhibitory inputs during both their active and silent phases. Gamma-aminobutyric acid appears to be gating both the excitatory and inhibitory information to NTS and NRA neurons. Strychnine was generally ineffective in changing the firing patterns of inspiratory and expiratory neurons suggesting a limited role of glycine, taurine, and L-alanine in the respiratory network.

Animals↗
PubMed1981

The effect of the resistive loading of inspiration and expiration on pulmonary stretch receptor discharge.

Anesthetized, spontaneously breathing cats were used to examine the hypothesized role of slowly adapting pulmonary stretch receptors (PSR) in the control of breath duration. Initially, graded inspiratory and expiratory resistive loads were added to elucidate the inspiratory and expiratory volume-time relationship with both vagi intact. Unilateral vagotomy increased the slope of the VI--TI relationship indicating a reduction of the volume related modulation of TI. PSR frequency (fPSR) at end-inspiration also progressively decreased resulting in a fPSR--TI relationship qualitatively similar to the VI--TI curve. Expiratory resistive loading also produced an increased slope for the VE--TE relationship when the right vagus nerve was severed. The prolongation of TE was associated with a progressive increase in the number of PSR discharges during the loaded expiration. These results support the hypothesized role of PSR in the vagally mediated prolongation of TI and TE during resistive loading. In a subsequent series of experiments, the changes in fPSR were correlated with the tidal volume and transpulmonary pressure (PTP) changes. The fPSR was linearly related to PTP during both eupnic and loaded breathing. When fPSR was plotted against volume, a clockwise hysteresis was observed. These results suggest that in the spontaneously breathing cat, intrathoracic PSR frequency varies as a function of the transmural pressure across the airways.

Animals↗
PubMed1981

Effect of bronchoconstriction on the firing behavior of pulmonary stretch receptors.

To study the effect of bronchoconstriction on the activity of pulmonary stretch receptors (PSRs), acetylcholine aerosols (0.05% solution) were delivered continuously into the lungs while the afferent activity of a single PSR was recorded from a filament of the vagus nerve. The relationship between the PSR frequency (fPSR) and the transpulmonary pressure (Ptp) was examined during both constant volume ventilation and hyperinflation. During bronchoconstriction, the peak fPSR for the same tidal volume increased significantly (P less than 0.05) compared to the control response obtained with saline aerosols. However, the fPSR at functional residual capacity decreased in the receptors above the carina but increased in those below. Bronchoconstriction induced a hysteresis in the dynamic Ptp-fPSR relationship during hyperinflation in 11 out of the 21 receptors studied: a clockwise hysteresis was found in those receptors above the carina whereas a counterclockwise one in those below. Results of these studies suggest that the response of PSRs to bronchoconstriction depends on their locations in the tracheobronchial tree.

Acetylcholine↗
PubMed1979

Behavior of expiratory neurons in response to mechanical and chemical loading.

The response of medullary expiratory neurons to added mechanical and chemical loads was studied in anesthetized cats. Alterations in burst characteristics and central timing were compared in the intact and bilaterally vagotomized cat. The following results were obtained: (1) Graded expiratory airflow resistances caused progressive increases in burst duration, spikes per burst and firing rate; similar effects were noted for end-inspiratory tracheal occlusions and continuous positive breathing; all facilitation was eliminated by vagotomy. (2) Graded inspiratory airflow resistances delayed the onset of an expiratory burst but did not change the overall burst characteristics. (3) Acute hypercapnia increased ventilation without noticeable changes in expiratory burst characteristics; acute hypoxia produced a reduction in burst duration concomitant with changes in ventilation. It is concluded that (1) expiratory neurons are responsive to vagally mediated volume information and (2) transient hypoxia and hypercapnia sufficient to increase ventilation does not increase the firing rate of expiratory neurons but exerts differential effects with respect to timing. It is suggested that expiratory duration is related to the time integral of expired volume and that the increase in FRC imposed by expiratory loads does not alter the central timing of the next inspiration.

Action Potentials↗
PubMed1976

Respiratory volume-time relationships during resistive loading in the cat.

The first-breath (neural) effects of graded resistive loads added separately during inspiration and expiration was studied in seven anesthetized cats before and after bilateral vagotomy. Additions of airflow resistance during inspiration reduced the volume inspired (VI) and increased inspiratory duration (TI). The duration of the ensuing unloaded expiration (TE) was unchanged. Vagotomy eliminated the TI modulation with inspiratory loads. Tracheal occlusion at the onset of inspiration yielded TI values similar to the fixed values observed following vagotomy. Resistive loads added during expiration produced similar results. Expired volume (VE) decreased and (TE) increased approaching the values obtained after vagotomy. Unlike the inspiratory resistive loads, loading during expiration results in an upward shift in the functional residual capacity (FRC). The FRC shift produces a time lag between the onset of diaphragmatic (EMG) activity and the initiation of airflow of the next (unloaded) inspiration. These studies suggest separate volume-time relationships for the inspiratory and expiratory phases of the breathing cycle. Both relationships are dependent upon vagally mediated volume feedback.

Airway Resistance↗
PubMed1976

Effects of calcium on the local anesthetic suppression of ionic conductances in squid axon membranes.

The effects of varying the external calcium concentration on the suppression of membrane ionic conductances by procaine and benzocaine have been examined under voltage-clamped conditions. The suppression of peak conductance and steady-state conductance by procaine or benzocaine applied externally or internally was not affected by changing the external calcium concentration between 10 and 100 mM. When the calcium concentration was lowered below 10 mM (5 or 2 mM), the procaine effect was slightly potentiated. This augmentation could not be ascribed to an acceleration in the rate of penetration of procaine into the axon in low calcium solutions. The resting membrane conductance was slightly decreased by procaine in a manner independent of the external calcium concentration. The maximum effect of procaine on resting conductances was obtained at a concentration much lower than that required for maximum suppression of peak and steady-state conductances. The present results are not compatible with the hypothesis that calcium competes with local anesthetics for a negatively charged site on the membrane. It is suggested that hydrophobic interactions of local anesthetic molecules with the membrane affect the resting membrane conductance whereas coulombic interactions are responsible for the conductance changes observed during nerve activity.

Anesthetics, Local↗
PubMed1975

Comparison of the action of different barbiturates on squid axon membranes.

Experiments utilizing squid giant axons have been carried out to determine if the duration of anesthesia obtained from phenobarbital, pentobarbital and hexobarbital can be explained by events related to their action at the nerve membrane level. For comparison, the barbiturates were perfused both outside and inside the squid axon at concentrations which produced an approximately equivalent depression of the maximum rate of rise of the action potential. The time to 50% maximum block and the time to 50% maximum recovery following washing, were compared for all three drugs. All three barbiturates were more potent from inside the squid axon than from the outside. This finding coupled with the fact that the time course of the drug effects was much shorter when applied inside as compared to outside suggests an internal site of action. There was no statistically significant difference between a short acting barbiturate and a long acting barbiturate with respect to their time course of action or recovery when they were both applied to either the inside or outside of the membrane.

Action Potentials↗
PubMed1975

Site of action and active form of procaine in squid giant axons.

The active form of procaine and its, site of action on the nerve membrane have been studied in intact and internally perfused squid giant axons. Voltage clamp techniques were employed to measure the masimum values for peak sodium conductance and for steady-state potassium conductance as an index of activity. Changes in internal pH between 7 and 8 do not influence the blocking potency of procaine applied internally. This result, when compared to theoretical curves, is only compatible with the notion that the charged form of procaine present inside is the active form. If one momentarily arrests internal perfusion during an experiment in which procaine is being applied externally, the conductance block is significantly potentiated. When procaine is applied simultaneously to both external and internal phases, most of the block can be reversed by washing out the inside at a time when the outside is still being perfused with procaine. If one reverses this procedure, very little recovery is noted with removal of procaine from the external phase. The rate of recovery from the procaine blockage is much faster in internally perfused axons. These three observations support the notion that procaine acts from inside the nerve membranes. It is concluded that procaine, as other lidocaine derivatives studied previously, acts from the internal nerve membrane surface in the charged form.

Animals↗