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Biomedical subjects

C L Webber

Publications and source records attributed to C L Webber.

32 records · Page 2Linked to original sources

Baroreceptor modulation of inspiratory termination by intercostal nerve stimulation.

The influence of carotid sinus baroreceptor activity on the termination of inspiration by intercostal nerve stimulation was assessed in decerebrate cats which were paralyzed, artificially ventilated and bilaterally vagotomized. The carotid sinus was vascularly isolated bilaterally so that carotid sinus pressure could be precisely controlled independent of the systemic arterial pressure. Inspiratory activity was monitored by a phrenic neurogram. The threshold current at which electrical stimulation of the T6 intercostal nerve terminated phrenic neural activity was determined by stimulating the T6 intercostal nerve at 10 different delays from the onset of phrenic discharge. An increase in mean carotid sinus pressure from 100 to 150 mm Hg decreased the threshold current required to terminate inspiration at each delay. Similarly, a decrease in mean carotid sinus pressure from 100 to 50 mm Hg increased the threshold current. Alteration of the systemic arterial pressure (independent of the carotid sinus pressure) by norepinephrine administration did not alter the threshold current. These results demonstrate that alterations in carotid sinus baroreceptor activity have a distinct effect on the mechanisms governing inspiratory termination.

Animals↗

Cerebellar influence on the termination of inspiration by intercostal nerve stimulation.

Stimulation of either the intercostal afferents or the anterior lobe of the cerebellum may terminate inspiratory activity. Since intercostal afferents are known to project to the cerebellum, the present study examined the possibility that this intercostal inhibition of inspiration is mediated through the cerebellum. Decerebrate, vagotomized, paralyzed, and artificially ventilated cats were used. The left T6 intercostal nerve was stimulated centrally with a 3 pulse train (0.1 msec duration, 200 Hz, 0.01-5.0 mA) delivered at 10 different intervals (Ti) after the onset of phrenic neural activity. At each delay the stimulus intensity (mA) was adjusted to the minimal current required to terminate inspiration Plots of mA versus Ti were obtained before and after cerebellectomy at both 4% and 5% end-expiratory CO2 levels. The results demonstrated that the threshold stimulus strength required for inspiratory termination is elevated by hypercapnia. Cerebellectomy, however, did not alter the threshold stimulus strength at either of the CO2 levels. Therefore, although cerebellar inputs may affect the pattern of respiration, this study has shown that the intercostal activation of the inspiratory 'off-switch' is not dependent on an intact cerebellum.

Animals↗

Calculator estimation of cardiac vectors in the frontal plane.

A simple quantitatively method is described that permits the rapid and accurate estimation of frontal plane QRS vector characteristics on an inexpensive programmable calculator. The derived formulas, based upon ECG amplitudes in standard leads I and II, are modified from those of Einthoven and are suitable for all possible angle and magnitude measurements. The accuracy of these measurements was verified in 100 normal human volunteers. Good agreement was found between vector estimates and absolute references describing the frontal plane vector loop. Thus, the estimated vector magnitude closely approximated the maximum instantaneous vector magnitude, and the estimated vector angle closely approximated the mean electrical axis of the heart. The technique compares favorably with other estimation procedures, not sacrificing accuracy for speed of implementation. For this reason, the calculator approach may be of practical interest for routine vector analysis in a clinical setting, including ICUs. All pertinent equations are derived and an example calculator program is provided.

Adolescent↗

Central respiratory drive potentials and membrane potential trajectories in phrenic motoneurons.

Membrane potential trajectories were quantitatively assessed during the burst phase of cat phrenic motoneuron discharges. During burst progression the after-hyperpolarization shifted in the depolarizing direction with little change in spike threshold. Argument is made that these results constitute indirect evidence for the accumulation of potassium ions in the extracellular space of the phrenic motoneuron pool. Functional consequences regarding cell synchronization and recruitment are also discussed.

Action Potentials↗

Time course of intercostal afferent termination of the inspiratory process.

The influence exerted by several somatic nerves on the inspiratory off-switch mechanism has been assessed in decerebrate cats. These animals were paralyzed, artificially ventilated, and bilaterally vagotomized. Inspiratory activity was monitored by a phrenic neurogram. Brief stimulation of either the superficial radical nerve or the sciatic nerve had an inconsistent effect on both the depth of inspiration and the timing of the respiratory cycle. However, stimulation of the T6 intercostal nerve during inspiration elicited a premature phase switch to expiration. Distinct, repeatable thresholds were determined for 10 delays in 100 msec increments after the onset of inspiration. As the delay increased, the threshold current was observed to decrease in all 30 decerebrate cats studied. An increase in the end-expiratory %CO2 caused an elevation of the stimulus threshold. These results correspond to the known characteristics of the inspiratory off-switch. Also, since the intercostal afferents are not normally a major determinant of respiratory rhythmicity in eupnea, this work establishes intercostal nerve stimulation as a very useful technique in the study of inspiratory to expiratory phase switching mechanisms.

Afferent Pathways↗

Experimental Biot periodic breathing in cats: effects of changes in PiO2 and PiCO2.

Periodic breathing of the Biot or cluster type was induced in spontaneously breathing, pentobarbital anesthetized cats by placing bilateral lesions within the pneumotaxic system of the rostral pons. Control lesions positioned outside of the critical nuclei never resulted in Biot breathing. The periodic pattern was characterized by clusters of breaths which were separated by distinct periods of apnea and was clearly not of Cheyne-Stokes quality. Test gas challenges inducing hypoxia and hypercapnia tended to diminish the apneic breatholds, whereas hyperoxia potentiated the periodic breathing by increasing the duration of the non-ventilatory phase. Only hypercapnia significantly altered the tidal volume of Biot breaths by increasing the depth of breathing. No conclusions can be drawn as to whether the Biot pattern arises from an inherent central respiratory controller periodicity, or from oscillations in arterial blood gas tensions and peripheral chemoreceptor (and mechanoreceptor) inputs. It is suggested that the experimental model for Biot breathing may be of unique importance for studying the control of expiratory duration, particularly apnea. Also, it is of interest that similar breathing patterns and gas responses occur in the neonate and adult.

Animals↗

Cat phrenic nucleus architecture as revealed by horseradish peroxidase mapping.

Cat phrenic motoneurons, labeled by intradiaphragmatic injection of horseradish peroxidase, formed a tight cluster in the most ventral portion of the ventral horn in lamina IX of the lower cervical cord. Cell counts were symmetrically distributed for 17 to 21 mm along the longitudinal axis of the cord with a unimodal peak at the junction of segments C5 and C6. The phrenic nucleus was bilaterally organized on either side of the cord with anatomical symmetry and in no case was there evidence for the crossing of phrenic axons in the cord. Assessment of cellular geometry and intercellular relationships demonstrated that phrenic cell diameters approximated a normal distribution with a single peak at 26 mum while longitudinal cell lengths average 76 mum. Cells of different size were mixed randomly at all levels of the nucleus. The minimum distance between cells was about 10 mum and the maximum cell packing density approached 2 cells per 10(6) mum3. The results confirm the location of the cat phrenic nucleus, extend the knowledge of phrenic motoneuronal geometry, and provide an anatomical basis for the understanding of recruitment and synchronization phenomena within the phrenic nucleus.

Animals↗

Pentobarbital-induced apneusis in intact, vagotomized, and pneumotaxic-lesioned cats.

While recording several respiratory parameters, sodium pentobarbital (PB) was infused into the inferior vena cava of spontaneously breathing, PB anesthetized cats. Three cat groups were investigated: intact control (group A); vagotomized (group B); pneumotaxic center-lesioned (group C). With a few exceptions, all cats developed PB-induced inspiratory apneusis. Groups B and C exhibited 10-sec inspiratory hold pattern at significantly lower PB levels than group A cats. All groups developed apnea at different PB levels. Ventilation was consistently depressed, predominantly by breathing frequently attenuation. Tidal volume remained comparable to control, but decreased in vagotomized cats at high PB levels. These results are interpreted to signify that (1) inspiratory inhibitory inputs are more susceptible to depression by PB than inspiratory drive mechanisms; (2) the breathing pattern of apneusis results when summed inspiratory inhibition is reduced below a critical minimum level; (3) vagal and pneumotaxic center inhibitions on inspiration are equally weighted at apneusis, but not at apnea. These results are further discussed in terms of the inspiratory off-switch model. A possible model of Biot respiration is also introduced.

Animals↗

Thoracic dorsal rhizotomy in the anesthetized cat: maintenance of eupnic breathing.

In order to assess the level of participation of thoracic afferents in the determination of the eupnic breathing pattern, thoracic dorsal rhizotomies from T1 through T13 were performed in cats anesthetized with alpha-chloralose or sodium pentobarbital, with or without intact vagi. While recording several respiratory parameters, no consistent changes in the spontaneous breathing pattern could be demonstrated either 10--20 min or 90--100 min following disruption of thoracic afferent input. Thus, respiratory frequency, tidal volume and total ventilation were unaffected by rhizotomy. Inspiratory (TI) and expiratory (TE) durations and TI/TE ratios remained constant. Tracheal air flows during inspiration and expiration and intrapleural pressure were not altered. Finally, end-expiratory %CO2 and %O2 did not change after section of the thoracic dorsal roots. Only arterial blood pressure was found to fall as a function of time into the experiment. Since the results were identical in vagotomized and in vagi intact preparations, thoracic reflexes were not being masked by vagal dominance in eupnea. Rather, thoracic afferents, including intercostal muscle spindle afferents, appear to be ineffective in shaping the pattern of quiet breathing in anesthetized cats. This is unlike situations of loaded or stressed breathing where these afferents assume a more active role in the modulation of rate and depth mechanisms.

Afferent Pathways↗

Ascending spinal pathways for the somatosympathetic A and C reflexes.

Sympathetic unit nerve activity was recorded from the cervical sympathetic trunk of anesthetized, vagotomized, and carotid sinus-denervated cats. Single pulses or short trains of pulses with suprathreshold intensity for afferent C fibers were applied to the common peroneal nerve to elicit somatosympathetic A or simultaneous A and C reflexes, respectively. Bilateral lesions of an ascending spinal pathway in the dorsolateral sulcus area (DLS) of the T12 spinal cord eliminated the sympathetic C reflex. The remaining somatosympathetic A reflex was abolished by the subsequent lesion of an ascending spinal pathway in the dorsolateral funiculus (DLF) bilaterally. The duration of the silent period was found to be mainly influenced by an ascending spinal pathway in the DLF. It was concluded that excitation of afferent A fibers activates ascending pathways mainly in the DLF and a smaller contribution in the DLS of the spinal cord. This produces a small reflex excitation (A reflex) followed by a long silent period in the sympathetic nerves resulting in a net decrease of total sympathetic nerve activity. On the other hand, excitation of afferent C fibers activates the ascending spinal pathway in the DLS. This produces a reflex excitation (C reflex) which exceeds the decreased activity due to the silent period resulting in a net increase of total sympathetic nerve activity.

Action Potentials↗

Structural and functional characteristics of individual phrenic motoneurons.

Intracellular recording and staining techniques were applied to the study of cat phrenic motoneurons. Spontaneously driven phrenic cells possessed individualistic depolarization and spiking patterns that were a function of the conduction velocity in the different motor axons. Staining of phrenic motoneurons with Procion yellow indicated that fast conducting cells with small slow-wave depolarizations were large in size while slow conducting cells with large depolarizations were small in size. This implicated differences in membrane input resistance between large and small cells, although an unequal distribution of inputs to the individual components could not be discounted. On the average, phrenic motoneurons had a smaller dendritic surface area and smaller dendritic dominance than lumbosacral motoneurons. These factors help to explain the higher membrane resistances and longer time constants of phrenic cells. Phrenic dendrites were found to project in all directions away from the cell body and form ellipsoidal receptive fields that overlapped with other phrenic fields. It is speculated that the close approximation of phrenic dendrites with one another could, in part, be responsible for the high degree of synchronization among the different phrenic units.

Animals↗

Interaction of respiratory cell discharge patterns and spontaneous resporatory rate.

Potentials from single respiratory cells in the inspiratory and expiratory populations of the medulla were recorded by extracellular microelectrodes in spontaneously breathing cats anesthetized with pentobarbital. Experiments were designed to follow alterations in single-cell discharge patterns after modification of the respiratory rate by either barbiturate depression or doxapram activation. Unit activity was quantitated by a computerized mathematical technique based on the sequential arrangement of interspike intervls. From this analysis several discharge parameters were derived which successfully quantitated initial (frequency increase), middle (frequency plateau), and terminal (frequency decrease) phases of spike activity. Discharge parameters were correlated with respiratory rate by the use of linear and curvilinear regression analyses. Theoretical discharge patterns for both inspiratory and expiratory populations were reconstructed at selected respiratory rates by interpolation from regression equations. These data, demonstrating average quantitative shifts in cell activation and deactivation phases as a function of respiratory rate, suggested several possibilities for the modulation of the respiratory frequency.

Action Potentials↗