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Biomedical subjects

D Bartlett

Publications and source records attributed to D Bartlett.

At least 73 records · Page 4Linked to original sources

A decrease in nasal CO2 stimulates breathing in the tegu lizard.

Tegu lizards decrease ventilatory frequency (f) when constant CO2, as low as 0.4%, is delivered to the nasal cavities. In contrast, CO2, as high as 6%, pulsed into the nasal cavities during the expiratory phase of the breathing cycle does not alter f. The purpose of the present study was to investigate further the effect of nasal CO2 pattern on f in tegu lizards. Specifically, we tested: (1) whether f was affected by CO2 delivered to the nasal cavities during the inspiratory phase of the breathing cycle, and (2) whether pulsed decreases in nasal CO2 from 4% to 2% and from 4% to 0% would remove the f inhibition caused by constant nasal CO2. Ventilation was measured using a pneumotachograph and pressure transducer in-line with an endotracheal T-tube inserted through the glottis. CO2 was delivered to the nasal cavities through small tubes inserted into the external nares. Ventilatory frequency was not significantly altered when 4% CO2 was pulsed into the nasal cavities during inspiration. Dropping the CO2 in the nasal cavities from 4% to 0% at either 15 cycles/min (0.25 Hz) or for one cycle stimulated breathing. There was no significant difference between the f response to a drop in CO2 from 4% to 0% and that to a drop in CO2 from 4% to 2%. The failure to link the phasic CO2 ventilatory response to a phase in the respiratory cycle indicates that the nasal CO2 receptors do not participate in the breath-by-breath regulation of breathing in these lizards. The observation that small decreases in nasal CO2 abolished the f inhibition caused by constant nasal CO2 provides further evidence for the ability of the nasal CO2 receptors to distinguish between pulsed and constant CO2.

Animals↗

The influence of venous CO2 on ventilation in garter snakes.

Garter snakes were used to study the effects of venous CO2 loading using the skin as an exchanger. The gaseous environment surrounding the snake's body was isolated by placing the body in a plethysmograph with the head out. While the animal breathed room air, the carbon dioxide concentration within the plethysmograph was varied between 0 and 80%. Room air was drawn through a funnel placed over the snake's head, thus collecting the exhaled gases, and this gas was analyzed by O2 and CO2 analyzers. The descending aorta was cannulated to measure blood gases. Expired CO2 flow rose linearly with increasing cutaneous CO2. Ventilation increased 3.5-fold at 80% cutaneous CO2 compared with no cutaneous CO2 load. Neither the mean CO2 concentration in exhaled air nor arterial PCO2 changed when the snake was exposed to high levels of CO2 at the skin. Thus ventilation increased in proportion to the CO2 load, and was not driven by arterial hypercapnia. Bilateral vagotomy eliminated arterial CO2 homeostasis during cutaneous CO2 loading, and ventilation increased with increasing arterial PCO2. Therefore, these snakes respond to extra-arterial elevations in CO2 or to a changing CO2 signal. Furthermore, receptors responsible for the increase in ventilation when venous CO2 is elevated have neurons in the vagus nerves.

Animals↗

Nasal and pharyngeal resistance after topical mucosal vasoconstriction in normal humans.

Phenylephrine, an alpha-adrenergic agonist, increases pharyngeal cross-sectional area when applied topically to the nasal and pharyngeal mucosa, as determined by magnetic resonance imaging. In this study, we examined the possibility that the increase in area results from either a decrease in transmural collapsing pressure, as a result of a decrease in upstream (nasal) resistance, or an increase in upper airway muscle activity. In eight normal, awake men we measured inspiratory pharyngeal and nasal resistance and the electrical activity of the genioglossus (EMGGG) and alae nasi (EMG(AN) before and after pharyngeal and nasal + pharyngeal instillation of 1 ml of either 0.25% phenylephrine or normal saline; phenylephrine and saline were tested on separate days. Under control eucapnic conditions, pharyngeal resistance was 0.43 +/- 0.03 cm H2O/L/s, and nasal resistance was 2.43 +/- 0.14 cm H2O/L/s. Pharyngeal resistance was 0.29 +/- 0.03 cm H2O/L/s after nasal + pharyngeal instillation of phenylephrine and 0.98 +/- 0.13 cm H2O/L/s after saline; nasal resistance was 2.18 +/- 0.13 cm H2O/L/s after nasal + pharyngeal instillation of phenylephrine and 3.15 +/- 0.21 cm H2O/L/s after saline. Thus, phenylephrine decreased both nasal and pharyngeal inspiratory resistance. The change in pharyngeal resistance was not dependent on the change in nasal resistance. Eucapnic EMGGG and EMGAN activities did not change after phenylephrine or saline. We conclude that phenylephrine decreased pharyngeal resistance independent of a change in nasal resistance of upper airway muscle activity, and we believe that the changes in resistance we observed reflect a direct effect of phenylephrine on the pharyngeal mucosa and a consequent enlargement of pharyngeal size.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Influence of phasic volume feedback on abdominal expiratory nerve activity.

Our purpose was to examine the influence of phasic lung volume feedback on the activities of motor nerves innervating the diaphragm and transversus abdominis muscles during hypercapnia and hypoxia. We studied seventeen decerebrate cats that were paralyzed and ventilated with a servo-respirator controlled by the integrated phrenic neurogram. The effects of phasic lung volume feedback were assessed by withholding pulmonary inflation during the central inspiratory period. Withholding lung inflation for a single respiratory cycle under hyperoxic, normocapnic conditions consistently prolonged the durations of the inspiratory and expiratory periods, and caused marked increases in the peak electrical activities of both phrenic and abdominal nerves. Hyperoxic hypercapnia (PaCO2 50-80 mmHg) and isocapnic hypoxia (PaO2 60-35 mmHg) increased peak phrenic and abdominal neural activities, and withholding pulmonary inflation under these conditions caused even greater augmentations of inspiratory and expiratory motor output. The augmentation of expiratory activity by withholding lung inflation was proportionately greater than the concomitant prolongation of the central expiratory period. All responses to non-inflation maneuvers were abolished following bilateral cervical vagotomy. The results indicate that vagally mediated volume feedback during inspiration can attenuate the output of abdominal motoneurons in the subsequent expiratory period. Moreover, hypoxia, which attenuates abdominal motor activity in vagotomized animals, enhances this activity when the vagi are intact.

Animals↗

Isolation of a gene regulated by hydrostatic pressure in a deep-sea bacterium.

Barophilic bacteria inhabit the deep oceans, and the specific functional modifications and regulatory mechanisms which govern adaptation to hydrostatic pressure are beginning to be understood. For example, the rate of production of several proteins by some hydrothermal vent archaebacteria and the degree of saturation of membrane lipids in other deep-sea bacteria have been found to change as a result of cultivation at high pressure. We report here the cloning of gene, ompH, which encodes a major pressure-inducible protein of strain SS9, a gram-negative eubacterium isolated from a depth of 2.5 kilometres in the Sulu Sea. Messenger RNA encoded by ompH is expressed when cells are grown at 280 atm but not at 1 atm, indicating that transcription of the ompH gene is controlled by hydrostatic pressure. The function of the OmpH protein in adaptation to high pressure and the use of the ompH gene in studying how bacteria sense and respond to pressure is discussed.

Amino Acid Sequence↗

Activities of pulmonary stretch receptors during ventilatory cycles without lung inflation.

When lung inflation is temporarily withheld in paralyzed, ventilated cats with intact vagi, the activities of inspiratory motor nerves are greater during the second cycle without inflation than during the first. This response is not easily attributable to increasing drive from chemoreceptors as it is abolished by vagotomy. We examined the hypothesis that the increasing inspiratory activity is the result of decreasing inhibitory feedback from pulmonary stretch receptors (PSRs). Decerebrate, paralyzed cats were ventilated by a servo-respirator in accordance with their own phrenic nerve activity. Afferent activities from individual PSRs were recorded from a few cut fibers of one vagus nerve; the vagi were otherwise intact. When lung inflation was withheld, phrenic and hypoglossal nerve activities and the durations of inspiration and expiration all increased and were significantly greater during the second cycle without inflation than during the first. The frequency of PSR discharge was also greater during the second cycle and thus did not account for the responses recorded from the motor nerves. We conclude that the latter responses probably reflect neural processes within the brain stem, involving a persistent inhibitory influence from lung inflation, which outlasts the inflation itself.

Animals↗

Reflex inhibition of crural diaphragmatic activity by esophageal distention in cats.

Distention of the esophagus has been shown to result in selective inhibition of phasic inspiratory activity in the crural portion of the diaphragm, with no effect on costal diaphragmatic activity. The purpose of this study was to determine rigourously the afferent pathways that mediate this response. Bipolar EMG electrodes were placed in the costal and crural portions of the diaphragm in decerebrate, spontaneously breathing cats. Distention of the esophagus by inflation of a Foley catheter balloon with 20 ml of air resulted in a selective inhibition of crural hiatal EMG activity, while costal EMG activity was maintained at predistention levels. The distention was accompanied by a reduction in respiratory frequency. Transection of the spinal cord at the C8-T1 level did not obliterate the crural inhibition produced by inflation. Section of the C4-C8 dorsal roots also failed to abolish the response. However, after bilateral cervical vagotomy, esophageal distention no longer influenced diaphragmatic EMG activity. These results indicate that the crural inhibition observed with esophageal distention is vagally mediated and is not influenced importantly by intercostal or phrenic afferents. Records of activity of the phrenic nerve branch innervating the crural portion of the diaphragm showed a similar response pattern, confirming that the inhibition is central in origin and that the crural fibers inhibited by distention are only a fraction of the total population of crural phrenic motoneurons.

Animals↗

Intrapulmonary CO2 inhibits inspiration in garter snakes.

This study was undertaken to assess the role of intrapulmonary chemoreceptors in the control of breathing in reptiles. Garter snakes were tracheostomized to remove the influence of upper airway receptors. After recovery from anesthesia, the animals were unidirectionally ventilated or allowed to ventilate normally, but without glottal control of the breath-hold. Breathing movements were recorded by means of a pneumotachograph. When a bidirectionally breathing snake was presented with CO2 at the tracheal tube, inspiratory duration and volume decreased. When CO2 was removed from the inspired air between breaths, inspiratory duration and volume increased. Removing CO2 from the airstream of a unidirectionally ventilated snake during a breath-hold produced apnea, but removing CO2 at the beginning of inspiration caused the duration and volume of the inspiration to increase. This reflex appears to represent a positive feedback mechanism for enhancing inspiration once a breath has been initiated.

Animals↗

Internal intercostal nerve discharges in the cat: influence of chemical stimuli.

We studied the influence of central and peripheral chemoreceptor stimulation on the activities of the phrenic and internal intercostal (iic) nerves in decerebrate, vagotomized, and paralyzed cats with bilateral pneumothoraces. Whole iic nerves of the rostral thorax (T2-T5) usually discharged during neural inspiration, whereas those of the caudal thorax (T7-T11) were primarily active during neural expiration. Filaments of rostral iic nerves that terminated in iic muscles generally discharged during expiration, suggesting that inspiratory activity recorded in whole iic nerves may have innervated other structures, possibly parasternal muscles. All nerves were phasically active at hyperoxic normocapnia and increased their activities systematically with hypercapnia. Isocapnic hypoxia or intra-arterial NaCN injection consistently increased phrenic and inspiratory iic nerve activities. In contrast, expiratory iic nerve discharges were either decreased (10 cats) or increased (7 cats) by hypoxia. Furthermore, expiratory responses to NaCN were highly variable and could not be predicted from the corresponding response to hypoxia. The results show that central and peripheral chemoreceptor stimulation can affect inspiratory and expiratory motoneuron activities differentially. The variable effects of hypoxia on expiratory iic nerve activity may reflect a relatively weak influence of carotid body afferents on expiratory bulbospinal neurons. However, the possibility that the magnitude of expiratory motoneuron activity is influenced by the intensity of the preceding centrally generated inspiratory discharge is also discussed.

Action Potentials↗

Patterns of neural and muscular electrical activity in costal and crural portions of the diaphragm.

To determine whether the central respiratory drives to costal and crural portions of the diaphragm differ from each other in response to chemical and mechanical feedbacks, activities of costal and crural branches of the phrenic nerve were recorded in decerebrate paralyzed cats, studied either with vagi intact and servo-ventilated in accordance with their phrenic nerve activity or vagotomized and ventilated conventionally. Costal and crural electromyograms (EMGs) were recorded in decerebrate spontaneously breathing cats. Hypercapnia and hypoxia resulted in significant increases in peak integrated costal, crural, and whole phrenic nerve activities when the vagi were either intact or cut. However, there were no consistent differences between costal and crural neural responses. Left crural EMG activity was increased significantly more than left costal EMG activity in response to hypercapnia and hypoxia. These results indicate that the central neural inputs to costal and crural portions of the diaphragm are similar in eupnea and in response to chemical and mechanical feedback in decerebrate paralyzed cats. The observed differences in EMG activities in spontaneously breathing animals must arise from modulation of central respiratory activity by mechanoreceptor feedback from respiratory muscles, likely the diaphragm itself.

Animals↗

Respiratory activities of intralaryngeal branches of the recurrent laryngeal nerve.

To distinguish experimentally between motor nerve activity destined for vocal cord abductor muscles and that bound for muscles that adduct the cords, we recorded efferent activities of intralaryngeal branches of the recurrent laryngeal nerve (RLN) in decerebrate, vagotomized, paralyzed, ventilated cats. Activities of the whole RLN and phrenic nerve were also recorded. Nerve activities were assessed at several steady-state end-tidal O2 and CO2 concentrations. The nerve to the thyroarytenoid (TA) muscle, a vocal cord adductor, was only slightly active under base-line (normocapnic, hyperoxic) conditions but in most cats developed strong activity during expiration in hypocapnia or hypoxia. In severe hypocapnia, phasic expiratory TA activity persisted even during phrenic apnea, indicating continuing activity of the respiratory rhythm generator. The nerve to the posterior cricoarytenoid (PCA) muscle, the vocal cord abductor, was always active in inspiration but often showed expiratory activity as well. This expiratory activity was usually enhanced by hypercapnia and often inhibited by hypoxia. The results are consistent with previous electromyographic findings and emphasize the importance of distinguishing abductor from adductor activity in studies of laryngeal control.

Animals↗

Influence of lung volume on activities of branches of the recurrent laryngeal nerve.

To investigate the influence of inspiratory lung inflation on the respiratory activities of laryngeal motor nerves, vagally intact decerebrate paralyzed cats were ventilated by a servorespirator in accordance with their own phrenic nerve activity. Records were made of the activities of the phrenic nerve, the superior laryngeal nerve (SLN), the recurrent laryngeal nerve (RLN), and the intralaryngeal branches of the RLN serving the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles. Neural activities were assessed in the steady state at different end-tidal O2 and CO2 concentrations. Transient responses to withholding inspiratory lung inflation and to preventing expiratory lung emptying were also studied. Hypercapnia and hypoxia increased the inspiratory activities of the phrenic nerve, SLN, RLN, and its PCA branch. TA inspiratory activity was not changed. Expiratory activities of RLN, PCA, and TA were all increased in hypoxia. When lung inflation was withheld, neural inspiratory duration and the inspiratory activities of all nerves increased. The subsequent period of neural expiration was marked by an exaggerated burst of activity by the TA branch of the RLN. TA expiratory activity was also sharply increased after inspiratory efforts that were reflexly delayed by the prevention of lung emptying. TA activity in expiration was enhanced after vagotomy and was usually more prominent than when lung inflation was withheld before vagal section. The results demonstrate the importance and complexity of the influence of vagal afferents on laryngeal motor activity.

Afferent Pathways↗

An inexpensive servo-respirator based upon regulation of a shunt resistance.

We have designed and built an inexpensive servo-respirator for use in investigations of respiratory control in small animals. The device uses a butterfly valve to alter the resistance of an outflow shunt from a manifold that connects the animal's tracheal cannula to a pressure source. Tracheal pressure is regulated in response to a command provided by a suitably processed neural signal, often the integrated phrenic neurogram. As the valve opens, tracheal pressure approaches atmospheric; as it closes, tracheal pressure approaches the source pressure. An electronic controller circuit was developed to permit experimental procedures that include withholding volume delivery while maintaining a desired level of positive end-expiratory pressure. The device is able to track the neural command signal satisfactorily, and its performance appears to be limited primarily by the constraints applied by the respiratory system mechanics.

Airway Resistance↗

Influence of lung volume on phrenic, hypoglossal and mylohyoid nerve activities.

In decerebrate, paralyzed cats, ventilated by a servo-respirator in accordance with phrenic nerve activity, we examined the influence of lung volume on the activities of the phrenic, hypoglossal and mylohyoid nerves. When lung inflation was briefly withheld, the durations of inspiration (TI) and expiration (TE) and the activities of all three nerves increased. The relative increase in hypoglossal activity greatly exceeded that of phrenic activity and was apparent earlier in the course of inspiration. This hypoglossal response was enhanced by hypercapnia and isocapnic hypoxia. The responses of mylohyoid activity were quite variable: withholding lung inflation augmented inspiratory activity in some cats, but expiratory discharge in others. Sustained increases in end-expiratory lung volume were induced by application of 3-4 cm H2O of positive end-expiratory pressure (PEEP). Steady-state PEEP did not influence nerve activities or the breathing pattern. Bilateral vagotomy increased TI, TE, and the activities of all three nerves. No response to withoholding lung inflation could be discerned after vagal section. The results provide further definition of the influence of vagally mediated, lung volume dependent reflexes on the control of upper airway muscles. These reflexes are well suited to relieve or prevent upper airway obstruction.

Animals↗

Central inspiratory influence on abdominal expiratory nerve activity.

Our purpose was to determine whether the intensity of abdominal expiratory nerve discharge is conditioned by the intensity of the preceding inspiratory phrenic discharge, independent of mechanical and chemical afferent influences. In decerebrate, paralyzed, vagotomized cats with bilateral pneumothoraxes, we recorded phrenic and abdominal (cranial iliohypogastric nerve, L1) nerve activities at hyperoxic normocapnia. We reduced the duration and intensity (i.e., integrated peak height) of phrenic nerve discharge for single cycles by stimulating the cut central end of the superior laryngeal nerve (SLN) during the central inspiratory phase (75 microA, 20-50 Hz, 0.2-ms pulse). Premature termination of inspiration consistently reduced expiratory duration (TE) and abdominal expiratory nerve activity (area of integrated neurogram), but the average reduction in TE was much less than the reduction in abdominal nerve activity (14 vs. 51%). Stimulation of the cut central end of the vagus nerve yielded similar results, as did spontaneous premature terminations of inspiration, which we observed in one cat. SLN stimulation during hyperoxic hypercapnia resulted in more variable responses, and higher stimulation frequencies were usually required to abort inspiration. SLN (or vagal) stimulation during expiration consistently increased abdominal expiratory nerve activity. We speculate that this facilitatory response is gated during inspiration, thereby allowing the inspiratory conditioning effect on the subsequent expiration to be expressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗

Changes in phrenic, mylohyoid, and hypoglossal nerve activities that follow intravenous infusions of aminophylline.

We determined whether or not administrations of aminophylline would produce differential changes in activities of the hypoglossal nerve and the mylohyoid branch of the trigeminal nerve, compared with phrenic nerve activity. The former two nerves innervate muscles influencing the upper airway, whereas the phrenic nerve innervates the diaphragm, a major muscle of the ventilatory pump. Neural activities were recorded in decerebrate, vagotomized, paralyzed, and ventilated cats. Peak integrated phrenic activity generally increased with intravenous infusions of cumulative doses of aminophylline ranging from 1.0 to 64 mg/kg. The concomitant changes in trigeminal and hypoglossal activities were extremely variable. In some animals, peak integrated trigeminal and/or hypoglossal activities rose progressively with increasing doses of aminophylline. For other animals, maximum levels of neural activities were attained at intermediate doses and declined at higher dose levels. Results were similar in animals having bilateral sections of the carotid sinus nerves. The variable changes in neural activities may reflect the multiple sites of action of aminophylline in the brain stem.

Action Potentials↗