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Biomedical subjects

J E Remmers

Publications and source records attributed to J E Remmers.

At least 37 records · Page 2Linked to original sources
PubMed2000

Significance of vagal innervation in perinatal breathing and gas exchange.

The mechanisms responsible for the establishment of continuous breathing at birth remain unknown. Several studies have shown that postnatal vagal denervation produces deleterious effects on ventilation as well as breathing patterns during the newborn period. However, the validity of these studies was compromised by anesthesia, tracheostomy or possible secondary laryngeal obstruction. We have recently developed an unanesthetized lamb model in which vagal denervation was performed antenatally and below the recurrent laryngeal nerves thereby avoiding anesthesia, tracheostomy and laryngeal paralysis. The denervated animals developed life-threatening respiratory failure shortly after birth, implying that vagal innervation of the lungs plays an essential role in establishing adequate gas exchange in the first hours after birth. We have subsequently investigated various mechanisms of respiratory failure in denervated animals. Our results show that the surfactant system dysfunction and loss of vagally mediated volume feedback likely contributed to the respiratory failure observed in the intrathoracically denervated animal model.

Animals↗
PubMed2000

Automated analysis of digital oximetry in the diagnosis of obstructive sleep apnoea.

BACKGROUND: The gold standard diagnostic test for obstructive sleep apnoea (OSA) is overnight polysomnography (PSG) which is costly in terms of time and money. Consequently, a number of alternatives to PSG have been proposed. Oximetry is appealing because of its widespread availability and ease of application. The diagnostic performance of an automated analysis algorithm based on falls and recovery of digitally recorded oxygen saturation was compared with PSG. METHODS: Two hundred and forty six patients with suspected OSA were randomly selected for PSG and automated off line analysis of the digitally recorded oximeter signal. RESULTS: The PSG derived apnoea hypopnea index (AHI) and oximeter derived respiratory disturbance index (RDI) were highly correlated (R = 0.97). The mean (2SD) of the differences between AHI and RDI was 2.18 (12.34)/h. The sensitivity and specificity of the algorithm depended on the AHI and RDI criteria selected for OSA case designation. Using case designation criteria of 15/h for AHI and RDI, the sensitivity and specificity were 98% and 88%, respectively. If the PSG derived AHI included EEG based arousals as part of the hypopnea definition, the mean (2SD) of the differences between RDI and AHI was -0.12 (15. 62)/h and the sensitivity and specificity profile did not change significantly. CONCLUSIONS: In a population of patients suspected of having OSA, off line automated analysis of the oximetry signal provides a close estimate of AHI as well as excellent diagnostic sensitivity and specificity for OSA.

Adult↗
PubMed2000

Evolution of air-breathing and central CO(2)/H(+) respiratory chemosensitivity: new insights from an old fish?

While little is known of the origin of air-breathing in vertebrates, primitive air breathers can be found among extant lobe-finned (Sarcopterygii) and ray-finned (Actinopterygii) fish. The descendents of Sarcopterygii, the tetrapods, generate lung ventilation using a central pattern generator, the activity of which is modulated by central and peripheral CO(2)/H(+) chemoreception. Air-breathing in Actinopterygii, in contrast, has been considered a 'reflexive' behaviour with little evidence for central CO(2)/H(+) respiratory chemoreceptors. Here, we describe experiments using an in vitro brainstem preparation of a primitive air-breathing actinopterygian, the longnose gar Lepisosteus osseus. Our data suggest (i) that gill and air-breathing motor patterns can be produced autonomously by the isolated brainstem, and (ii) that the frequency of the air-breathing motor pattern is increased by hypercarbia. These results are the first evidence consistent with the presence of an air-breathing central pattern generator with central CO(2)/H(+) respiratory chemosensitivity in any primitive actinopterygian fish. We speculate that the origin of the central neuronal controller for air-breathing preceded the divergence of the sarcopterygian and actinopterygian lineages and dates back to a common air-breathing ancestor.

Animals↗
PubMed1999

Premotor input to hypoglossal motoneurons from Kölliker-Fuse neurons in decerebrate cats.

Experiments were performed in 18 paralysed, ventilated, decerebrate adult cats to characterise projections from the Kölliker-Fuse nucleus(KFN) to hypoglossal(HG) motoneurons. Efferent neural activity was recorded from the medial branch of both HG nerves, right recurrent laryngeal(RL) nerve, and C3 branch of the left phrenic nerve. Electrical stimulation(1 Hz, 1 msec pulse duration) of discrete areas within the KFN coordinates elicited a preferential, predominantly ipsilateral burst of HG action potentials with an average stimulus-response latency of 8 msec. Tonic stimulation(5-20 Hz) frequently produced considerable HG temporal summation and the appearance of phasic inspiratory HG activity. Injection of 40-100 nl kainic acid(6.37 mM) into the rostral pontine site with the lowest electrical threshold for HG activation elicited a prolonged tonic HG activation. Following kainate injection, the electrical stimulation threshold for HG excitation increased. Pressure injections of 5-100 nl of 2 mM N-methyl-D-aspartic acid (NMDA)and 2 mM(+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide(AMPA) into the KFN were associated with activation and/or suppression of HG motor output. The results indicate that HG motoneurons innervating protrusor tongue muscles receive a selective projection from the KFN that can be activated by glutamate receptors on KF neurons.

Action Potentials↗
PubMed1999

Efficacy of a low volume recirculating superfusion chamber for long term administration of expensive drugs and dyes.

We have characterized the efficacy of a low volume (2 ml) two-compartment experimental chamber in which a gas inflow equilibrates and recirculates the bathing fluid. This type of chamber is suitable for experiments employing en bloc preparations that require the administration of expensive molecular probes. The fluid in the chamber is pumped from a compartment holding the preparation to an elevated reservoir compartment using gas bubbles. The fluid returns via gravity along a different path. The flow rate of superfusate in the chamber was 30 ml min(-1). To determine the effectiveness of the chamber in dissolving gas, we filled the chamber with bicarbonate-buffered physiological saline and measured pH and P(O(2)) with ion-selective and Clark-style microelectrodes. Steady state values of pH and P(O(2)) in the chamber were almost identical to those in an external tonometer bubbled vigorously with the same gas mixture. When CO(2) was increased from 2 to 4.4%, the chamber pH fell with a time constant of 56 s (about twice that of the tonometer). To determine the effectiveness of gas exchange between a brain preparation and the fluid in the chamber we measured pH and P(O(2)) depth profiles of the in vitro tadpole brainstem. We found virtually no unstirred layer owing to excellent mixing and the high flow created by the recirculating mechanism. We demonstrate that despite the high flow rates, preparations are mechanically stable allowing intracellular electrophysiological recordings.

Animals↗
PubMed1999

The fictively breathing tadpole brainstem preparation as a model for the development of respiratory pattern generation and central chemoreception.

Spontaneous high-frequency, low-amplitude and low-frequency, high-amplitude efferent bursting patterns of cranial and spinal motor nerve activity in the in vitro brainstem preparation of the bullfrog tadpole Rana catesbeiana have been characterized as fictive gill and lung ventilation, respectively (Gdovin MJ, Torgerson CS, Remmers JE). Characterization of gill and lung ventilatory activity in cranial nerves in the spontaneously breathing tadpole Rana catesbeiana, FASEB J 1996;10(3):A642; Gdovin MJ, Torgerson CS, Remmers JE. Neurorespiratory pattern of gill and lung ventilation in the decerebrate spontaneously breathing tadpole, Respir Physiol 1998;113:135 146; Pack AI, Galante RJ, Walker RE, Kubin LK, Fishman AP. Comparative approach to neural control of respiration, In: Speck DF, Dekin MS, Revelette WR, Frazier DT, editors. Respiratory Control Central and Peripheral Mechanisms. Lexington: University of Kentucky Press, 1993:52-57). In addition, the ontogenetic dependence of central respiratory chemoreceptor stimulation on fictive gill and lung ventilation has been previously described (Torgerson CS, Gdovin MJ, Remmers JE. Fictive gill and lung ventilation in the pre- and post-metamorphic tadpole brainstem, J Neurophysiol 1998, in press). To investigate the neural substrates responsible for central respiratory rhythm generation of gill and lung ventilation in the developing tadpole, we recorded efferent activities of cranial nerve (CN) V, VII, and X and spinal nerve (SN) II during changes in superfusate PCO2 before and after multiple transection of the in vitro brainstem. The brainstem was transected between CN VIII and IX and the response to changes in PCO2 was recorded. A second transection was then made between the caudal margin of CN X and rostral to SN II. Preliminary data reveal that robust gill ventilation was recorded consistently only if the segment of brainstem included CN X, whereas the loci capable of eliciting fictive lung bursting patterns appeared to differ depending on developmental stage. These data demonstrate that the neural substrate required for fictive gill and lung ventilation exists in anatomically separate regions such that the gill central pattern generator (CPG) is located in the caudal medulla at the level of CN X throughout development, whereas the location of the lung CPG is located more rostrally at the level of CN VII in the post-metamorphic larva. Both in vivo and in vitro studies revealed two distinct neural bursting patterns associated with gill and lung ventilation. Sequential activation of CN V, VII, X were observed during gill ventilation of in vivo and fictive gill ventilation in vitro, whereas these nerve activities, along with SN II displayed more synchronous bursting patterns of activation during lung ventilation and fictive lung breaths.

Animals↗
PubMed1999

Estimating respiratory mechanics in the presence of flow limitation.

Dynamic collapse of the pulmonary airways, leading to flow limitation, is a significant event in a number of respiratory pathologies, including obstructive sleep apnea syndrome and chronic obstructive pulmonary disease. Quantitative evaluation of the mechanical status of the respiratory system in these conditions provides useful insights into airway caliber and tissue stiffness, which are hallmarks of such abnormalities. However, assessing respiratory mechanics in the presence of flow limitation is problematic because the single-compartment linear model on which most assessment methods are based is not valid over the entire breath. Indeed, even deciding which parts of a breath are flow limited from measurement of mouth flow and pleural pressure often proves to be difficult. In this study, we investigated the use of two approaches to assessing the overall mechanical properties of the respiratory system in the presence of inspiratory flow limitation. The first method is an adaptation of the classic Mead-Whittenberger method, and the second method is based on information-weighted histograms obtained from recursively estimated signals of respiratory resistance and elastance. We tested the methods on data simulated by using a computer model of the respiratory system and on data collected from obese sleeping pigs. We found that the information-weighted histograms provided the more robust overall estimates of respiratory mechanics.

Air Pressure↗
PubMed1999

Monitoring respiratory function and sleep in the obese Vietnamese pot-bellied pig.

Development of drug treatments for obstructive sleep-disordered breathing has been impeded by the lack of animal models. The obese pig may be a suitable animal model, as it has been reported to experience sleep-disordered breathing resembling human obstructive sleep apnea. The purpose of this paper is to describe in detail techniques for chronic instrumentation of the obese Vietnamese pot-bellied pig and to study respiratory function during sleep. Under general anesthesia, four obese pigs were instrumented for long-term recording of intrapleural and tracheal pressures, genioglossal EMG, and bioelectric signals related to sleep. A custom-fitted face mask was used to record respiratory variables including airflow, snoring, and expired CO(2). Most chronic instrumentation provided robust signals for up to 6 wk after installation. All pigs displayed sleep-disordered breathing characterized by increased resistance to airflow, snoring, inspiratory flow limitation, and possible sleep disruption. Apneas and hypopneas were not a feature of breathing during sleep in these animals. Nonetheless, this animal preparation may be useful for exploring possible drug treatments for obstructive sleep-disordered breathing.

Animals↗
PubMed1999

A comparison of apnea-hypopnea indices derived from different definitions of hypopnea.

We examined the effects of arousal- and desaturation-based scoring criteria on the apnea-hypopnea index (AHI) and on the measured prevalence of obstructive sleep apnea (OSA). Ninety-four randomly selected patients underwent overnight polysomnography. Studies were scored according to three different criteria for hypopnea, as defined by a >= 10 s discernible reduction in thoracoabdominal movement associated with: (1) >= 4% decrease in oxygen saturation (SaO2) (Type A); (2) either a >= 4% decrease in SaO2 or an arousal (Type B); or (3) electroencephalographically based arousal alone (Type C). Excellent correlation existed between AHI-A, AHI-B, and the oxygen desaturation index (ODI) (r > 0.98). AHI-A and AHI-B differed by only 2.04 +/- 1.72/h (2 SD). AHI-A and AHI-B differed from the ODI by 1.04 +/- 4.07/h and 3.07 +/- 4.30/h, respectively. Despite these small differences, use of the Type B rather than Type A definition resulted in an extra case of OSA being diagnosed for every 14 to 31 patients tested, depending on the definition of OSA (AHI: >= 5, 10, 15, or 20/h). The addition of arousal-based scoring criteria for hypopnea causes only small changes in the AHI, but if OSA is defined solely by an AHI value, the measured prevalence of OSA will increase.

Adult↗
PubMed1998

Neurorespiratory pattern of gill and lung ventilation in the decerebrate spontaneously breathing tadpole.

A decerebrate, spontaneously breathing tadpole preparation (Taylor-Kollros stages 16-19) was used to test the general hypothesis that the efferent bursting activities of cranial nerves (CN) V, VII and spinal nerve (SN) II are respiratory in nature, and, in particular, to identify separate and specific neural correlates of gill and lung ventilation. Oropharyngeal pressure (POP), intrapulmonary pressure (PIP), electromyogram (EMG) of the buccal levator muscle (interhyoideus), and efferent neural activities of CN V, CN VII and SN II were recorded while the animal was exposed to hyperoxia (100% inspired O2), normoxia (21% inspired O2), and hypoxia (10, 5 and 0% inspired O2). Gill ventilation, indicated by fluctuations in POP at constant PIP, was characterized by high-frequency, low-amplitude bursts of action potentials in CN V and VII and interhyoideus EMG without phasic activity in SN II. Lung breaths, indicated by oscillations in POP and PIP were characterized by large bursts in EMG, CN V and VII together with a large burst in SN II. The amplitude of the moving average of nerve activities associated with lung ventilation was significantly larger than those associated with gill ventilation. During gill ventilation, the burst in CN V led that in CN VII, and both preceded the rise in POP. By contrast, a more synchronous neural burst onset pattern was observed during lung ventilation. The results document the neural, muscular, and mechanical characteristics of gill and lung ventilation in the tadpole, and establish bursting activity in SN II as a specific marker for lung ventilation in the metamorphic tadpole.

Action Potentials↗
PubMed1998

Pulmonary vagal innervation is required to establish adequate alveolar ventilation in the newborn lamb.

To investigate the effects of bilateral intrathoracic vagotomy on the establishment of continuous breathing and effective gas exchange at birth, we studied 8 chronically instrumented, unanesthetized, sham-operated and 14 vagotomized newborn lambs after a spontaneous, unassisted vaginal delivery. Fetal lambs were instrumented in utero to record sleep states, diaphragmatic electromyogram, blood pressure, arterial pH, and blood-gas tensions. Six of eight sham-operated lambs established effective gas exchange within 10 min of birth, whereas 12 of 14 vagotomized animals developed respiratory acidosis and hypoxemia (P = 0.008). Breathing frequency in vagotomized newborns was significantly lower during the entire postnatal period compared with sham-operated newborns. Vagotomized subjects also remained hypothermic during the entire postnatal period (P < 0.05). Bronchoalveolar lavage indicated an increased minimum surface tension, whereas lung histology showed perivascular edema and partial atelectasis in the vagotomized group. We conclude that stimulation of breathing and effective gas exchange are critically dependent on intact vagal nerves during the transition from fetal to neonatal life.

Animals↗
PubMed1998

Fictive gill and lung ventilation in the pre- and postmetamorphic tadpole brain stem.

The pattern of efferent neural activity recorded from the isolated brain stem preparation of the tadpole Rana catesbeiana was examined to characterize fictive gill and lung ventilations during ontogeny. In vitro recordings from cranial nerve (CN) roots V, VII, and X and spinal nerve (SN) root II of premetamorphic tadpoles showed a coordinated sequence of rhythmic bursts occurring in one of two patterns, pattern1, high-frequency, low-amplitude bursts lacking corresponding activity in SN II and pattern 2, low-frequency, high-amplitude bursts with coincident bursts in SN II. These two patterns corresponded to gill and lung ventilatory burst patterns, respectively, recorded from nerve roots of decerebrate, spontaneously breathing tadpoles. Similar patterns were observed in brain stem preparations from postmetamorphic tadpoles except that they showed a greater frequency of lung bursts and they expressed fictive gill ventilation in SN II. The laryngeal branch of the vagus (Xl) displayed efferent bursts in phase with gill and lung activity, suggesting fictive glottal constriction during gill ventilation and glottal dilation during lung ventilation. The fictive gill ventilatory cycle of pre- and postmetamorphic tadpoles was characterized by a rostral to caudal sequence of CN bursts. The fictive lung ventilatory pattern in the premetamorphic animal was initiated by augmenting CN VII discharge followed by synchronous bursts in CN V, X, SN II, and Xl. By contrast, postmetamorphic patterns of fictive lung ventilation were characterized by lung burst activity in SN II that preceded burst onset in CN V and followed the lead burst in CN VII. We conclude that recruitment and timing of pattern 1 and pattern 2 rhythmic bursts recorded in vitro closely resemble that recorded during spontaneous respiratory behavior, indicating that the two patterns are the neural equivalent of gill and lung ventilation, respectively. Further, fictive gill and lung ventilatory patterns in postmetamorphic tadpoles differ in burst onset latency from premetamorphic tadpole patterns and resemble fictive oropharyngeal and pulmonary burst cycles in adult frogs.

Aging↗
PubMed1997

Strychnine eliminates reciprocation and augmentation of respiratory bursts of the in vitro frog brainstem.

We have recorded rhythmic bursts of efferent action potentials from nerves of respiratory muscles in the frog (Rana pipiens), using a modified in vitro preparation, in which the brainstem lies in situ in the ventral half of the skull. The burst in the sternohyoid branch of the hypoglossal nerve (Hsh) was augmenting, and alternated with a relatively brief augmenting burst in the main branch of the hypoglossal nerve (Hm). The laryngeal branch of the vagus nerve (XI) displayed a biphasic burst, beginning before peak activity of Hsh and spanning the Hm burst. The spatio-temporal patterns of these bursts closely resemble those recorded from the same nerves in intact and in decerebrate frogs, indicating that the bursting rhythm of this in situ preparation constitutes fictive breathing. The nature of neurotransmission responsible for burst reciprocity and augmentation was investigated by applying the glycine receptor blocker, strychnine. Low levels of strychnine (1 and 5 M) increased the frequency of fictive breathing without changing the shape or timing of Hsh, Hm and XI bursts; at higher doses (10 and 20 M) the bursts in all nerves abruptly changed shape and timing to become synchronous and decrementing. The strychnine-induced changes were associated with the appearance of a prominent peak (10-20 Hz) on the spectral analysis of the nerve discharge, possibly indicating a fundamental change in neurogenesis of the respiratory pattern. We conclude that the burst augmentation and reciprocation discharge characteristics of fictive breathing in the frog require strychnine-sensitive inhibitory networks.

Animals↗
PubMed1997

Laryngeal motor control in frogs: role of vagal and laryngeal feedback.

Using decerebrate frogs (Rana catesbeiana), we investigated the role of vagal and laryngeal sensory feedback in controlling motor activation of the larynx. Vagal and laryngeal nerve afferents were activated by electrical stimulation of the intact vagal and laryngeal nerves. Pulmonary afferents were activated by lung inflation. Reflex responses were recorded by measuring efferent activity in the laryngeal branch of the vagus (Xl) and changes in glottal aperture. Two glottic closure reflexes were identified, one evoked by lung inflation or electrical stimulation of the main branch of the vagus (Xm), and the other by electrical stimulation of Xl. Lung inflation evoked a decrementing burst of Xl efferent activity and electrical stimulation of Xm resulted in a brief burst of Xl action potentials. Electrical stimulation of Xl evoked a triphasic mechanical response, an abrupt glottal constriction followed by glottal dilatation followed by a long-lasting glottal constriction. The first phase was inferred to be a direct (nonreflex) response to the stimulus, whereas the second and third represent reflex responses to the activation of laryngeal afferents. Intracellular recordings of membrane potential of vagal motoneurons of lung and nonlung types revealed EPSPs in both types of neurons evoked by stimulation of Xm or Xl, indicating activation of glottal dilator and constrictor motoneurons. In summary, we have identified two novel reflexes producing glottic closure, one stimulated by activation of pulmonary receptors and the other by laryngeal receptors. The former may be part of an inspiratory terminating reflex and the latter may represent an airway protective reflex.

Action Potentials↗