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Biomedical subjects

M Zelter

Publications and source records attributed to M Zelter.

At least 19 recordsLinked to original sources

Effects of upper airway anaesthesia on respiratory-related evoked potentials in humans.

Cortical potentials evoked by mid-inspiratory occlusion arise from numerous receptors, many of which are probably within the upper airway. Their precise nature is not known. The aim of the current study was to improve knowledge of this by studying the effects of topical upper airway anaesthesia on respiratory-related evoked potentials. Respiratory-related evoked potentials were described through the averaging of electroencephalogram (EEG) epochs following mid-inspiratory occlusions (C3-CZ; C4-CZ). A total of 21 healthy volunteers (13 male, aged 22-52 yrs) were studied during mouth breathing, before and after topical upper airway anaesthesia (lidocaine). Moreover, 15 subjects were studied during nose breathing with and without anaesthesia. Six subjects were studied whilst inhaling L-menthol. Typical potentials were present in all the subjects, their components featuring normal amplitudes and latencies. The route of breathing and upper airway anaesthesia did not modify the EEG responses to inspiratory occlusions, qualitatively or quantitatively, during mouth or nose breathing. L-menthol had no effect. Upper airway receptors sensitive to topical anaesthesia are unlikely to contribute significantly to mid-inspiratory occlusion-evoked potentials. On the contrary, deeper receptors, such as joint and muscle receptors, could contribute dominantly to these potentials.

Administration, Inhalation↗

Facilitation of the diaphragm response to transcranial magnetic stimulation by increases in human respiratory drive.

The human respiratory neural drive has an automatic component (bulbospinal pathway) and a volitional component (corticospinal pathway). The aim of this study was to assess the effects of a hypercapnia-induced increase in the automatic respiratory drive on the function of the diaphragmatic corticospinal pathway as independently as possible of any other influence. Thirteen healthy volunteers breathed room air and then 5 and 7% hyperoxic CO2. Cervical (cms) and transcranial (tms) magnetic stimulations were performed during early inspiration and expiration. Transdiaphragmatic pressure (Pdi) and surface electromyogram of the diaphragm (DiEMG) and of the abductor pollicis brevis (apbEMG) were recorded in response to cms and tms. During inspiration, Pdi,cms was unaffected by CO2, but Pdi,tms increased significantly with 7% CO2. During expiration, Pdi,cms was significantly reduced by CO2, whereas Pdi,tms was preserved. DiEMG,tms latencies decreased significantly during early inspiration and expiration (air vs. 5% CO2 and air vs. 7% CO2). DiEMG,tms amplitude increased significantly in response to early expiration-tms (air vs. 5% CO2 and air vs. 7% CO2) but not in response to early inspiration-tms. DiEMG,cms latencies and amplitudes were not affected by CO2 whereas 7% CO2 significantly increased the apbEMG,cms latency. The apbEMG,tms vs. apbEMG,cms latency difference was unaffected by CO2. In conclusion, increasing the automatic drive to breathe facilitates the response of the diaphragm to tms, during both inspiration and expiration. This could allow the corticospinal drive to breathe to keep the capacity to modulate respiration in conditions under which the automatic respiratory control is stimulated.

Adaptation, Physiological↗

A phylogenetic hypothesis for the origin of hiccough.

The occurrence of hiccoughs (hiccups) is very widespread and yet their neuronal origin and physiological significance are still unresolved. Several hypotheses have been proposed. Here we consider a phylogenetic perspective, starting from the concept that the ventilatory central pattern generator of lower vertebrates provides the base upon which central pattern generators of higher vertebrates develop. Hiccoughs are characterized by glottal closure during inspiration and by early development in relation to lung ventilation. They are inhibited when the concentration of inhaled CO(2) is increased and they can be abolished by the drug baclofen (an agonist of the GABA(B) receptor). These properties are shared by ventilatory motor patterns of lower vertebrates, leading to the hypothesis that hiccough is the expression of archaic motor patterns and particularly the motor pattern of gill ventilation in bimodal breathers such as most frogs. A circuit that can generate hiccoughs may persist in mammals because it has permitted the development of pattern generators for other useful functions of the pharynx and chest wall muscles, such as suckling or eupneic breathing.

Animals↗

Unaltered respiratory-related evoked potentials after acute diaphragm dysfunction in humans.

Respiratory muscles play an important role in the origin of respiratory sensations. Data dissecting the role of the diaphragm and other inspiratory muscles are scarce. This study aimed to determine the impact of diaphragm dysfunction following inspiratory resistive loading on respiratory-related evoked potentials considered as a neurophysiological substrate of certain types of respiratory sensations. Altogether, nine subjects aged 25-50 yrs (six females) participated in the study. Transdiaphragmatic pressure output of cervical magnetic stimulation (with subdivision in oesophageal and gastric component), and respiratory-related evoked potentials (C3 and C4 derivations in the international 10-20 system) following mid-inspiratory occlusions were studied before and after an inspiratory-resistive loading challenge. Predominant diaphragm dysfunction was observed in seven subjects (average 28% reduction in transdiaphragmatic pressure, from 27.25-19.91 cmH2O, with increased oesophageal-to-gastric pressure ratio). The latencies and amplitudes of all the components of the respiratory-related evoked potentials were unchanged. The study concluded that predominant diaphragm fatigue does not affect respiratory-related evoked potentials.

Acute Disease↗

Expiratory flow limitation as a determinant of orthopnea in acute left heart failure.

OBJECTIVES: To assess the contribution of expiratory flow limitation (FL) in orthopnea during acute left heart failure (LHF). BACKGROUND: Orthopnea is typical of acute LHF, but its mechanisms are not completely understood. In other settings, such as chronic obstructive pulmonary disease, dyspnea correlates best with expiratory FL and can, therefore, be interpreted as, in part, the result of a hyperinflation-related increased load to the inspiratory muscles. As airway obstruction is common in acute LHF, postural FL could contribute to orthopnea. METHODS: Flow limitation was assessed during quiet breathing by applying a negative pressure at the mouth throughout tidal expiration (negative expiratory pressure [NEP]). Flow limitation was assumed when expiratory flow did not increase during NEP. Twelve patients with acute LHF aged 40-98 years were studied seated and supine and compared with 10 age-matched healthy subjects. RESULTS: Compared with controls, patients had rapid shallow breathing with slightly increased minute ventilation and mean inspiratory flow. Breathing pattern was not influenced by posture. Flow limitation was observed in four patients when seated and in nine patients when supine. In seven cases, FL was induced or aggravated by the supine position. This coincided with orthopnea in six cases. Only one out of the five patients without orthopnea had posture dependent FL. Control subjects did not exhibit FL in either position. CONCLUSIONS: Expiratory FL appears to be common in patients with acute LHF, particularly so when orthopnea is present. Its postural aggravation could contribute to LHF-related orthopnea.

Acute Disease↗

Diaphragmatic dysfunction and dyspnoea in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive disorder of unknown origin. Respiratory involvement is the principal cause of death, and dyspnoea is a major source of discomfort. In this study, diaphragm function is described and its relationship with dyspnoea examined in 48 ALS patients (32 male, age 26-80 yrs). The detailed neurological and respiratory evaluation (clinical examination, pulmonary function tests, static pressures, mouth twitch pressures (Pm,t), electromyographic responses to phrenic nerve stimulation and cortical magnetic stimulation were analysed after stratification according to dyspnoea. Dyspnoeic (group I) and nondyspnoeic (group II) patients were similar, bulbar signs being more frequent in group I. Vital capacity was lower in group I (mean+/-SD 67.9+/-22.7 versus 87.9+/-15.6% of the predicted value, p=0.0028), as were maximal static inspiratory pressure (41+/-24 versus 60+/-27% pred, p=0.0242) maximal static inspiratory pressure (18+/-11 versus 32+/-14% pred, p=0.0042), and Pm,t (3.71+/-2.5 versus 7.26+/-3.45 cmH2O, p=0.0011). Abdominal (Abd) paradox and respiratory pulse were frequent in group I (15 of 25 and 14 of 25) but absent or rare in group II (0 of 23 and four of 23) (p<0.05). The electromyographic responses to phrenic and cortical stimulation were generally abnormal in group I but subnormal in group II. Multivariate analysis selected only signs of diaphragm dysfunction (namely, Abd paradox and abnormal electromyographic responses) as significant predictors of dyspnoea. It is concluded that dyspnoea in amyotrophic lateral sclerosis patients should prompt diaphragm function tests.

Amyotrophic Lateral Sclerosis↗

Diaphragm and chest wall: assessment of the inspiratory pump with MR imaging-preliminary observations.

Magnetic resonance (MR) imaging of the thorax with three-dimensional (3D) reconstruction and functional quantification was evaluated as a tool for structure-function evaluation of chest-wall mechanics. Good agreement was found between the corresponding spirometric and MR imaging values of lung volumes. Fast MR imaging of the thorax with 3D reconstruction should improve the ability to evaluate the inspiratory pump in clinical and research investigations.

Adult↗

A computed tomographic scan assessment of endotracheal suctioning-induced bronchoconstriction in ventilated sheep.

This study was directed at assessing changes in bronchial cross-sectional surface areas (BCSA) and in respiratory resistance induced by endotracheal suctioning in nine anesthetized sheep. Cardiorespiratory parameters (Swan-Ganz catheter), respiratory resistance (inspiratory occlusion technique), BCSA, and lung aeration (computed tomography) were studied at baseline, during endotracheal suctioning, and after 20 consecutive hyperinflations. Measurements performed initially at an inspired oxygen fraction (FI(O(2))) of 0.3 were repeated at an FI(O(2)) of 1.0. At an FI(O(2)) of 0.3, endotracheal suctioning resulted in atelectasis, a reduction in BCSA of 29 +/- 23% (mean +/- SD), a decrease in arterial oxygen saturation from 95 +/- 3% to 87 +/- 12% (p = 0.02), an increase in venous admixture from 19 +/- 10% to 31 +/- 19% (p = 0. 006), and an increase in lung tissue resistance (DR(rs)) (p = 0. 0003). At an FI(O(2)) of 1.0, despite an extension of atelectasis and an increase in pulmonary shunt from 19 +/- 5% to 36 +/- 2% (p < 0.0001), arterial O(2) desaturation was prevented and BCSA decreased by only 7 +/- 32%. A recruitment maneuver after endotracheal suctioning entirely reversed the suctioning-induced increase in DR(rs) and atelectasis. In three lidocaine-pretreated sheep, the endotracheal suctioning-induced reduction of BCSA was entirely prevented. These data suggest that the endotracheal suctioning-induced decrease in BCSA is related to atelectasis and bronchoconstriction. Both effects can be reversed by hyperoxygenation maneuver before suctioning in combination with recruitment maneuver after suctioning.

Airway Resistance↗

Pulmonary blood flow distribution in stage 1 chronic obstructive pulmonary disease.

We investigated the hypothesis that lung blood flow distribution is modified in stage 1 chronic obstructive pulmonary disease (COPD). We compared patients with stage 1 COPD (n = 11) with restrictive patients with comparable blood gases (n = 7), to patients with low cardiac index with normal lungs (n = 11) and to control subjects (n = 11). Distribution of transit time (DTT) was computed by deconvolution from first pass radioactivity curves (albumin (99m)Tc) reconstructed from right and left ventricular regions of interest. Distribution descriptors, mean transit time (p < 0.05), standard deviation (p < 0.001), relative dispersion (p < 0.001), and kurtosis (p < 0.001) differed between groups (ANOVA). Cardiac index was the same in COPD and low CI groups but lower compared with normal subjects (p < 0.05). After normalization for cardiac output, the DTT of patients with COPD remained different from low CI and restrictive patients (p < 0.001). Therefore changes in DTT in patients with COPD compared with patients without COPD could not be explained on the basis of difference in cardiac output. Because P(O(2)), PC(O(2)), and pH were similar in COPD and restrictive groups, difference in distribution could not be explained either on the basis of blood gas data. We conclude that changes in DTT occurs in stage 1 COPD and cannot be explained by hypoxemia, hypercapnia, or acidosis alone but must relate to other structural or regulatory responses.

Adult↗

Effect of negative expiratory pressure on respiratory system flow resistance in awake snorers and nonsnorers.

In spontaneously breathing subjects, intrathoracic expiratory flow limitation can be detected by applying a negative expiratory pressure (NEP) at the mouth during tidal expiration. To assess whether NEP might increase upper airway resistance per se, the interrupter resistance of the respiratory system (Rint,rs) was computed with and without NEP by using the flow interruption technique in 12 awake healthy subjects, 6 nonsnorers (NS), and 6 nonapneic snorers (S). Expiratory flow (V) and Rint,rs were measured under control conditions with V increased voluntarily and during random application of brief (0.2-s) NEP pulses from -1 to -7 cmH(2)O, in both the seated and supine position. In NS, Rint,rs with spontaneous increase in V and with NEP was similar [3.10 +/- 0.19 and 3.30 +/- 0.18 cmH(2)O x l(-1) x s at spontaneous V of 1.0 +/- 0.01 l/s and at V of 1.1 +/- 0.07 l/s with NEP (-5 cmH(2)O), respectively]. In S, a marked increase in Rint,rs was found at all levels of NEP (P < 0.05). Rint,rs was 3.50 +/- 0.44 and 8.97 +/- 3.16 cmH(2)O x l(-1) x s at spontaneous V of 0.81 +/- 0.02 l/s and at V of 0.80 +/- 0.17 l/s with NEP (-5 cmH(2)O), respectively (P < 0.05). With NEP, Rint,rs was markedly higher in S than in NS both seated (F = 8.77; P < 0.01) and supine (F = 9.43; P < 0.01). In S, V increased much less with NEP than in NS and was sometimes lower than without NEP, especially in the supine position. This study indicates that during wakefulness nonapneic S have more collapsible upper airways than do NS, as reflected by the marked increase in Rint,rs with NEP. The latter leads occasionally to an actual decrease in V such as to invalidate the NEP method for detection of intrathoracic expiratory flow limitation.

Adult↗

Dynamic hyperinflation and flow limitation during methacholine-induced bronchoconstriction in asthma.

Although persistent activation of the inspiratory muscles and narrowing of the glottic aperture during expiration have been indicated as relevant mechanisms leading to dynamic hyperinflation in acute asthma, expiratory flow limitation (EFL) has recently been proposed as a possible triggering factor for increasing endexpiratory lung volume (EELV). To establish whether the attainment of maximal flow rate during tidal expiration could elicit dynamic elevation of EELV, breathing pattern, change in EELV by measuring inspiratory capacity (IC) and occurrence of EFL by the negative expiratory pressure (NEP) method were monitored in 10 stable asthmatic subjects during methacholine-induced, progressive bronchoconstriction in seated position. Change in dyspnoea was scored using the Borg scale. At maximum response forced expiratory volume in one second (FEV1) fell on average by 45+/-2% (p<0.001 versus control), while IC decreased 29+/-2%, (by 0.89+/-0.07 L, (p<0.01 versus control)). Only 2 subjects exhibited EFL at the end of methacholine challenge. In 7 subjects EELV started to increase before the occurrence of EFL. Dyspnoea, which increased from 0.2+/-0.1 to 5.5+/-1.0 (Borg scale) at maximum response (p<0.001), was significantly related to the level of bronchoconstriction as assessed by change in (delta)FEV1 (r=0.72; p<0.001) and to dynamic hyperinflation as measured by deltaIC (r=0.50; p<0.001). However, for both deltaFEV1 and deltaIC the slope of the relationship with increasing dyspnoea was highly variable among the subjects. It is concluded that in acute methacholine-induced bronchoconstriction, dynamic hyperinflation may occur in the absence of expiratory flow limitation and that expiratory flow limitation does not represent the triggering factor to generate dynamic hyperinflation. In these circumstances, dyspnoea appears to be related to the increase in end-expiratory lung volume and not to the onset of expiratory flow limitation.

Asthma↗

Effects of catecholamines on the pulmonary venous bed in sheep.

OBJECTIVE: To assess the effects of various catecholaminergic agents on pulmonary venous tone. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: Physiology laboratory of a university hospital. SUBJECTS: Thirty anesthetized, mechanically ventilated adult sheep. INTERVENTIONS: Four groups of six animals received 1-hr infusions of norepinephrine (0.5 microg/kg/min), epinephrine (0.5 microg/kg/ min), dopamine (10 microg/kg/min), or dobutamine (10 microg/kg/min). MEASUREMENTS AND MAIN RESULTS: A 7-Fr pulmonary artery catheter was placed in a proximal location to measure cardiac output and pressure in a large pulmonary vein (Ppw) after balloon inflation. Another catheter wedged in a small pulmonary artery measured pressure in a small pulmonary vein (Pdw). A third catheter measured left atrial pressure (PLA ). This method was able to detect the pulmonary venoconstrictive effects of histamine in a separate group of six animals. Pdw-PLA increased from a mean of 2.0+/-1.7 to 3.0+/-1.5 (SD) cm H2O (p < .01), 2.3+/-1.6 to 4.4+/-1.3 cm H2O (p < .01), and 1.7+/-1.0 to 3.5+/-2.2 cm H2O (p < .05) with norepinephrine, epinephrine, and dopamine, respectively. All of these drugs increased Pdw-Ppw, but only norepinephrine and epinephrine increased Ppw-PLA . No change in either pressure difference was observed with dobutamine. Elevation of cardiac output alone could not account for these findings since the increase in cardiac output induced by fluid infusion did not change the pressure differences. CONCLUSION: Norepinephrine, epinephrine, and dopamine at doses commonly used in humans increase pulmonary venous tone in sheep.

Animals↗

Application of negative expiratory pressure during expiration and activity of genioglossus in humans.

The application of negative expiratory pressure (NEP) at end expiration has been shown to cause reflex-mediated activation of the genioglossus muscle in awake humans. To test whether a reflex contraction of pharyngeal dilator muscles also occurs in response to NEP applied in early expiration, the effect on genioglossus muscle reflex activity of NEP pulses of 500 ms, given 0.2 s after the onset of expiration and during the end-expiratory pause, was assessed in 10 normal awake subjects at rest. The raw and integrated surface electromyogram of the genioglossus (EMGgg) was recorded with airflow and mouth pressure under control conditions and with NEP ranging from -3 to -10 cmH2O. Intraoral EMGgg was also recorded under the same experimental conditions in two subjects. The application of NEP at the end-expiratory pause elicited a consistent reflex response of EMGgg in seven subjects with a mean latency of 68 +/- 5 ms. In contrast, when NEP was applied at the onset of expiration, EMGgg reflex activity was invariably observed in only one subject. No relationship was found between steady increase or abrupt fall in expiratory flow and the presence or the absence of a reflex activity of genioglossus during sudden application of NEP at the beginning of expiration. Our results show that a reflex activity of genioglossus is elicited much more commonly during application of NEP at the end rather than at the onset of expiration. These findings also suggest that when NEP is applied in early expiration to detect intrathoracic flow limitation the absence of upper airways narrowing does not imply the occurrence of a reflex-mediated activation of genioglossus and vice versa.

Adult↗