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Biomedical subjects

P Scheid

Publications and source records attributed to P Scheid.

At least 55 records · Page 3Linked to original sources

Respiratory response to positive inspiratory pressure in the cat: effects of CO2 and vagal integrity.

Effects of inspiratory pressure support (IPS) on respiration and activity of inspiratory muscles were tested in eight anesthetized cats by recording the diaphragmatic electromyogram (EMGdi) and respiratory variables at four levels of positive inspiratory airway pressure (5, 10, 15, and 20 cmH2O); onset of IPS was triggered by the inspiratory effort of the animal. When IPS was applied with room air (IPSAir) the respiratory frequency (f) was reduced compared with spontaneous breathing and the tidal volume (VT) was significantly increased, which resulted in a fall of arterial PCO2 (PaCO2) at IPS airway pressures (Paw) above 5 cmH2O. Despite this increase in VT, the amplitude of the integrated EMGdi (Adi) was reduced during IPS at all levels of Paw. When arterial hypocapnia is corrected by addition of CO2 to the inspirate, the values of VT at any given Paw were virtually identical with those during IPSAir, but IPS-mediated changes in f and Adi were smaller than those during IPSAir. IPS was also performed after bilateral vagotomy. Vagotomy itself caused VT and Adi to increase, and f to decrease, during spontaneous breathing. In comparison with the corresponding treatment before vagotomy, IPSAir led to a less severe reduction in Adi. As a result, VT was more enhanced and Paco2 was more reduced after vagotomy than before, both during spontaneous breathing and during IPSAir at all levels of Paw. When, however, isocapnia was restored with IPS with CO2 in the vagotomized animal, diaphragmatic activity and f became very similar to their values during spontaneous breathing, whereas VT remained elevated as a result of the high positive airway pressure. Our data suggest that in anesthetized cats IPS leads to a diminution of diaphragm activity and that this reduction can be entirely attributed to 1) the hypocapnia, resulting from increased VT, and 2) the stimulation of pulmonary vagal afferent fibers at positive airway pressure.

Animals↗

[Treatment of respiratory insufficiency in mucoviscidosis].

Cystic fibrosis respiratory disease leads to chronic respiratory insufficiency, pulmonary hypertension and cor pulmonale. Clinical evaluation must be helped by diurnal artérial gasometry and nocturnal saturation measure, especially in acute phase and during the weeks after respiratory infections. Treatment of hypoxemia is based on oxygenotherapy, but also on nasal nocturnal ventilation for patients waiting for a pulmonary transplantation. Association of them is able to conserve or enhance respiratory and nutritional status.

Chronic Disease↗

Activity-related pH changes in respiratory neurones and glial cells of cats.

Intracellular pH (pHi) and membrane potential (Em) were measured in vivo in expiratory neurones and glial cells in the medulla of anaesthetized cats using double-barrelled H(+)-sensitive microelectrodes. In glial cells, stimulation of spinal pathways evoked a depolarization of up to 12 mV amplitude and an increase of pHi (7.25 +/- 0.15) by maximally 0.1 pH unit. IN expiratory neurones, pHi (7.15 +/- 0.18) fell by up to 0.2 pH unit during inspiratory inhibition. In axons of expiratory neurones, pHi remained unaffected during rhythmic action potential discharges. We suggest that the glial alkalinization is due to activation of Na+/HCO3- cotransport, whereas the neuronal acidification is caused by efflux of HCO3- via receptor-coupled anion channels.

Animals↗

Pump for accurate mixing of three gas components with predetermined fractions.

A mixing pump that creates an accurate mixture of three gases at predetermined fractional ratios that can be set in steps of 10 ppm is described. A nearly continuous flow of each of the three component gases is produced by pistons driven by stepping motors; the gas mixture is forwarded by a fourth piston. The flow of each component gas is adjusted by the stepping frequency of the motor and a microcomputer system is used to adjust the three frequencies according to the desired fractional concentrations. The total flow of the gas mixture is adjustable between 0.1-500 ml/min and is nearly independent of the after-load. The accuracy of the pump was tested by mixing the respiratory gases, O2 and CO2, with various carrier gases (N, He or Ar) at various fractional ratios and total flow rates. The fractions of O2 and CO2 in the mixture were analysed with the Scholander technique. In the physiological range, the mixing error in the gas fractions was less than 4%. The pump is, thus, suited for producing calibration mixtures.

Carbon Dioxide↗

Ion-sensitive microelectrode system with short response time.

The measurement of changes in ion activity (e.g., pH) in neurons requires fine tip-sized double-barreled microelectrodes: one channel being equipped with an ion-selective liquid membrane, the other used for measurement of the membrane potential. The limited bandwidth and the differing transfer functions for electrical and ionic signals necessitate frequency response linearization networks to ensure that the output signal of the electrode is a faithful image of the input signal. We have developed a linearization network to ensure a rapid response time for ion-sensitive microelectrodes. To test the response characteristic we have developed a test system that allows the pH at the electrode tip to be changed within 1 ms. Application of these techniques to electrodes of 1 micron tip diameter results in a 90% response time to a pH step of approximately 60 ms and of approximately 2 ms with electrodes with 20 micron tip.

Electrophysiology↗

Respiratory response to inhaled CO2 during positive inspiratory pressure in humans.

To investigate ventilatory CO2 sensitivity during inspiratory pressure support (IPS), we administered inspiratory CO2 [fractional concn (FICO2) 0.01, 0.03, or 0.05] in eight normal subjects without (CTRL) or with (Pinsp) positive inspiratory airway pressure (5 or 10 cmH2O). At CTRL and low IPS, CO2 inhalation led to a significant increase in tidal volume (VT) with nearly identical slopes in the plot of VT vs. end-tidal PCO2. At the high IPS level, VT at FICO2 of 0 was significantly above the value at lower Pinsp and did not increase with CO2 unless FICO2 was elevated to > 0.03. There was very little effect of either Pinsp or FICO2 on respiratory frequency and respiratory timing. The data suggest that the CO2 sensitivity of ventilation is similar at low levels of IPS as during CTRL. However, at high levels of IPS, VT is determined largely by the passive inflation and, thus, independent of CO2. CO2 has to be elevated to increase the respiratory drive before VT becomes CO2 sensitive.

Administration, Inhalation↗

[Radon and primary bronchial cancer].

Radon is a natural radioactive gas, with worldwide distribution, deriving from uranium decay products, which can be inhaled, weather in mining condition (extraction and management of uranium ores) or in domestic condition (in some high risk homes or geographic areas). The main epidemiologic studies on uranium mining workers have all confirmed an excess in relative risk of primary lung cancer. Epidemiologic studies on indoor exposure suggest a role of radon in the genesis of a certain number of primary lung cancer, although these results remain controversial and need to be confirmed. An overview of the main actual problems related to this bronchial carcinogen is presented in this paper.

Animals↗

Transient ventilatory responses to endotoxin infusion in the cat are mediated by thromboxane A2.

We tested the hypothesis that ventilatory responses to endotoxin infusion in the anesthetized cat are mediated by thromboxane A2 (TxA2). Intravenous infusion of endotoxin (1.6 mg/kg of E. coli, strain 05:B55, delivered over 1 min) in six cats elicited increases in right ventricular blood pressure (Prv) and a transient systemic hypotension. These hemodynamic changes were accompanied by an abrupt apnea, followed by a transient period of rapid, shallow breathing, Cardiorespiratory changes coincided with large increases (> 10-fold) in the plasma concentration of TxB2, the stable metabolite of TxA2. These effects and the release of TxA2 did not occur if endotoxin was infused a second time into the same animal. In addition, animals that were pretreated with either indomethacin (n = 3; 3.0 mg/kg) or the TxA2 receptor antagonist, daltroban, (n = 4; 7.5 mg/kg) exhibited no change in Prv, arterial blood pressure, or respiration when given equivalent doses of endotoxin. We conclude that the release of TxA2 is responsible for the early pulmonary hypertension and rapid, shallow breathing observed during endotoxin infusion in the anesthetized cat. These TxA2-mediated responses are severe but transient in nature.

Animals↗

Depth profiles of pH and PO2 in the isolated brain stem-spinal cord of the neonatal rat.

We have measured depth profiles of extracellular pH (pHECR) and PO2 (PtO2) as well as the kinetics of changes of pHECR in the isolated brain stem-spinal cord preparation of the neonatal rat using pH and PO2 microelectrodes that entered from the ventral surface. When the preparation was superfused with control mock cerebrospinal fluid (Control mock CSF; pH = 7.5, PO2 = 630 Torr, PCO2 = 28 Torr, at 27 degrees C), the pH in the medulla diminished with a nearly constant gradient from the surface to a depth of about 1000 microns, the slope being about 0.1 pH unit per 100 microns. A similar gradient in the 200 to 300 microns of the CSF above the surface suggested existence of unstirred layers despite continuously flowing superfusate. The pH gradient in the spinal cord was somewhat smaller than that in the medulla. The PO2 gradients in both medulla and spinal cord were about 100 Torr per 100 microns from 200 microns above to 100 to 200 microns below the surface; PO2 reached zero at about 450 (medulla) to 600 microns (spinal cord). Although the preparation was anoxic and acidic except for a small layer below the surface, respiratory activity was recorded for several hours in C4 phrenic roots. The kinetics of changes in pHECF were recorded at 100 and 200 microns depth while rapidly replacing the control mock CSF by more acidic CSF, either with increased PCO2 ("Respiratory acidosis") or by adding fixed acid ("Metabolic acidosis"). The changes in pHECF were smaller than those in pHCSF, particularly during respiratory acidosis, as a result of the buffering of the brain tissue. Our results show the importance of superficial layers of the ventral medulla in producing respiratory rhythmicity; they further suggest that somewhat alkaline CSF (pH about 7.8) should be used in this preparation to ensure physiologic surface pH values despite unstirred surface layers.

Animals↗

Hypercapnia and medullary neurons in the isolated brain stem-spinal cord of the rat.

We have extracellularly recorded single neuron activity in the ventral medulla of the isolated brain stem-spinal cord preparation of the neonatal rat (37 preparations) in order to test their sensitivity to changes in CO2/H+. Search for neuronal activity was performed when the preparation was superfused with control mock CSF (equilibrated with 2% CO2, 90% O2 in N2; pH = 7.8 at 27 degrees C). Neurons, found down to about 500 microns from the surface, could be classified as R neurons when they showed rhythmic discharge in phase with phrenic activity, recorded from C4 ventral roots; or as Non-R neurons when they did not exhibit such phasic discharge. Among the 89 Non-R neurons, 20 responded to rapidly replacing the control CSF by hypercapnic CSF (8% CO2, 90% O2 in N2; pH = 7.2) with increased, 44 with reduced activity, while 25 did not respond to hypercapnia. Five Non-R neurons became phasic with respiration during hypercapnia. Of the 14 R neurons, 10 fired predominantly in expiration (R-E), 4 in inspiration (R-I). Only one R-E and two R-I neurons were excited by hypercapnia, the remaining were either inhibited or did not respond. Excited Non-R and R neurons were mainly encountered in rostral parts of those areas in the ventral medulla that have been reported as chemosensitive.

Animals↗

Effects of hypobaria on parabronchial gas exchange in normoxic and hypoxic ducks.

Cardio-respiratory parameters and air sac and blood gases were measured in the unrestrained, unanesthetized duck during exposure to normobaric (PB = 746 Torr) or hypobaric (PB = 253 Torr) normoxia (PIO2 = 143 Torr) and hypoxia (PIO2 = 41.5 Torr). Compared with normobaria at the same PIO2, hypobaria caused a statistically significant increase in ventilation during both normoxia and hypoxia, resulting in elevated PO2 and diminished PCO2 in the caudal thoracic and clavicular air sac, and in increased PaO2 and decreased PaCO2. Similarly, lactic acid production was elevated in hypobaria, and the resulting decrease in arterial pH may be responsible for the increase in ventilation. Despite these changes, there was no evidence for altered gas exchange efficiency during hypobaria. This suggests that no significant diffusion limitation is present in the air capillary gas phase in normobaria, that could have been diminished with hypobaria. It also suggests that the aerodynamic valving efficiency, present during inspiration at the level of the medioventral bronchi, is not affected by hypobaria. Although the mechanisms underlying the increased lactic acid production and ventilation are not understood, they may exert an advantageous effect on high altitude tolerance of the bird.

Animals↗

Effects of the thromboxane A2 mimetic, U46,619, on pulmonary vagal afferents in the cat.

Release of thromboxane A2 (TxA2) or infusion of the TxA2 mimetic U46,619 in the cat elicits pulmonary hypertension and rapid shallow breathing (Shams et al., Respir. Physiol. 71: 169-183, 1988). The vagus nerve mediates the observed respiratory, but not the circulatory, effects (Shams and Scheid, J. Appl. Physiol. 68: 2042-2046, 1990). To identify the type of lung vagal afferent fibers involved in this respiratory response to TxA2, we have recorded the functional single-unit activity and its response to infusion of U46,619 in fine strands of the vagus nerve in the artificially ventilated cat and rabbit. The fibers were classified as originating from slowly adapting (SAR) or rapidly adapting (RAR) stretch receptors by their response to sustained pulmonary inflation (intrapulmonary pressure of 20-25 cmH2O) or as C-fibers, by their response to a bolus injection of phenylbiguanide. C-fibers responded variably to lung inflation. U46,619 infusion caused only a small increase in SAR or RAR activity along with increases in end-inspiratory tracheal airway pressure (Paw), but evoked a marked increase in the firing rate of C-fibers, independent of their response to lung inflation. This increase in C-fiber activity was unrelated to the increase in Paw, which accompanied the infusion of U46,619. Since these responses remained the same after indomethacin they appear to be due to a direct action of U46,619, and not to be mediated by prostanoids that might be released by U46,619. These data suggest that C-fibers are indeed involved in the respiratory effects of TxA2. Since the effects exerted on C-fibers by U46,619 were unrelated to increased Paw, TxA2 is likely to stimulate the nerve endings directly, rather than via smooth muscle contraction. On the other hand, the small stimulating effect of U46,619 on SAR and RAR may be mediated by bronchoconstriction.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Respiratory response to positive and negative inspiratory pressure in humans.

To investigate the effect of positive or negative inspiratory pressure on respiration, eight subjects breathed, either without or with added external dead space (VD, 600 ml), through either added inspiratory laminar flow resistances (RES; peak inspiratory airway pressure, Pinsp, down to -9 cmH2O) or with inspiratory pressure support (IPS; Pinsp up to +10 cmH2O). IPS, triggered by the subject's inspiratory effort, provided positive airway pressure throughout inspiration, but allowed for attainment of the subject's own respiratory pattern. The following main results were obtained with IPS or RES relative to the control (no IPS, no RES): (1) with VD, IPS led to small, but significant, increases in tidal volume (VT), respiratory frequency (fR) and ventilation (VE), with no changes in inspiratory time (TI) or duty cycle (TI/TT). Mean inspiratory flow (VT/TI) increased, and mouth occlusion pressure 0.1 sec after onset of inspiration (P0.1) decreased significantly with IPS. The changes during RES were essentially in the opposite direction; (2) without VD, similar, but smaller effects were observed, and only the changes in VT/TI and P0.1 during IPS were significant; (3) highly significant decreases were observed during IPS in end-tidal PCO2 (PETCO2); on the average from 39.6 to 29.2 Torr without VD, and from 45.7 to 39.3 Torr with VD breathing. A small, but significant decrease in PETCO2 occurred also during RES with VD. We conclude that while resistive loading is nearly completely compensated with but small changes in PETCO2, inspiratory pressure support leads to marked hyperventilation, which is not effectively counteracted by central timing commands.

Adult↗

Airway anesthesia during positive and negative inspiratory pressure breathing in man.

We have measured the effects of airway anesthesia (aerosolized 5% lidocaine) on the respiratory pattern during positive or negative inspiratory pressure in 8 resting subjects. The subjects breathed through a 600 ml dead space (peak inspiratory airway pressure, Paw = -2 cmH2O) without or with negative (approx. -5 or -10 cmH2O) or positive (approx. +5 or +10 cmH2O) inspiratory pressure, provided by a laminar flow resistance or a positive pressure source, respectively. Control measurements were performed before and after measurements with airway anesthesia. Measurements included tidal volume, respiratory frequency, ventilation, inspiratory and expiratory duration, occlusion pressure (P0.1) and end-tidal PCO2. None of the parameters measured was significantly altered by airway anesthesia, which was effective in suppressing the cough reflex. We conclude that information from lung afferents that are suppressed with the elimination of the cough reflex is not important for the breathing pattern during resting ventilation with elevated tidal volume (dead space load) and with positive or negative inspiratory pressure.

Adult↗

Kinetics of the Root effect and of O2 exchange in whole blood of the eel.

Oxygen transfer kinetics in blood of the eel (Anguilla rostrata, A. anguilla) were measured spectrophotometrically in thin blood layers covered by Gore-Tex membranes, which allowed fast changes of the gas phase at the blood surface (Heidelberger and Reeves, 1990 J. Appl. Physiol. 68: 1854-1864). The following main results were obtained for A. rostrata (similar values were measured for A. anguilla): (1) step change in PO2 of the gas phase between 0 and 37 kPa at low PCO2 (0.19 kPa, blood pH, 8.1; 20 degrees C) yielded mean half times (t(on)) for O2 uptake of 7.1 msec, and for O2 release (t(off)), of 42.8 msec. Similar values were obtained at high PCO2 (19 kPa; blood pH, 6.9), indicating O2 kinetics to be independent of pH and PCO2; (2) decreasing the high PO2 from 37 to 14 kPa significantly prolonged oxygen uptake kinetics, but release kinetics were unaltered; (3) changing PCO2 from 0.19 to 19 kPa at constant high PO2 (37 kPa) resulted in a reduction of hemoglobin oxygen saturation (SO2) (Root-off reaction), with t(off) averaging 44.8 msec; likewise, changing PCO2 from 19 to 0.19 kPa increased SO2 with t(on) averaging 64.8 msec (Root-on reaction). As these half times comprise reactions at the hemoglobin molecule and conversion between CO2 and H(+)/HCO3-, the Root effect kinetics of the hemoglobin molecule appear to be even faster. It is concluded that the O2 exchange kinetics of eel blood are comparable with those of human blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗