Antioxidants Reverse Reduction of the Human Hypoxic Ventilatory Response by Subanesthetic Isoflurane

2005 ◽  
Vol 102 (4) ◽  
pp. 747-753 ◽  
Author(s):  
Luc J. Teppema ◽  
Raymonda R. Romberg ◽  
Albert Dahan
Keyword(s):  
Redox State ◽  
Direct Action ◽  
Upper Airway ◽  
The Body ◽  
Alpha Tocopherol ◽  
Hypoxic Response ◽  
Carotid Bodies ◽  
Intravenous Ascorbic Acid ◽  
End Tidal ◽  
Control Sham

Background In subanesthetic concentrations, volatile anesthetics reduce the acute hypoxic response (AHR), presumably by a direct action on the carotid bodies but by an unknown molecular mechanism. To examine a possible involvement of reactive oxygen species or changes in redox state in this inhibiting effect, the authors studied the effect of antioxidants on the isoflurane-induced reduction of the AHR in humans. Methods In 10 volunteers, the authors studied the effect of antioxidants (intravenous ascorbic acid and oral alpha-tocopherol) on the reduction by isoflurane (0.12% end-tidal concentration) of the AHR on a 3-min isocapnic hypoxic stimulus (hemoglobin oxygen saturation 86 +/- 4%). All subjects participated in three separate sessions in which the effects of the antioxidants (session 1), placebo (session 2), and sham isoflurane plus antioxidants (session 3) were tested on the (sham) isoflurane-induced effect on the AHR. Results Isoflurane reduced the acute hypoxic response from 0.82 +/- 0.41 l . min . % to 0.49 +/- 0.23 l . min . % and from 0.89 +/- 0.43 l . min . % to 0.48 +/- 0.28 l . min . % in sessions 1 and 2, respectively (mean +/- SD; P < 0.05 vs. control). This reduction of the AHR was completely reversed by antioxidants (AHR = 0.76 +/- 0.39 l . min . %; not significantly different from control, session 1) but not by placebo in session 2 (AHR = 0.50 +/- 0.30 l . min . %; P < 005 vs. control). Sham isoflurane or antioxidants per se had no effect on the hypoxic response. Conclusions The data indicate that isoflurane may depress the AHR by influencing the redox state of oxygen-sensing elements in the carotid bodies. This finding may have clinical implications for patients who are prone to recurrent hypoxic episodes, e.g., due to upper airway obstruction, in the postoperative period when low-dose isoflurane may persist in the body for some time.

Influence of reduced carotid body drive during sustained hypoxia on hypoxic depression of ventilation in humans

1996 ◽  
Vol 81 (2) ◽  
pp. 565-572 ◽  
Author(s):  
A. Dahan ◽  
D. Ward ◽  
M. van den Elsen ◽  
J. Temp ◽  
A. Berkenbosch
Keyword(s):  
Carotid Body ◽  
Hypoxic Exposure ◽  
Hypoxic Response ◽  
Air Breathing ◽  
Carotid Bodies ◽  
Delayed Recovery ◽  
End Tidal ◽  
Second Period ◽  
Sustained Hypoxia

To evaluate whether the intact hypoxic drive from the carotid bodies during sustained hypoxia is required for the generation of hypoxic depression of ventilation (VE), 16 volunteers were exposed to two consecutive periods of isocapnic hypoxia (first period 20 min; second period 5 min; end-tidal PO2 45 Torr) separated by 6 min of normoxia. In study A, saline was given. In study B, 3 micrograms.kg-1.min-1 i.v. dopamine (DA), a carotid body inhibitor, was given during the first hypoxic exposure followed by saline during normoxia and the second hypoxic exposure. In study C, 20 min of normoxia with DA preceded 6 min of normoxia and 5 min of hypoxia without DA. The first peak hypoxic VE (PHV) in study A was approximately 100% above normoxic VE. After 20 min of hypoxia, VE declined to 60% above normoxic VE. The second PHV in study A was only 60% of the first PHV. We relate this delayed recovery from hypoxia to "ongoing" effects of hypoxic depression. During DA infusion, the changes in VE due to sustained hypoxia were insignificant (study B). The second PHV in study B was not different from the PHV after air breathing in studies A and C. This indicates that the recovery from sustained hypoxia with a suppressed carotid body drive was complete within 6 min. Our results show that despite central hypoxia the absence of ventilatory changes during 20 min of isocapnic hypoxia due to intravenous DA prevented the generation of central hypoxic depression and the depression of a subsequent hypoxic response.

Upper airway muscle responsiveness to rising Pco 2 during NREM sleep

2000 ◽  
Vol 89 (4) ◽  
pp. 1275-1282 ◽  
Author(s):  
Giora Pillar ◽  
Atul Malhotra ◽  
Robert B. Fogel ◽  
Josee Beauregard ◽  
David I. Slamowitz ◽  
...  
Keyword(s):  
Muscle Activation ◽  
Slow Wave Sleep ◽  
Minute Ventilation ◽  
Upper Airway ◽  
Nrem Sleep ◽  
Dilator Muscle ◽  
Pharyngeal Muscles ◽  
Stage 2 Sleep ◽  
Significant Change ◽  
End Tidal

Although pharyngeal muscles respond robustly to increasing Pco 2 during wakefulness, the effect of hypercapnia on upper airway muscle activation during sleep has not been carefully assessed. This may be important, because it has been hypothesized that CO2-driven muscle activation may importantly stabilize the upper airway during stages 3 and 4 sleep. To test this hypothesis, we measured ventilation, airway resistance, genioglossus (GG) and tensor palatini (TP) electromyogram (EMG), plus end-tidal Pco 2(Pet CO2 ) in 18 subjects during wakefulness, stage 2, and slow-wave sleep (SWS). Responses of ventilation and muscle EMG to administered CO2(Pet CO2 = 6 Torr above the eupneic level) were also assessed during SWS ( n = 9) or stage 2 sleep ( n = 7). Pet CO2 increased spontaneously by 0.8 ± 0.1 Torr from stage 2 to SWS (from 43.3 ± 0.6 to 44.1 ± 0.5 Torr, P < 0.05), with no significant change in GG or TP EMG. Despite a significant increase in minute ventilation with induced hypercapnia (from 8.3 ± 0.1 to 11.9 ± 0.3 l/min in stage 2 and 8.6 ± 0.4 to 12.7 ± 0.4 l/min in SWS, P < 0.05 for both), there was no significant change in the GG or TP EMG. These data indicate that supraphysiological levels of Pet CO2 (50.4 ± 1.6 Torr in stage 2, and 50.4 ± 0.9 Torr in SWS) are not a major independent stimulus to pharyngeal dilator muscle activation during either SWS or stage 2 sleep. Thus hypercapnia-induced pharyngeal dilator muscle activation alone is unlikely to explain the paucity of sleep-disordered breathing events during SWS.

Phasic Genioglossus and Palatoglossus Muscle Activity during Recovery from Sevoflurane Anesthesia

2013 ◽  
Vol 119 (3) ◽  
pp. 562-568 ◽  
Author(s):  
Ilavajady Srinivasan ◽  
Samuel Strantzas ◽  
Mark W. Crawford
Keyword(s):  
Muscle Activity ◽  
Upper Airway ◽  
Dependent Manner ◽  
Sevoflurane Anesthesia ◽  
Phasic Activity ◽  
Similar Dose ◽  
Inhalational Anesthetic ◽  
Recovery From Anesthesia ◽  
End Tidal ◽  
Dose Dependent

Abstract Background: Inhalational anesthetic effects on upper airway muscle activity in children are largely unknown. The authors tested the hypothesis that phasic inspiratory genioglossus and palatoglossus activity increases during recovery from sevoflurane anesthesia in a dose-dependent manner in children. Methods: Sixteen children, aged 2.0 to 6.9 yr, scheduled for elective urological surgery were studied. Electromyogram recordings were acquired using intramuscular needle electrodes during spontaneous ventilation. After a 15-min period of equilibration, electromyogram activity was recorded over 30 s at each of three end-tidal concentrations, 1.5, 1.0, and 0.5 minimum alveolar concentration (MAC), administered in sequence. Results: Phasic genioglossus activity was noted in four children at 1.5 MAC, five at 1.0 MAC, and six children at 0.5 MAC sevoflurane. Phasic palatoglossus activity was noted in 4 children at 1.5 MAC, 6 at 1.0 MAC, and 10 children at 0.5 MAC sevoflurane. Both the proportion of children exhibiting phasic activity, and the magnitude of phasic activity increased during recovery from anesthesia. For the genioglossus, decreasing the depth of sevoflurane anesthesia from 1.5 to 1.0 MAC increased phasic activity by approximately 35% and a further decrease to 0.5 MAC more than doubled activity (median [range] at 1.5 and 0.5 MAC: 2.7 μV [0 to 4.0 μV] and 8.6 μV [3.2 to 17.6], respectively; P = 0.029). A similar dose-related increase was recorded at the palatoglossus (P = 0.0002). Conclusions: Genioglossus and palatoglossus activity increases during recovery from sevoflurane anesthesia in a dose-dependent manner over the clinical range of sevoflurane concentrations in children.

Chronic CO inhalation and carotid body catecholamines: testing of hypotheses

1989 ◽  
Vol 67 (1) ◽  
pp. 239-242 ◽  
Author(s):  
S. Lahiri ◽  
D. G. Penney ◽  
A. Mokashi ◽  
K. H. Albertine
Keyword(s):  
Blood Flow ◽  
Carotid Body ◽  
Direct Action ◽  
Systemic Effect ◽  
Hypoxic Hypoxia ◽  
Tissue Blood Flow ◽  
Catecholamine Content ◽  
Carotid Bodies ◽  
Significant Stimulation ◽  
Tissue Po2

The purpose of this study was twofold: one concerns carotid blood flow and tissue PO2 and the other the effect of chronic hypoxic hypoxia on enhanced catecholamine content. The rationale was that chronic CO inhalation would not mimic the effect of hypoxia on the carotid body if its tissue blood flow is sufficiently high to counteract the effect of CO on O2 delivery and, hence, on tissue PO2. The differential effects of CO on the carotid body and erythropoietin-producing tissue would also indicate that the effect of hypoxic hypoxia on the carotid body is the result of a direct action of a local low O2 stimulus rather than secondary to a systemic effect initiated by other O2-sensing tissues. To test these alternatives we studied the effects of chronic CO inhalation on carotid body catecholamine content and hematocrit in the rats, which were exposed to an inspired PCO of 0.4–0.5 Torr at an inspired PO2 of approximately 150 Torr for 22 days. The hematocrit of CO-exposed rats was 75 +/- 1.1% compared with 48 +/- 0.7% in controls. Dopamine and norepinephrine content of the carotid bodies (per pair) was 5.88 +/- 0.91 and 3.02 +/- 0.19 ng, respectively, in the CO-exposed rats compared with 6.20 +/- 1.0 and 3.29 +/- 0.6 ng, respectively, in the controls. Protein content of the carotid bodies (per pair) was 18.4 +/- 1.6 and 20.5 +/- 0.9 micrograms, respectively. Thus, despite a vigorous erythropoietic response, the CO-exposed rats failed to show any significant stimulation of carotid body in terms of the content of either catecholamine or protein. The results suggest that carotid body tissue PO2 is not compromised by moderate carboxyhemoglobinemia because of its high tissue blood flow and that the chronic effect of hypoxic hypoxia on carotid body is direct.

scholarly journals Dietary and pharmacological compounds altering intestinal calcium absorption in humans and animals

2015 ◽  
Vol 28 (2) ◽  
pp. 83-99 ◽  
Author(s):  
Vanessa Areco ◽  
María Angélica Rivoira ◽  
Valeria Rodriguez ◽  
Ana María Marchionatti ◽  
Agata Carpentieri ◽  
...  
Keyword(s):  
Health Professionals ◽  
Redox State ◽  
Calcium Absorption ◽  
Human Cancer ◽  
Protein Composition ◽  
Dietary Lipids ◽  
The Body ◽  
Renal Lithiasis ◽  
Important Health ◽  
Intestinal Ca Absorption

AbstractThe intestine is the only gate for the entry of Ca to the body in humans and mammals. The entrance of Ca occurs via paracellular and intracellular pathways. All steps of the latter pathway are regulated by calcitriol and by other hormones. Dietary and pharmacological compounds also modulate the intestinal Ca absorption process. Among them, dietary Ca and P are known to alter the lipid and protein composition of the brush-border and basolateral membranes and, consequently, Ca transport. Ca intakes are below the requirements recommended by health professionals in most countries, triggering important health problems. Chronic low Ca intake has been related to illness conditions such as osteoporosis, hypertension, renal lithiasis and incidences of human cancer. Carbohydrates, mainly lactose, and prebiotics have been described as positive modulators of intestinal Ca absorption. Apparently, high meat proteins increase intestinal Ca absorption while the effect of dietary lipids remains unclear. Pharmacological compounds such as menadione,dl-butionine-S,R-sulfoximine and ursodeoxycholic acid also modify intestinal Ca absorption as a consequence of altering the redox state of the epithelial cells. The paracellular pathway of intestinal Ca absorption is poorly known and is under present study in some laboratories. Another field that needs to be explored more intensively is the influence of the gene × diet interaction on intestinal Ca absorption. Health professionals should be aware of this knowledge in order to develop nutritional or medical strategies to stimulate the efficiency of intestinal Ca absorption and to prevent diseases.

scholarly journals Is mercury injected into the body for therapeutic purposes released into the spinal fluid?

1912 ◽  
Vol XIX (4) ◽  
pp. 803-813
Author(s):  
V. Lazarev
Keyword(s):  
Tuberculous Meningitis ◽  
Nervous Tissue ◽  
Direct Action ◽  
The Body ◽  
Spinal Fluid ◽  
Bile Pigment ◽  
Vascular Plexus ◽  
Points Of View ◽  
The Brain ◽  
Theoretical Side

Is mercury injected into the body excreted into the spinal fluid? This question occupied us with practical and theoretical points of view. On the practical side, we were interested in knowing how much we can count on the circulation of mercury in the spinal fluid and, therefore, on its direct action on the nervous tissue due to the communication of the perivascular (and pericellular) spaces with the sub-arachnoid. If mercury is released into the spinal fluid, it is necessary to search for the therapeutic effect (syphilis of the nervous system) of the drug that quickly and in large quantities passes into the spinal fluid. On the theoretical side, the issue of mercury release is of interest for solving the broader issue of the nature of spinal fluid in general. As is known, there is currently no agreement on this account. Is the spinal fluid transudate, the secretion of the vascular plexus epithelium or the sui generis lymph of the brain itself. In favor of the second1 views are inclined by Schultze, Imamura, Raubitschek, Molt, and others in favor of the last but Spina2 (also Lewandovsky and Blumenthal3. The first view is generally accepted. We thought that the saturation of blood with mercury, which happens with prolonged introduction of it into the body, should lead to the appearance of at least traces of it in the spinal fluid, if the latter is transudate. If the last secret, then apriori nothing can be predicted; extraction depends on the chemical and physical properties of the epithelium itself; the epithelium can secerne one substance and not pass another. The number of substances found so far in the spinal fluid when injected into the body is very limited. When the brain (and membranes) was normal, the substances introduced by the authors did not completely enter the spinal fluid. Widal, Monod4, Sicard was found in tuberculous meningitis iod when giving it during 2-3 days for 3-5 grams only in 3 cases. Guinon and Simon found only 1/2 cases of tuberculous meningitis; no iodine was found in cases of cerebrospinal meningitis. With uremia, Costaigne found iod and methylene blue. Sicard and Widal didnt find it. Gilbert and Castaigne found bile pigment in jaundice. Sicard denies. Archard Loeper5 did not find the lithium when it was injected into the blood. Regarding the fate of mercury introduced into the organism, there are no indications in the literature6.

Maturation of steady-state CO2 sensitivity in vagotomized anesthetized lambs

1992 ◽  
Vol 72 (4) ◽  
pp. 1255-1260 ◽  
Author(s):  
A. H. Jansen ◽  
S. Ioffe ◽  
V. Chernick
Keyword(s):  
Steady State ◽  
Test Procedure ◽  
Nerve Section ◽  
Co2 Response ◽  
Arterial Pco2 ◽  
Co2 Sensitivity ◽  
Carotid Bodies ◽  
Before And After ◽  
End Tidal ◽  
Respiratory Sensitivity

The maturation of the respiratory sensitivity to CO2 was studied in three groups of anesthetized (ketamine, acepromazine) lambs 2–3, 14–16, and 21–22 days old. The lambs were tracheostomized, vagotomized, paralyzed, and ventilated with 100% O2. Phrenic nerve activity served as the measure of respiration. The lambs were hyperventilated to apneic threshold, and end-tidal PCO2 was raised in 0.5% steps for 5–7 min each to a maximum 7–8% and then decreased in similar steps to apneic threshold. The sinus nerves were cut, and the CO2 test procedure was repeated. Phrenic activity during the last 2 min of every step change was analyzed. The CO2 sensitivity before and after sinus nerve section was determined as change in percent minute phrenic output per Torr change in arterial PCO2 from apneic threshold. Mean apneic thresholds (arterial PCO2) were not significantly different among the groups: 34.8 +/- 2.08, 32.7 +/- 2.08, and 34.7 +/- 2.25 (SE) Torr for 2- to 3-, 14- to 16-, and 21- to 22-day-old lambs, respectively. After sinus denervation, apneic thresholds were raised in all groups [39.9 +/- 2.08, 40.9 +/- 2.08, and 45.3 +/- 2.25 (SE) Torr, respectively] but were not different from each other. CO2 response slopes did not change with age before or after sinus nerve section. We conclude that carotid bodies contribute to the CO2 response during hyperoxia by affecting the apneic threshold but do not affect the steady-state CO2 sensitivity and the central chemoreceptors are functionally mature shortly after birth.

Arterial chemoreceptor input to respiratory hypoglossal motoneurons

1990 ◽  
Vol 69 (2) ◽  
pp. 700-709 ◽  
Author(s):  
S. W. Mifflin
Keyword(s):  
Membrane Potential ◽  
Upper Airway ◽  
Excitatory Input ◽  
Airway Patency ◽  
Hypoglossal Motoneurons ◽  
End Tidal ◽  
Carotid Body Chemoreceptors ◽  
Excitatory Drive ◽  
Arterial Chemoreceptor

To better understand the role of the arterial chemoreceptors in the regulation of upper airway patency at the level of the oropharynx, intracellular recordings were obtained from inspiratory hypoglossal motoneurons (IHMs), and the responses to selective activation of the carotid body chemoreceptors were examined. In pentobarbital-anesthetized, vagotomized, paralyzed, and artificially ventilated cats, chemoreceptor activation enhanced the inspiratory depolarization of membrane potential in 32 of 36 IHMs. This was manifested as an increase in either the amplitude (n = 13) or duration (n = 3) or an increase in both amplitude and duration (n = 16) of the inspiratory membrane potential depolarization. The amplitude and duration of the inspiratory membrane potential depolarization increased 98 +/- 15% (n = 29) and 78 +/- 13% (n = 19), respectively. Similar patterns of enhanced activity (increased duration and/or amplitude of membrane depolarization) were observed in five expiratory hypoglossal motoneurons (EHMs) after chemoreceptor activation. In 16 of the 32 IHMs, chemoreceptor activation also evoked changes in IHM membrane potential during expiration: enhanced post-inspiratory discharge (n = 6), expiratory depolarization/discharge (n = 6), and tonic depolarization/discharge, which persisted for several respiratory cycles (n = 4). The arterial chemoreceptors provide a powerful excitatory input to IHMs during both inspiration and expiration. This excitatory drive to IHMs and EHMs will aid in the maintenance of upper airway patency throughout the respiratory cycle during increases in end-tidal CO2.

Peripheral Chemoreflex Drive in Moderate-Intensity Exercise

1996 ◽  
Vol 21 (4) ◽  
pp. 285-300 ◽  
Author(s):  
Claudette M. St. Croix ◽  
David A. Cunningham ◽  
Donald H. Paterson ◽  
John M. Kowalchuk
Keyword(s):  
Peak Level ◽  
Cycle Ergometer ◽  
Open Loop ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Peripheral Chemoreceptor ◽  
Carotid Bodies ◽  
Ergometer Exercise ◽  
End Tidal ◽  
Peripheral Chemoreflex

The purpose of this study was to measure the contribution of the peripheral chemoreceptor (pRc) to [Formula: see text] during the steady-state of moderate-intensity cycle ergometer exercise using continuous hyperoxic suppression of pRc drive, while stabilizing the drive from the central chemoreceptor by clamping end-tidal PCO2 (PETCO2) at the peak level attained during the hyperoxic period of a poikilocapnic ride. In the isocapnic protocol, the PETCO2 was maintained at a constant level by a negative feedback, open loop system. Five subjects completed four repetitions of each of the poikilocapnic and isocapnic protocols. In the poikilocapnic protocol, [Formula: see text] declined following the step into hyperoxia and then began to increase, whereas the decline in [Formula: see text] was maintained in the isocapnic protocol. However, the mean decrease in [Formula: see text] was not significantly different between the poikilocapnic (16.1 ± 5.0%) and isocapnic (14.9 ± 4.4%) protocols. These results suggest that the declining phase of [Formula: see text] is fully complete before the secondary central stimulating actions of hyperoxia on [Formula: see text] and that the pRc contributes about 15% of the drive to breathe in moderate intensity exercise. Key words: ventilatory control, carotid bodies, hyperoxia

Translaryngeal jet ventilation and end-tidal PCO2 monitoring during varying degrees of upper airway obstruction

1991 ◽  
Vol 20 (11) ◽  
pp. 1193-1197 ◽  
Author(s):  
Kevin R Ward ◽  
James J Menegazzi ◽  
Donald M Yealy ◽  
Miroslav M Klain ◽  
Renee L Molner ◽  
...  
Keyword(s):  
Airway Obstruction ◽  
Upper Airway ◽  
Upper Airway Obstruction ◽  
Jet Ventilation ◽  
Pco2 Monitoring ◽  
End Tidal
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