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Biomedical subjects

A Dahan

Publications and source records attributed to A Dahan.

At least 55 records · Page 3Linked to original sources
PubMed1999

Sevoflurane-induced reduction of hypoxic drive is sex-independent.

BACKGROUND: Although the mu-opioid agonist morphine affects ventilatory control in men and women in different ways, no data exist regarding the influence of sex on the ventilatory effects of inhalational anesthetics. The authors compared the effect of sevoflurane on the ventilatory response to isocapnic hypoxia in healthy young men and women. METHODS: Breath-to-breath ventilatory responses to hypoxic steps (number of hypoxic steps, four-six; duration, 3 min; end-tidal oxygen tension, approximately 50 mmHg; end-tidal carbon dioxide tension clamped at approximately 4 mmHg above resting values) were assessed in nine men and nine women without and with low-dose sevoflurane (end-tidal concentration, 0.25%). The bispectral index of the electroencephalogram was measured concomitantly. RESULTS: Sevoflurane reduced the hypoxic ventilatory sensitivity significantly in both sexes (men: control, 0.62 +/- 0.17 vs. sevoflurane, 0.38 +/- 0.19 l x min(-1) x %(-1); women: control, 0.52 +/- 0.30 vs. sevoflurane, 0.34 +/- 0.15 l x min(-1) x %(-1)). Sevoflurane-induced reductions of the hypoxic responses were not different in the men and women. During sevoflurane inhalation, the bispectral index values decreased equally in men and women. CONCLUSION: In contrast to morphine, the influence of a low dose of the inhalational anesthetic sevoflurane on the ventilatory response to hypoxia is independent of sex.

Adult↗
PubMed1999

Sex differences in morphine-induced ventilatory depression reside within the peripheral chemoreflex loop.

BACKGROUND: This study gathers information in humans on the sites of sex-related differences in ventilatory depression caused by the mu-opioid receptor agonist morphine. METHODS: Experiments were performed in healthy young men (n = 9) and women (n = 7). Dynamic ventilatory responses to square-wave changes in end-tidal carbon dioxide tension (7.5-15 mmHg) and step decreases in end-tidal oxygen tension (step from 110 to 50 mmHg, duration of hypoxia 15 min) were obtained before and during morphine infusion (intravenous bolus dose 100 microg/kg, followed by 30 microg x kg(-1) x h(-1)). Each hypercapnic response was separated into a fast peripheral and slow central component, which yield central (Gc) and peripheral (Gp) carbon dioxide sensitivities. Values are mean +/- SD. RESULTS: In carbon dioxide studies in men, morphine reduced Gc from 1.61 +/- 0.33 to 1.23 +/- 0.12 l x min(-1) x mmHg(-1) (P < 0.05) without affecting Gp (control, 0.41 +/- 0.16 and morphine, 0.49 +/- 0.12 l x min(-1) x mmHg(-1), not significant). In carbon dioxide studies in women, morphine reduced Gc, from 1.51 +/- 0.74 to 1.17 +/- 0.52 l x min(-1) x mmHg(-1) (P < 0.05), and Gp, from 0.54 +/- 0.19 to 0.39 +/- 0.22 l x min(-1) x mmHg(-1) (P < 0.05). Morphine-induced changes in Gc were equal in men and women; changes in Gp were greater in women. In hypoxic studies, morphine depressed the hyperventilatory response at the initiation of hypoxia more in women than in men (0.54 +/- 0.23 vs. 0.26 +/- 0.34 l x min(-1) x %(-1), respectively; P < 0.05). The ventilatory response to sustained hypoxia (i/e., 15 min) did not differ between men and women. CONCLUSIONS: The data indicate the existence of sex differences in morphine-induced depression of responses mediated via the peripheral chemoreflex pathway, with more depression in women, but not of responses mediated via the central chemoreflex pathway. In men and women, morphine did not change the translation of the initial hyperventilatory response to short-term hypoxia into the secondary decrease in inspired minute ventilation (Vi) caused by sustained hypoxia.

Adolescent↗
PubMed1999

The dynamic relationship between end-tidal sevoflurane and isoflurane concentrations and bispectral index and spectral edge frequency of the electroencephalogram.

BACKGROUND: Inhalational anesthetics produce dose-dependent effects on electroencephalogram-derived parameters, such as 95% spectral edge frequency (SEF) and bispectral index (BIS). The authors analyzed the relationship between end-tidal sevoflurane and isoflurane concentrations (FET) and BIS and SEF and determined the speed of onset and offset of effect (t1/2k(e0)). METHODS: Twenty-four patients with American Society of Anesthesiologists physical status I or II were randomly assigned to receive anesthesia with sevoflurane or isoflurane. Several transitions between 0.5 and 1.5 minimum alveolar concentration were performed. BIS and SEF data were analyzed with a combination of an effect compartment and an inhibitory sigmoid Emax model, characterized by t1/2k(e0), the concentration at which 50% depression of the electroencephalogram parameters occurred (IC50), and shape parameters. Parameter values estimated are mean +/- SD. RESULTS: The model adequately described the FET-BIS relationship. Values for t1/2k(e0), derived from the BIS data, were 3.5 +/- 2.0 and 3.2 +/- 0.7 min for sevoflurane and isoflurane, respectively (NS). Equivalent values derived from SEF were 3.1 +/- 2.4 min (sevoflurane) and 2.3 +/- 1.2 min (isoflurane; NS). Values of t1/2k(e0) derived from the SEF were smaller than those from BIS (P < 0.05). IC50 values derived from the BIS were 1.14 +/- 0.31% (sevoflurane) and 0.60 +/- 0.11% (isoflurane; P < 0.05). CONCLUSIONS: The speed of onset and offset of anesthetic effect did not differ between isoflurane and sevoflurane; isoflurane was approximately twice as potent as sevoflurane. The greater values of t1/2k(e0) derived from the BIS data compared with those derived from the SEF data may be related to computational and physiologic delays.

Adolescent↗
PubMed1999

Isolation of microsatellite and RAPD markers flanking the Yr15 gene of wheat using NILs and bulked segregant analysis.

Microsatellite and random amplified polymorphic DNA (RAPD) primers were used to identify molecular markers linked to the Yr15 gene which confer resistance to stripe rust (Puccina striiformis Westend) in wheat. By using near isogenic lines (NILs) for the Yr15 gene and a F2 mapping population derived from crosses of these lines and phenotyped for resistance, we identified one microsatellite marker (GWM33) and one RAPD marker (OPA19(800)) linked to Yr15. Then, bulked segregant analysis was used in addition to the NILs to identify RAPD markers linked to the target gene. Using this approach, two RAPD markers linked to Yr15 were identified, one in coupling (UBC199(700)) and one in repulsion phase (UBC212(1200)). After MAPMAKER linkage analysis on the F2 population, the two closest markers were shown to be linked to Yr15 within a distance of about 12 cM. The recombination rates were recalculated using the maximum likelihood technique to take into account putative escaped individuals from the stripe rust resistance test and obtain unbiased distance estimates. As a result of this study, the stripe rust resistance gene Yr15 is surrounded by two flanking PCR markers, UBC199(700) and GWM33, at about 5 cM from each side.

Chromosome Mapping↗
PubMed1999

Acetazolamide and breathing. Does a clinical dose alter peripheral and central CO(2) sensitivity?

Improvement of blood gases with the carbonic anhydrase inhibitor acetazolamide in some patients with chronic obstructive pulmonary disease (COPD) is believed to result from an effect on the ventilatory control system. Carbonic anhydrase is ubiquitously present within the body, particularly in tissues involved in the control of breathing. Because low inhibitor concentrations are sufficient to block the enzyme in many tissues, it is of interest to document the effect of clinical doses of acetazolamide on the CO(2) sensitivities of the peripheral and central chemoreflex loops. In this study we measured the effect of chronic acetazolamide (250 mg by way of mouth, every 8 h during 3 days) on the dynamic ventilatory response to step changes in end-tidal PCO(2) in nine healthy volunteers. Data were analyzed using a two-compartment model comprising a fast peripheral and slow central compartment, enabling us to separate drug effects on the peripheral and central chemoreflex loops, respectively. Compared with placebo, acetazolamide did not change the CO(2) sensitivities and time constants of both chemoreflex loops. However, mean (+/- SD) resting ventilation increased from 12.22 +/- 2.41 to 14.01 +/- 1.85 L. min(-1), resulting in a decrease in end-tidal PCO(2) from 40.0 +/- 4.7 to 33.3 +/- 3.5 mm Hg. Base excess decreased from -0.08 +/- 1.20 to -7.48 +/- 2.07 mmol. L(-1), indicating metabolic acidosis and explaining a leftward shift of the CO(2) response curve by 7.3 mm Hg. Possible clinical implications of these results are discussed.

Acetazolamide↗
PubMed1998

Negative regulation of Ig gene rearrangement by a 150-bp transcriptional silencer.

We previously showed that the V-J intervening sequence of the chicken lambda immunoglobulin locus contains a strong silencer that acts both on transcription and rearrangement. We show here that the transcriptional silencer activity can be ascribed to a minimal 150-bp fragment. The rearrangement silencing activity was previously shown by the replacement of the V-J intervening sequence with a neutral DNA fragment that dramatically increased the rate of rearrangement of the transgene. Insertion of the minimal silencer in this neutral fragment is shown here to result in a marked decrease in rearrangement of the transgenic construct. Strikingly, deletion of 28 bp from the 150-bp fragment abolished most of the transcriptional silencing activity and had a similar effect on rearrangement. These results conclusively correlate the silencing activity on both rearrangement and transcription.

Animals↗
PubMed1998

Influence of 0.1 minimum alveolar concentration of sevoflurane, desflurane and isoflurane on dynamic ventilatory response to hypercapnia in humans.

To assess the effects and site of action of a sub-anaesthetic concentration of isoflurane, desflurane and sevoflurane (0.1 minimum alveolar concentration (MAC)) on respiratory control, we measured the ventilatory response to square wave changes in PE1CO2 against a background of normoxia. Using the computer steered "end-tidal forcing system", 2 min of steady state ventilation were followed by a step increase in PE1CO2 (1-1.5 kPa). This level was maintained for 8 min, followed by a step decrease to the original value for another 8 min. Each hypercapnic response was separated into a fast, peripheral component and a slow, central component, characterized by a time constant, carbon dioxide sensitivity, time delay and off-set. We studied 25 healthy volunteers; they performed 2-3 studies without and 2-3 studies during inhalation of the anaesthetic agent. Level of sedation was scored using a subjective seven-point scale from 0 (= alert and awake) to 6 (unrousable). In the isoflurane (16 subjects, 33 control, 37 drug studies) and sevoflurane (15 subjects, 40 control, 41 drug studies) studies, peripheral carbon dioxide sensitivity was reduced by approximately 45% and approximately 27% (ANOVA, P < 0.05 vs control), respectively, without affecting central carbon dioxide sensitivity or apnoeic threshold. In the desflurane study (16 subjects, 36 control, 37 drug studies), no significant effect was observed for any of the variables measured. A significant relation was observed between sedation score and change from control in central carbon dioxide sensitivities in the isoflurane and desflurane studies and in the change in the ratio peripheral carbon dioxide sensitivity over total carbon dioxide sensitivity in the sevoflurane studies. At the highest level of sedation observed (score 3-arousal state comparable with "light sleep"--in three subjects) these latter variables differed significantly from those in the other observed sedation levels (scores 1 and 2-a state of drowsiness). We conclude that 0.1 MAC of isoflurane and sevoflurane depressed the peripheral chemoreflex loop, without affecting the central chemoreflex loop. Desflurane at the same MAC showed no effect on peripheral and central carbon dioxide sensitivity. When the level of sedation was considered, our data suggested that at levels of sedation comparable with sleep, a depressive effect of all three anaesthetics was observed on the central chemoreflex loop.

Adult↗
PubMed1998

Sex-related differences in the influence of morphine on ventilatory control in humans.

BACKGROUND: Opiate agonists have different analgesic effects in male and female patients. The authors describe the influence of sex on the respiratory pharmacology of the mu-receptor agonist morphine. METHODS: The study was placebo-controlled, double-blind, and randomized. Steady-state ventilatory responses to carbon dioxide and responses to a step into hypoxia (duration, 3 min; oxygen saturation, approximately 82%; end-tidal carbon dioxide tension, 45 mmHg) were obtained before and during intravenous morphine or placebo administration (bolus dose of 100 microg/kg, followed by a continuous infusion of 30 microg x kg(-1) x h(-1)) in 12 men and 12 women. RESULTS: In women, morphine reduced the slope of the ventilatory response to carbon dioxide from 1.8 +/- 0.9 to 1.3 +/- 0.7 l x min(-1) x mmHg(-1) (mean +/- SD; P < 0.05), whereas in men there was no significant effect (control = 2.0 +/- 0.4 vs. morphine = 1.8 +/- 0.4 l x min(-1) x mmHg(-1)). Morphine had no effect on the apneic threshold in women (control = 33.8 +/- 3.8 vs. morphine = 35.3 +/- 5.3 mmHg), but caused an increase in men from 34.5 +/- 2.3 to 38.3 +/- 3 mmHg, P < 0.05). Morphine decreased hypoxic sensitivity in women from 1.0 +/- 0.5 l x min(-1) x %(-1) to 0.5 +/- 0.4 l x min(-1) x %(-1) (P < 0.05) but did not cause a decrease in men (control = 1.0 +/- 0.5 l x min(-1) x %(-1) vs. morphine = 0.9 +/- 0.5 l x min(-1) x %(-1)). Weight, lean body mass, body surface area, and calculated fat mass differed between the sexes, but their inclusion in the analysis as a covariate revealed no influence on the differences between men and women in morphine-induced changes. CONCLUSIONS: In both sexes, morphine affects ventilatory control. However, we observed quantitative and qualitative differences between men and women in the way morphine affected the ventilatory responses to carbon dioxide and oxygen. Possible mechanisms for the observed sex differences in the respiratory pharmacology of morphine are discussed.

Adolescent↗
PubMed1997

Expression of c-fos in the rat brainstem after exposure to hypoxia and to normoxic and hyperoxic hypercapnia.

In this study, Fos immunohistochemistry was used to map brainstem neuronal pathways activated during hypercapnia and hypoxia. Conscious rats were exposed to six different gas mixtures: (a) air; (b) 8% CO2 in air; (c) 10% CO2 in air; (d) 15% CO2 in air; (e) 15% CO2 + 60% O2, balance N2; (f) 9% O2, balance N2. Double-staining was performed to show the presence of tyrosine hydroxylase. Hypercapnia, in a dose-dependent way caused Fos expression in the following areas: caudal nucleus tractus solitarius (NTS), with few labeled A2 noradrenergic neurons; noradrenergic A1 cells and noncatecholaminergic neurons in the caudal ventrolateral medulla; raphe magnus and gigantocellular nucleus pars alpha (GiA); many noncatecholaminergic (and relatively few C1) neurons in the lateral paragigantocellular nucleus (PGCl), and in the retrotrapezoid nucleus (RTN); locus coeruleus (LC), external lateral parabrachial and Kölliker-Fuse nuclei, and A5 noradrenergic neurons at pontine level; and in caudal mesencephalon, the ventrolateral column of the periaqueductal gray (vlPAG). In most of these nuclei, hypoxia also induced Fos expression, albeit generally less than after hypercapnia. However, hypoxia did not cause labeling in RTN, juxtafacial PGCl, GiA, LC, or vlPAG. After normoxic hypercapnia, more labeled cells were present in NTS and PGCl than after hyperoxic hypercapnia. Part of the observed labeling could be caused by stress- or cardiovascular-related sequelae of hypoxia and hypercapnia. Possible implications for the neural control of breathing are also discussed, particularly with regard to the finding that several nuclei, not belonging to the classical brainstem respiratory centres, contained labeled cells.

Animals↗
PubMed1997

Influences of morphine on the ventilatory response to isocapnic hypoxia.

BACKGROUND: The ventilatory response to hypoxia is composed of the stimulatory activity from peripheral chemoreceptors and a depressant effect from within the central nervous system. Morphine induces respiratory depression by affecting the peripheral and central carbon dioxide chemoreflex loops. There are only few reports on its effect on the hypoxic response. Thus the authors assessed the effect of morphine on the isocapnic ventilatory response to hypoxia in eight cats anesthetized with alpha-chloralose-urethan and on the ventilatory carbon dioxide sensitivities of the central and peripheral chemoreflex loops. METHODS: The steady-state ventilatory responses to six levels of end-tidal oxygen tension (PO2) ranging from 375 to 45 mmHg were measured at constant end-tidal carbon dioxide tension (P[ET]CO2, 41 mmHg) before and after intravenous administration of morphine hydrochloride (0.15 mg/kg). Each oxygen response was fitted to an exponential function characterized by the hypoxic sensitivity and a shape parameter. The hypercapnic ventilatory responses, determined before and after administration of morphine hydrochloride, were separated into a slow central and a fast peripheral component characterized by a carbon dioxide sensitivity and a single offset B (apneic threshold). RESULTS: At constant P(ET)CO2, morphine decreased ventilation during hyperoxia from 1,260 +/- 140 ml/min to 530 +/- 110 ml/ min (P < 0.01). The hypoxic sensitivity and shape parameter did not differ from control. The ventilatory response to carbon dioxide was displaced to higher P(ET)CO2 levels, and the apneic threshold increased by 6 mmHg (P < 0.01). The central and peripheral carbon dioxide sensitivities decreased by about 30% (P < 0.01). Their ratio (peripheral carbon dioxide sensitivity:central carbon dioxide sensitivity) did not differ for the treatments (control = 0.165 +/- 0.105; morphine = 0.161 +/- 0.084). CONCLUSIONS: Morphine depresses ventilation at hyperoxia but does not depress the steady-state increase in ventilation due to hypoxia. The authors speculate that morphine reduces the central depressant effect of hypoxia and the peripheral carbon dioxide sensitivity at hyperoxia.

Analgesics, Opioid↗
PubMed1997

Influence of acute pain induced by activation of cutaneous nociceptors on ventilatory control.

BACKGROUND: Although many studies show that pain increases breathing, they give little information on the mechanism by which pain interacts with ventilatory control. The authors quantified the effect of experimentally induced acute pain from activation of cutaneous nociceptors on the ventilatory control system. METHODS: In eight volunteers, the influence of pain on various stimuli was assessed: room air breathing, normoxia (end-tidal pressure of carbon dioxide (PET(CO2)) clamped, normoxic and hyperoxic hypercapnia, acute hypoxia, and sustained hypoxia (duration, 15-18 min; end-tidal pressure of oxygen, approximately 53 mmHg). Noxious stimulation was administered in the form of a 1-Hz electric current applied to the skin over the tibial bone. RESULTS: While volunteers breathed room air, pain increased ventilation (V(I)) from 10.9 +/- 1.7 to 12.9 +/- 2.5 l/min(-1) (P < 0.05) and reduced PET(CO2) from 38.3 +/- 2.3 to 36.0 +/- 2.3 mmHg (P < 0.05). The increase in V(I) due to pain did not differ among the different stimuli. This resulted in a parallel leftward-shift of the V(I)-carbon dioxide response curve in normoxia and hyperoxia, and in a parallel shift to higher V(I) levels in acute and sustained hypoxia. CONCLUSIONS: These data indicate that acute cutaneous pain of moderate intensity interacted with the ventilatory control system without modifying the central and peripheral chemoreflex loop and the central modulation of the hypoxia-related output of the peripheral chemoreflex loop. Pain causes a chemoreflex-independent tonic ventilatory drive.

Adult↗
PubMed1996

Nerve grafting from spinal cord to spinal nerve: a microsurgical technique in cats.

A ventral surgical approach is described for the grafting of autologous saphenous nerves between the spinal cord and the avulsed C7 ventral root in the cat. To overcome serious blood loss from the epidural venous plexus, the cats were hyperventilated (end tidal PCO2 to about 23 mmHg) and controlled hypotension was induced (mean arterial pressure to about 60 mmHg). After selective avulsion of the ventral rootlets C7 the saphenous grafts were implanted into the spinal cord and coaptated to the avulsed spinal nerve. The combination of advanced anesthetic methods and microsurgical techniques appeared to be mandatory to achieve a low surgical mortality. Regenerated axons were retrogradely traced using retrograde horseradish peroxidase (HRP), and their functional recovery was evaluated by means of electrophysiological methods.

Anesthesia↗
PubMed1996

Slow ventilatory dynamics after isocapnic hypoxia and voluntary hyperventilation in humans: effects of isoflurane.

Short-term potentiation (STP) of breathing refers to respiratory activity that persists at termination of a primary stimulus and is not related just to the dynamics of chemoreceptors. In humans, STP is activated by brief episodes of hypoxia and voluntary hyperventilation (VHV). STP exerts a stabilizing influence on breathing pattern. To investigate the effects of a subanaesthetic concentration of isoflurane on STP, we studied recovery from mild and moderate hypoxic hyperpnoea and VHV. Experiments were performed in eight healthy volunteers. If necessary, subjects were aroused to maintain a state of wakefulness. In the hypoxic studies, a control study involved 1 min of isocapnic hypoxia (end-tidal PO2 (PE'O2 6.1) kPa) followed by sudden transition to normoxia. In the isoflurane studies, 1 min of mild hypoxia (Iso-1 study: PE'O2 6.2 kPa) and 1 min of moderate hypoxia (Iso-2 study: PE'O2 5.7 kPa) were followed by sudden transition to normoxia during inhalation of 0.1 minimum alveolar concentration (MAC) of isoflurane. PE'CO2 was maintained at 5.9 kPa. In the VHV study, ventilatory recovery from 1 min of normoxic VHV was monitored before and during inhalation of 0.1 MAC of isoflurane. Subjects performed multiple transitions in each study. In the hypoxic studies, peak ventilation after 1 min of hypoxic stimulation did not differ between treatments. The averaged responses reached normoxic baseline after 56.3 (SEM 10.7) s in the control study (n = 47 transitions), 18.0 (3.3) s in the Iso-1 study (n = 41; P < 0.05 vs control) and 15.3 (2.4) s in the Iso-2 study (n = 23; P < 0.05 vs control). In the VHV studies, VE at termination of VHV was not different from baseline after 36 s in the control study. An immediate reduction to less than baseline ventilation, lasting 24 s, was present in the isoflurane study. We believe that shortening of the time required to reach baseline in the hypoxic studies, and hypoventilation at cessation of VHV in the isoflurane studies, are related to the inability to activate STP of breathing via an effect of isoflurane on respiratory neurones in the brain stem. Increasing the stimulus intensity during isoflurane inhalation (Iso-2 study) did not (re)-activate STP.

Adult↗
PubMed1996

Mechanism of action of an epidural top-up in combined spinal epidural anesthesia.

The purpose of this study was to elucidate the mechanism of action by which an epidural top-up reinforces anesthesia in combined spinal epidural anesthesia. Thirty patients scheduled to undergo lower limb orthopedic surgery were randomly allocated to three groups of 10 patients each. In all patients, a 16-gauge Tuohy needle was introduced into the epidural space. Using the needle through needle technique, each patient received a subarachnoid injection of 10 mg plain bupivacaine 0.5% through a long 27-gauge Whitacre spinal needle introduced into the subarachnoid space through the Tuohy needle. After withdrawal of the spinal needle, an epidural catheter was introduced into the epidural space. After the maximum level of sensory block after the subarachnoid injection had been established, an epidural top-up with 10 mL bupivacaine 0.5% (Group 1) or 10 mL saline (Group 2) was administered; patients in Group 3 received no epidural top-up. The maximum level of sensory block was then assessed for an additional 30 min. After the epidural top-up the maximum level of sensory block increased significantly by 4.8 +/- 1.6 segments in Group 1 and 2.0 +/- 2.0 segments in Group 2. In Group 3 there was a nonsignificant increase of 0.3 +/- 0.5 segments. Intergroup comparisons showed that this increase in Group 1 was significant compared with those in Groups 2 and 3, and that the increase in Group 2 was significant compared with that in Group 3. We conclude that the mechanism of action by which an epidural top-up reinforces anesthesia in combined spinal epidural anesthesia can be explained partly by an epidural volume effect and partly by an effect of the local anesthetic itself.

Adolescent↗