Biomedical subjects

D Gozal

Publications and source records attributed to D Gozal.

At least 109 records · Page 6Linked to original sources

PubMed1996

Optical imaging of the ventral medullary surface of developing kittens during ventilatory challenges.

We used large-array optical recording procedures to examine maturation of regional neural activity within the ventral medullary surface (VMS) of anaesthetized kittens during graded hypercapnic and hypoxic challenges. The VMS was exposed through a ventral surgical approach in 10, 20, 30, and 45-day-old kittens and in adult cats under sodium pentobarbital anaesthesia. Arterial pressure, costal diaphragmatic EMG, and ECG were continuously monitored. A coherent image conduit with 12 mu fibre resolution was attached to a charge-coupled-device camera and positioned over the VMS. Reflected 660 nm light was digitized continuously at 2-s intervals during a baseline period, hyperoxic hypercapnia, (3, 5, and 10% CO2 in O2), and poikylocapnic hypoxia (6%, 9%, and 12% O2 in N2), and recovery. Sixty to seventy-five images within each epoch were averaged, and subtracted from baseline. Regional differences within the image were determined by ANOVA procedures (alpha = 0.05). During hypercapnia, an overall decrease in neural activity (increase in scattered light) occurred, which was marginally age-dependent. By 30 days, regional bidirectional reflectance changes in response to CO2 emerged in a small proportion of animals, and were similar to adult responses. Hypoxia induced a dose- and age-dependent decrease in overall scattered light. Transient "on" and "off" responses were common under both ventilatory stimuli. In 20-30-day kittens, marked rebound responses in reflectance accompanied cessation of hypoxic stimuli; such patterns were absent at other ages. At 30 days, a caudal-rostral bidirectionality in response to mild hypoxia (12% O2) began to emerge in a subset of animals. We conclude that dose-dependent response to ventilatory stimuli occur in the VMS at all post-natal ages of the kitten; however, in hypoxia, the magnitude of the overall reflectance changes is diminished relative to adult patterns. Rebound responses to hypoxia are present at particular ages, and older kittens begin to show a topographical organization of neural activation.

Analysis of Variance↗

PubMed1996

Imaging of VMS activity during blood pressure challenges in awake and anesthetized goats.

We examined scattered-light changes in a rostral ventral medullary surface (VMS) area from five goats after blood pressure challenges during waking and halothane anesthesia. Reflected 660-nm images were digitized at 1/s after baseline; intravenous saline; 5, 10, or 15 micrograms/kg phenylephrine administration; or sodium nitroprusside infusion sufficient to lower blood pressure by 50%. Phenylephrine elicited a dose-dependent, blood pressure elevation during both states and a substantial transient reflectance increase (interpreted as activity decline) during anesthesia, but only a minimal, long-latency, slow-reflectance decrease activity increase) during waking. Sodium nitroprusside elicited lowering of blood pressure and decreased reflectance in the rostral site during anesthesia. The magnitude of the reflectance change to depressor challenge increased 30%, and the onset latency shortened during waking. Isolated regions of enhanced reflectance changes appeared during both challenges. Activity in this rostral VMS site differentially responds to blood pressure elevation or lowering, and state markedly alters the responses. We speculate that VMS responses to depressor challenge represent reflex activation of respiratory regions.

Anesthesia, General↗

PubMed1996

Effect of nitric oxide synthase inhibition on cardiorespiratory responses in the conscious rat.

Nitric oxide synthase (NOS) blockade was used to test the cardioventilatory responses to hypercapnia and hypoxia in freely behaving animals. Chronically instrumented adult Sprague-Dawley rats were studied before and after intravenous administration of either 100 mg/kg of NG-nitro-L-arginine methyl ester (L-NAME), a nonspecific NOS blocker, or 10 mg/kg of S-methyl-L-thiocitrulline (SMTC), a selective neural NOS inhibitor. L-NAME injection induced sustained blood pressure (BP) elevation with transient tachycardia and increased minute ventilation (VE), which returned to baseline within minutes. SMTC elicited similar, although transient, BP increases; however, heart rate and VE decreased. L-NAME and SMTC did not modify overall steady-state hypercapnic responses. In control conditions, hypoxia induced early VE increases with further VE enhancements at 30 min. L-NAME increased the early VE response to 10% O2 but induced late VE reductions in hypoxia. SMTC did not change early VE responses but induced marked reductions in the later VE hypoxic responses. In control animals, hypoxia induced a significant heart rate increase. This increase was absent during the early response after SMTC and was followed in both L-NAME- and SMTC-treated animals by significant heart rate reductions to values below room air. Similarly, the sustained BP response to hypoxia in control animals was absent after administration of NOS inhibitors. These findings suggest that NOS activity exerts excitatory influences on respiration and cardiac chronotropy and sustained vasomotor tone during hypoxia. We speculate that NOS-mediated mechanisms may play an important role in hypoxia-induced ventilatory roll-off during wakefulness.

Animals↗

PubMed1996

Characterization and developmental aspects of anoxia-induced gasping in the rat.

With increasing postnatal age, mammals display diminished tolerances for prolonged exposures to severe oxygen deprivation. Similarly, duration and efficiency of gasping, a unique mechanism for enhancing survival after anoxia-induced apnea, are also affected by postnatal age. We hypothesized that maturational patterns of anoxia-induced gasping may encompass more than a single monophasic phenomenon. Each of the putative phases of the gasping response may underlie unique characteristics which could be of relevance to survival capability. To study these issues, adult rats and rat pups at 2-3, 5, 10, 15, and 25 days of age underwent anoxic exposures with 100% N2 in a barometric chamber. In pups aged < 25 days but not thereafter, following an age-dependent period of central apnea, an initial gasping phase characterized by vigorous and frequent periodic bursts of a large inspiratory effort preceded and followed by expiration excursions emerged (phase I). This phase was followed by a period of relative respiratory silence of variable duration with occasional, interspersed phase I-like gasps (phase II). Finally, a third phase easily recognized by the onset of frequent inspiratory-only gasping efforts developed (phase III). The amplitude of phase III inspiratory gasps progressively diminished until their complete cessation. Although overlap between gasping phases was present, a marked age dependency in both duration and gasping frequency within each phase occurred. We conclude that anoxia-induced gasping responses in rat pups < 25 days old are triphasic in nature, exhibit defined phase-locked periodicities and respiratory effort patterns, and undergo significant maturation.

Aging↗

PubMed1996

Arousal and cardiorespiratory responses to hypoxia in Prader-Willi syndrome.

Ventilatory responses to peripheral chemoreceptor stimuli are absent in patients with Prader-Willi syndrome (PWS) during wakefulness. Because arousal from sleep after rapidly developing hypoxia may require intact peripheral chemoreceptor function, we hypothesized that blunted hypoxic arousal responses during sleep Stage 3/4 would be present in PWS. Thirteen patients with PWS (mean age, 23.4 +/- 3.7 +/- SEM yr; 46% male; body mass index [BMI], 28.9 +/- 1.6 kg/m2) and 11 matched control subjects (mean age 28.0 +/- 5.4 yr; 54% male; BMI, 28.8 +/- 3.1 kg/m2) were studied. An abrupt decrease in inspired O2 tension to 80 mm Hg was introduced until arousal occurred or for a maximum of 3 min. One of the 13 patients with PWS and seven of the 11 control subjects were aroused by the hypoxic challenge (p < 0.02). During hypoxia, heart rate increased by 9 +/- 2% in the PWS group versus 22 +/- 4% in the control group (p < 0.005). Respiratory rate did not change in the PWS group (4 +/- 2%; p = NS), but it increased by 13 +/- 2% in the control group (p < 0.02). We conclude that abnormal arousal and cardiorespiratory responses to hypoxia are frequent in PWS. We postulate that intact peripheral chemoreceptor function is an important component underlying arousal mechanisms to rapidly developing hypoxia during sleep.

Adult↗

PubMed1996

Effects of overnight supplemental oxygen in obstructive sleep apnea in children.

Supplemental oxygen during sleep may be useful as a temporary palliative treatment in children with obstructive sleep apnea syndrome (OSAS) associated with significant hypoxemia. However, supplemental O2 may also blunt hypoxic ventilatory drive and worsen ventilation. To assess the safety of the use of supplemental O2 in children with OSAS, we studied 16 children ages 2-8 (mean: 4.28 +/- 2.88 yr) with OSAS secondary to adenotonsillar hypertrophy. Patients underwent two overnight polysomnograms within 1 mo, one on room air (RA) and one while receiving supplemental O2 via nasal cannula titrated by 1/4 lpm increments to achieve SpO2 > 95% during the first hour of sleep. Oxygenation measurements were significantly improved during supplemental O2 nights (average SpO2 increased from 89.5 +/- 4.8% on RA to 97.7 +/- 1.8% on supplemental O2 [p < 0.00001]) while alveolar ventilation remained unchanged (PETCO2 > 50 mm Hg: 3.6 +/- 8.9% total sleep time on RA and 3.3 +/- 6.3% total sleep time on supplemental O2 [p = NS]). Supplemental O2 significantly reduced hypopnea density, obstructive apnea index, and paradoxical breathing. The density and average duration of central apneas remained unchanged. In addition, supplemental O2 increased the percentage of REM sleep time and decreased the number of microarousals. We conclude that supplemental O2 might be a safe and beneficial temporary treatment in children with OSAS.

Age Factors↗

PubMed1996

Ventilatory responses to passive leg motion in children with congenital central hypoventilation syndrome.

During exercise, children with congenital central hypoventilation syndrome (CCHS) demonstrate coupling of VE to exercise load, despite the absence of a VE response to changes in FICO2. To assess the effect of movement on VE, we studied six CCHS patients and six matched controls during passive motion in a motor-driven ergocycle at pedaling frequencies (PF) of 6 to 60 rpm. VE, VO2, VCO2, VT, heart rate, respiratory rate, SPO2, and PETCO2 were measured. During steady-state conditions, VE was constant at PF of 0 to 30 rpm, but increased at PF > or = 40 rpm in both controls and CCHS patients (p < 0.005). The increase in respiratory rate in CCHS patients was greater than in controls (p < 0.05) whereas VT increased similarly in both groups. At 60 rpm, VO2 increased in both groups, but VE/VO2 and VE/VCO2 increased in the CCHS patients and remained constant in the controls (P < 0.03; p < 0.04). From PF of 0 to 60, PETCO2 decreased from 47 +/- 7 to 41 +/- 6 mm Hg in the CCHS patients (p < 0.001) but remained unchanged in the controls (38 +/- 3 mm Hg; p = NS). An analysis of on-transient responses at 60 rpm revealed that VE increased immediately with the first breath after onset of motion in both groups, and that comparable differences in ventilatory patterns persisted in the two groups. We conclude that passive leg motion at PF > or = 40 increases VE in both CCHS patients and controls. In controls, VE was tightly coupled to VO2 and VCO2. However, in CCHS patients, passive leg motion elicited normalization of PETCO2.

Adolescent↗

PubMed1996

Longitudinal assessment of hypercapnic ventilatory drive after tracheotomy in a patient with the Prader-Willi syndrome.

The clinical course and changes in hypercapnic ventilatory drive over time were serially assessed before and after tracheostomy placement in a 14 year old, morbidly obese female patient with Prader-Willi syndrome, severe obstructive sleep apnoea, and obesity-hypoventilation syndrome. A tracheostomy became necessary after supplemental oxygen and continuous positive airway pressure (CPAP) had failed to improve the severity of nocturnal hypoventilation. Continued improvement in the slope to rebreathing hyperoxic hypercapnia occurred from 2-10 weeks after tracheotomy in conjunction with night-time bilevel pressure ventilation, and remained unchanged thereafter. In contrast, increases in mean resting minute ventilation at an end-tidal carbon dioxide tension (PET,CO2) of 8 kPa (60 mmHg) were documented even after 30 weeks. This case study illustrates the time-frame of dynamic ventilatory changes occurring after removal of upper airway resistance and normalization of nocturnal alveolar ventilation.

Adolescent↗

PubMed1996

[Anesthetic problems of epidermolysis bullosa dystrophica. Apropos of a case].

Epidermolysis bullosa is a group of hereditary diseases of the skin that may also involve mucous membranes, particularly of the oropharynx and oesophagus. The common primary feature is the formation of blisters following even trivial trauma. During the management of anaesthesia, it is critical that trauma to the skin and mucous membranes be avoided or minimized in these patients. We report the case of a 3-year-old child who had two surgeries and discuss the anaesthetic implications of this disease.

Anesthesia, General↗

PubMed1995

Identification of human brain regions underlying responses to resistive inspiratory loading with functional magnetic resonance imaging.

Compensatory ventilatory responses to increased inspiratory loading are essential for adequate breathing regulation in a number of pulmonary diseases; however, the human brain sites mediating such responses are unknown. Midsagittal and axial images were acquired in 11 healthy volunteers during unloaded and loaded (30 cmH2O; 1 cmH2O = 98 Pa) inspiratory breathing, by using functional magnetic resonance imaging (fMRI) strategies (1.5-tesla MR; repetition time, 72 msec; echo time, 45 msec; flip angle, 30 degrees; field of view, 26 cm; slice thickness, 5 mm; number of excitations, 1; matrix, 128 x 256). Digital image subtractions and region of interest analyses revealed significantly increased fMRI signal intensity in discrete areas of the ventral and dorsal pons, interpeduncular nucleus, basal forebrain, putamen, and cerebellar regions. Upon load withdrawal, certain regions displayed a rapid fMRI signal off-transient, while in others, a slower fMRI signal decay emerged. Sustained loading elicited slow decreases in fMRI signal across activated regions, while second application of an identical load resulted in smaller signal increases compared to initial signal responses (P < 0.001). A moderate inspiratory load is associated with consistent regional activation of discrete brain locations; certain of these regions have been implicated in mediation of loaded breathing in animal models. We speculate that temporal changes in fMRI signal may indicate respiratory after-discharge and/or habituation phenomena.

Adult↗

PubMed1995

Rostral ventral medullary surface activity during hypercapnic challenges in awake and anesthetized goats.

Regions within the rostral ventral medullary surface (RVMS) play an important role in cardiorespiratory responses to CO2 during anesthesia. Activity within a RVMS area, in which local cooling elicited marked ventilatory and blood pressure reductions, was measured as 660 nm scattered light changes in 5 goats following 5% CO2 challenges during waking and anesthetic states. During wakefulness, hypercapnia elicited a substantial, short latency transient (1-1.5 min) activity increase, followed by a sustained decrease. Stimulus cessation elicited a large and rapid off-transient activity increase which persisted for approximately 20 min. In contrast, during halothane anesthesia, the initial activation was absent, and the later activity decline and off-response were much reduced. We conclude that biphasic RVMS activity responses emerge to CO2 stimulation, and are state-dependent.

Administration, Inhalation↗

PubMed1995

Hyperoxia during recovery from consecutive anaerobic exercises in the sickle cell trait.

The sickle cell trait (HbAS) does not affect anaerobic exercise performance. However, lower blood lactate concentrations ([La-]) are consistently found during repeated anaerobic exercise in HbAS, and could be related to type of recovery. To study this, on three different occasions 17 HbAS and 17 matched control athletes (HbAA) underwent a series of three maximal cycle exercise tests of approximately 2-min duration, separated by 10-min recovery periods of rest, breathing either room air (P) or 100% oxygen (H), or of light pedaling (A). In all tests, work performed, heart rate, blood hematocrit, and [La-] were measured. Despite similar evolution of performance in each series of three anaerobic exercises, significantly lower [La-] were consistently found in HbAS in P and A, compared to HbAA (P < 0.0001). However, in H, similar [La-] was found in HbAS and HbAA. Higher mean heart rates were consistently measured in HbAS at exhaustion, and during the first 4 min of recovery, these differences being unrelated to type of recovery. We conclude that type of recovery does not influence subsequent performance in HbAS or HbAA. We speculate that improved regional oxygen availability in exercising muscle is associated with marked modification of lactate kinetics in highly trained HbAS, but not in similarly fit HbAA athletes.

Adult↗

PubMed1995

Neonatal urinary uric acid/creatinine [correction of ceratinine] ratio as an additional marker of perinatal asphyxia.

UNLABELLED: The diagnosis and evaluation of perinatal asphyxia can be problematic and objective means of assessing its severity are lacking. To study the validity of urinary uric acid as a marker of the degree of perinatal asphyxia, the ratio of urinary uric acid to creatinine (UA/Cr) in urine specimens obtained after birth was measured in two groups of infants. Eighteen term infants with Apgar scores < or = 5 at 5 min and/or an umbilical cord blood pH < or = 7.2, and a base deficit > or = 12 meq/l were compared to 50 healthy controls. The severity of the perinatal asphyxia was determined by using an ASPHYXIA SCORE. The UA/Cr was higher in the asphyxiated group when compared to controls. (2.06 +/- 1.12, vs. 0.64 +/- 0.48; P < 0.001). Within the perinatal asphyxia group, a significant correlation was found between the UA/Cr ratio and the asphyxia score. (r = 0.86, P < 0.01). CONCLUSION: Infants with perinatal asphyxia have a significantly higher urinary UA/Cr ratio. This may be used as an indicator of the severity of perinatal asphyxia.

Asphyxia Neonatorum↗

PubMed1995

Ventral medullary surface responses to hypoxic and hyperoxic transient ventilatory challenges in the cat.

Carotid body afferent contributions to activity of the intermediate area of the ventral medullary surface (IVMS) following transient hypoxia and hyperoxia were examined in 6 spontaneously breathing, pentobarbital-anesthetized cats. Two tidal breaths of 100% N2, 100% O2, or room air, were randomly administered before and after carotid sinus denervation (CSD). Images of scattered light from the IVMS showed that activity increased with hypoxia (10.1 +/- 2.4%), and decreased with hyperoxia (4.8 +/- 1.8%). CSD significantly increased the magnitude and delayed the onset of the hypoxic response, but reversed the initial component of the hyperoxic response. We conclude that carotid body afferents modulate the magnitude and timing of IVMS responses to transient respiratory challenges.

Animals↗

PubMed1995

A quantitative physiologic model of blood oxygenation for functional magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Variations in venous deoxyhemoglobin levels in response to neuronal activation represent a complex interplay between focal changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and regional metabolism. The authors present a mathematic model that characterizes the response of venous oxygenation to changes in these variables. METHODS: Using a mass balance approach, the equations for a simple input-output model are derived and solved using Matlab. Changes in blood oxygenation are related to available results from functional magnetic resonance imaging experiments. RESULTS: Increases in CBF produce declines in oxygen extraction fraction and venous deoxyhemoglobin according to Fick's law, and are quantitatively in agreement with available magnetic resonance and positron-emission tomography data. A flow-volume envelope defines the changes in CBF relative to CBV. CONCLUSIONS: It is possible to obtain a quantitative understanding of changes in blood oxygenation and to relate these changes to the observed dynamics of magnetic resonance signal change in the setting of functional stimulation.

Algorithms↗

PubMed1995

Pressor-induced responses of the cat ventral medullary surface.

We examined ventral medullary surface activity using light reflectance procedures after blood pressure alterations induced by phenylephrine or sodium nitroprusside in 23 pentobarbital sodium-anesthetized cats. Images of reflected 660-nm light were collected and digitized at 1- to 3-s intervals after baseline and intravenous saline, 5-40 micrograms/kg phenylephrine, or sodium nitroprusside infusion. Carotid sinus nerve denervation (CSD) and bilateral vagotomy were performed in five and three animals, respectively, and challenges were repeated. Phenylephrine elicited a dose-dependent transient blood pressure elevation and reflectance increase (interpreted as activity decline) over the entire ventral medullary surface examined. The increase consisted of an initial rapid transient component, peaking at 45 s, and a 3- to 5-min recovery. CSD enhanced, and vagotomy substantially reduced, the initial transient response to phenylephrine. Sodium nitroprusside-induced lowering of blood pressure was associated with decreased reflectance in rostral sites and increased reflectance in caudal regions. CSD abolished a late component and diminished amplitude of an initial rapidly rising component of changes induced by nitroprusside, a decline further accentuated by addition of vagotomy.

Animals↗

PubMed1995

Ventilatory responses to repeated short hypercapnic challenges.

In early phases of respiratory disease, patients are more likely to experience intermittent hypercapnia than a continuous increase in PCO2. The effect of intermittent arterial PCO2 elevation on subsequent breathing patterns is unclear. To examine this issue, a series of six ventilatory challenges (CH1-CH6), consisting of 2 min of breathing 5% CO2 in O2, followed by 5 min in room air (RA) were performed in 10 naive healthy subjects (age 12-39 yr). Minute ventilation (VE) increased from 11.9 +/- 1.0 (SE) l/min in RA to 27.6 +/- 3.0 l/min in 5% CO2 (P < 0.0005) in each of the six hypercapnic challenges. Respiratory rate increased from 21.3 +/- 2.6 breaths/min on RA to 29.6 +/- 3.9 breaths/min during CH1 (P < 0.05). However, respiratory rate consistently decreased with successive CO2 challenges (CH6: 21.5 +/- 2.6 breaths/min; P < 0.02). Thus, maintenance of VE was achieved by gradual increases in tidal volume with each of the first four consecutive CO2 challenges (CH1: 1.05 +/- 0.09 liters; CH4: 1.44 +/- 0.13 liters; P < 0.002). Similarly, the ratio of tidal volume to inspiratory time increased from CH1 (1.16 +/- 0.16 l/s) to CH6 (1.57 +/- 0.21 l/s; P < 0.001). These changes in ventilatory strategy were not observed when RA recovery periods were extended to 15 min in five subjects. We conclude that during repeated short hypercapnic challenges similar levels of VE are achieved. However, increased mean inspiratory flows are generated to maintain VE. We speculate that intermittent hypercapnia either modifies central controller gain or induces a long-term modulatory effect to account for the progressive changes in ventilatory components.

Administration, Inhalation↗

PubMed1995

Ventilatory response to consecutive short hypercapnic challenges in children with obstructive sleep apnea.

In healthy adults, a ventilatory pattern characterized by progressively increased tidal volume (VT), and decreased respiratory rate (RR) accompany repeated short hypercapnic ventilatory challenges, while minute ventilation (VE) remains constant. We hypothesized that the peculiar ventilatory pattern seen in adults would be blunted in children with obstructive sleep apnea syndrome (OSAS) who undergo comparable intermittent or chronic alveolar PCO2 elevation. We measured ventilatory responses to five challenges of 2-min duration (C1-C5) with 5% CO2 in O2, separated by 5-min room-air breathing intervals (R1-R4), in nine children with OSAS and in eight age-, sex-, and body mass index-matched controls. In all children, CO2 significantly increased VE when compared with baseline conditions (22.3 +/- 2.2 vs. 9.5 +/- 0.9 (SE) l/min; P < 0.001). In control subjects, progressive VT increases from 0.67 +/- 0.10 liter in C1 to 0.92 +/- 0.13 liter in C5 occurred (P < 0.01), whereas RR decreased from 33.9 +/- 5.1 breaths/min in C1 to 27.8 +/- 3.7 breaths/min in C5 (P < 0.02), resulting in VE increases across CO2 challenges (22.3 +/- 4.9 l/min in C1 vs. 25.1 +/- 5.0 l/min in C5; P < 0.005). The RR decrease was primarily related to progressive prolongation of expiratory time (TE) (1.1 +/- 0.1 s in C1 to 1.5 +/- 0.2 s in C5; P < 0.002). In contrast, VT, RR, and TE did not change in a consistent fashion in OSAS patients with repeated CO2 challenges (OSAS vs. control: P < 0.0001). Furthermore, in OSAS, VE was similar with repeated challenges (22.4 +/- 2.2 1/min in C1 vs. 23.9 +/- 1.9 l/min; P = not significant), such that changes in VE over time significantly differed in OSAS and controls (P < 0.001). We conclude that healthy children modify their ventilatory strategy to repeated hypercapnia. We speculate that in OSAS these mechanisms are already fully implemented because of recurrent alveolar hypoventilation accompanying increased upper airway resistance, leading to blunted temporal trends of ventilatory response.

Adolescent↗