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Biomedical subjects

A Guz

Publications and source records attributed to A Guz.

At least 55 records · Page 3Linked to original sources
PubMed1995

Modulation by "central" PCO2 of the response to carotid body stimulation in man.

We describe a method to assess the effects of PCO2, around and below eucapnia, on the neuromuscular ventilatory response to a standard peripheral chemoreceptor stimulus. Subjects were "passively" hyperventilated (without respiratory muscle activity), at a constant level of ventilation. Stimuli (3-7 breaths N2) were delivered over a range of steady-state PETCO2 (25-43 mmHg). Stimuli during hypocapnia were coupled with a transient increase in FICO2 so that the stimulus to the peripheral chemoreceptors was always "hypoxia at eucapnia". Responses to the stimuli (quantified from the reduction in peak inflation pressure and the magnitude of the evoked diaphragm electromyographic activity) decreased in a graded manner as steady-state PETCO2 fell, disappearing at 7.5 mmHg below eucapnia. Carotid body chemoreceptor recordings from two anaesthetised cats, indicated that the peak firing rate during such stimuli was independent of steady-state PETCO2. The results suggest that the central sensitivity to a peripheral chemoreceptor input may be modulated by changes in steady-state PCO2 around eucapnia and during mild hypocapnia.

Adult↗
PubMed1995

Is voluntary control of breathing impaired in patients with chronic obstructive pulmonary disease?

1. To assess whether voluntary control of breathing is impaired in patients with chronic obstructive pulmonary disease, a group of such patients performed a tracking task, requiring volitional control of respiratory muscles. 2. Eight patients (mean age 60 years; mean ratio of forced expiratory volume in 1 s to forced vital capacity = 31%) took part in the study. Five of the seven patients in whom blood gas measurements were made were mildly hypoxaemic (PaO2 = 53-71 mmHg), and one of these was hypercapnic (PaCO2 = 55 mmHg). Each subject performed a compensatory ventilatory tracking task using a tracking system which comprised a fixed target displayed on a monitor screen and a cursor moving in a line bisecting the target. The position of the cursor was perturbed by a forcing function and patients were required to keep the cursor on the target by breathing in and out of a spirometer. 3. To allow for any non-specific deficiency in motor control, patients performed a similar manual tracking task, using their dominant arm to move a joystick. As a control group, 11 healthy subjects (mean age 58 years; mean ratio of forced expiratory volume in 1 s to forced vital capacity = 77%) underwent an identical experimental protocol. 4. Motor control performances were measured in terms of the error between the target position and the subject's positioning of the cursor. Indices of performance were the root mean square of the error and the averages of the zero errors (i.e. end expiration/arm movement towards the trunk) and the peak errors (i.e. end inspiration/arm movement from the trunk).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Changes in total pulmonary resistance and PCO2 between wakefulness and sleep in normal human subjects.

We investigated the possible role of an increase in total pulmonary resistance in the sleep-related hypoventilation that occurs in healthy subjects. Eight nonsnoring volunteers were studied during quiet wakefulness and stage IV sleep. Airflow was measured via a nasal mask with a low dead space, and breathing pattern, end-tidal PCO2 (PETCO2), and a continuous estimate of total pulmonary resistance were estimated. From wakefulness to sleep, mean inspiratory resistance increased from 5.5 +/- 2.4 (SD) to 8.1 +/- 4.3 cmH2O.l-1.s, PETCO2 increase from 38.7 +/- 3.0 to 40.7 +/- 3.5 Torr, and ventilation decreased from 7.12 +/- 1.15 to 6.47 +/- 1.68 l/min. In five of the eight subjects, low levels of continuous positive airway pressure were applied during stage IV sleep to reverse any increase in resistance. In these subjects, continuous positive airway pressure reduced mean inspiratory resistance from 9.3 +/- 4.3 +/- 3.0 cmH2O.l-1.s but had little effect on mean PETCO2 (from 39.8 +/- 4.0 to 39.6 +/- 4.0 Torr) and mean ventilation (from 6.79 +/- 1.93 to 6.91 +/- 1.80 l/min). These findings suggest that in nonsnoring subjects reductions in alveolar ventilation cannot be accounted for by an increase in airway resistance.

Adult↗
PubMed1995

Central and reflex neural control of genioglossus in subjects who underwent laryngectomy.

Inspiratory activation of the genioglossus (GG) may occur by central drive or as a reflex to negative airway pressure. To distinguish between these, we studied seven laryngectomy patients who breathe via tracheal stomas. Negative pressure stimuli (-15 and -25 cmH2O for 500 ms) were applied 1) at functional residual capacity and 2) during early inspiration via (i) the upper airway (UA) and (ii) the tracheal stoma. Intraoral surface GG electromyogram was quantified, as described previously (R. L. Horner, J. A. Innes, K. Murphy, and A. Guz, J. Physiol. Lond. 436: 15-29, 1991). Phasic GG activity was also measured from an integrated electromyogram during spontaneous and inspiratory loaded breathing. Reflex GG activation occurred with negative UA pressure both at functional residual capacity and during inspiration (P < 0.001), but pressure stimuli at the stoma caused no significant activation (P = 0.07). Phasic inspiratory activation occurred in four patients at rest and in all seven patients during inspiratory loading (P < 0.02). These patients demonstrate 1) reflex activation of the GG by negative UA pressure without airflow or respiratory effort and 2) central inspiratory GG activation that is not mediated by negative airway pressure.

Aged↗
PubMed1995

Lipocortin-1 distribution in bronchoalveolar lavage from healthy human lung: effect of prednisolone.

Lipocortin-1 (LC-1; annexin-1) may mediate some anti-inflammatory actions of the glucocorticoids, probably after binding to specific cell surface binding sites. We have quantified LC-1 levels in bronchoalveolar lavage (BAL) fluid and cells collected from seven healthy volunteers before and after 7 days of treatment with an oral glucocorticoid, prednisolone (30 mg/day). Extracellular BAL LC-1 was higher and cellular LC-1 was lower after prednisolone than before [extracellular: before, median 98 ng/mg albumin (range 48-350 ng/mg albumin); after, 236 ng/mg albumin (19-414 ng/mg albumin); P < 0.05. Cellular: before, 23.3 ng/10(6) cells (14.6-26.9 ng/10(6) cells); after, 18.0 ng/10(6) cells (122-268 ng/10(6) cells); P < 0.05]. The distribution of LC-1 within BAL cells ex vivo (cell surface = 25%, cytosol = 50%, membrane = 25%) was unaffected by prednisolone treatment. However, in adherent cells that had been cultured for 4 h, 70-80% of the LC-1 was on the cell surface. In summary, prednisolone appears to promote cellular release of LC-1. The difference in distribution of cellular LC-1 in BAL cells ex vivo and in vitro may reflect adherence and/or activation.

Adult↗
PubMed1994

The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans.

The present study was designed to determine the effect of sleep on reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in human subjects. Intra-oral bipolar surface electrodes were used to record genioglossus electromyogram (EMG) responses to 500 ms duration pressure stimuli of 0 and -25 cmH2O applied, via a face-mask, in four normal subjects. Stimuli were applied during early inspiration in wakefulness and in periods of non-rapid-eye-movement (non-REM) sleep, defined by electroencephalographic (EEG) criteria. The rectified and integrated EMG responses to repeated interventions were bin averaged for the 0 and -25 cmH2O stimuli applied in wakefulness and sleep. Response latency was defined as the time when the EMG activity significantly increased above prestimulus levels. Response magnitude was quantified as the in ratio of the EMG activity for an 80 ms post-stimulus period to an 80 ms prestimulus period; data from after the subject's voluntary reaction time for tongue protrusion (range, 150-230 ms) were not analysed. Application of the -25 cmH2O stimuli caused genioglossus muscle activation in wakefulness and sleep, but in all subjects response magnitude was reduced in sleep (mean decrease, 61%; range, 52-82%; P = 0.011, Student's paired t test). In addition, response latency was increased in sleep in each subject (mean latency awake, 38 ms; range, 30-50 ms; mean latency asleep, 75 ms; range, 40-110 ms; P = 0.072, Student's paired t test). Application of the -25 cmH2O stimuli caused arousal from sleep on 90% occasions, but in all cases the reflex genioglossus muscle responses (maximum latency, 110 ms) always proceeded any sign of EEG arousal (mean time to arousal, 643 ms; range, 424-760 ms). These results show that non-REM sleep attenuates reflex genioglossus muscle activation by stimuli of negative airway pressure. Attenuation of this reflex by sleep may impair the ability of the upper airway to defend itself from suction collapse by negative pressures generated during inspiration; this may have implications for the pathogenesis of obstructive sleep apnoea.

Adult↗
PubMed1994

Red-edge excitation fluorescence spectroscopy of proteins in reversed micelles.

The dependence of fluorescence emission maxima of L-tryptophan and single-tryptophan-containing proteins (ribonuclease T1, melittin, and parvalbumin) on excitation wavelength has been studied in reversed micelle systems of sodium bis(2-ethyl-1-oxyl) sulfosuccinate (AOT). No effect of fluorescence maximum shift for different excitation wavelengths is observed for ribonuclease T1, in which a single tryptophan residue is located in the nonrelaxating, nonpolar protein interior. L-Tryptophan and the rest of the studied proteins, which contain single tryptophan residues exposed to the solvent, exhibit the dipolar relaxational processes of partly immobilized water molecules in micelles. This effect depends on the molar H2O/AOT ratio. Circular dichroism measurements prove that there have been no structural changes of the studied proteins in micellar systems. The results provide information about dynamic relaxational processes in proteins.

Animals↗
PubMed1994

Excursion-volume relation of the right hemidiaphragm measured by ultrasonography and respiratory airflow measurements.

BACKGROUND: Although real time ultrasonography has been used in the last decade to record diaphragmatic motion, the relation between diaphragmatic excursion and different inspired volumes (VT) has not been assessed by ultrasound. METHODS: Ten normal subjects were studied in the supine posture. Diaphragmatic excursion and VT were assessed simultaneously by M mode ultrasonography and respiratory airflow measurements at different inspired volumes. Ultrasound recordings of the movement of the right hemidiaphragm were carried out in the longitudinal plane subcostally. The transducer was held in a fixed position by a frame, built especially to eliminate any artefactual movement caused by outward motion of the anterior abdominal wall on inspiration. RESULTS: Mean (SD) maximal diaphragmatic excursion recorded was 6.0 (0.7) cm. Inspired volumes ranged from 15(5%) to 87(10%) of the subjects' inspiratory capacity. A linear relation between diaphragmatic excursion and VT was found in all subjects (r = 0.976-0.995). The regression line had a slope of 1.66 (0.24) cm/l. This slope had no correlation with either the height (r = 0.007) or weight (r = 0.143) of the subjects. In five subjects in whom diaphragmatic excursion could be recorded at volumes near total lung capacity, the relation between diaphragmatic excursion and VT became alinear at very high lung volumes. CONCLUSIONS: The relation between diaphragmatic excursion and VT was linear between 15(5%) and 87(10%) of inspiratory capacity. Ultrasonography of the diaphragm is a simple technique that could be applied in the clinical investigation of patients with suspected abnormalities of diaphragmatic movement.

Adult↗
PubMed1994

Diaphragmatic movement in hemiplegic patients measured by ultrasonography.

BACKGROUND: It is known that automatic breathing is controlled by centres in the lower brain stem, whereas volitional breathing is controlled by the cerebral cortical centres. In hemiplegia, lesions above the brain stem result in paralysis of limb muscles. This study was performed to determine whether the diaphragm might also be affected in patients with hemiplegia. METHODS: Studies were performed in six normal control subjects and in eight patients with complete hemiplegia caused by a lesion above the brain stem, all with no known chest disease. Full lung function tests were performed. Diaphragmatic excursion and inspired volume (VT) were measured simultaneously by M mode ultrasonography and respiratory airflow measurements. Recordings of diaphragmatic excursion were performed on each side separately during volitional and automatic breathing at a similar range of VT. RESULTS: Lung function tests lay within the normal range in all the control subjects. In the hemiplegic patients mean (SD) vital capacity was 79 (18)% and residual volume was 123(30)% of predicted. Total lung capacity and functional residual capacity were in the normal range. In the control subjects no significant difference in diaphragmatic excursion was found between volitional and automatic breathing for the same range of inspired volume. By contrast, there was a significant decrease in diaphragmatic excursion during volitional breathing compared with automatic breathing on the affected side in four of the eight hemiplegic patients. CONCLUSIONS: In four of eight hemiplegic patients reduced diaphragmatic movement was present on the paralysed side during volitional inspiration when compared with automatic inspiration. The hemidiaphragm may be involved on the affected side in patients with hemiplegia.

Aged↗
PubMed1993

Respiratory sensations in subjects who lack a ventilatory response to CO2.

An urge to breath is perceived during breath hold and hypercapnia (termed 'air hunger') and during heavy exercise (often termed 'shortness of breath'). To better understand the neural mechanisms responsible for these sensations we studied five patients (8-17 years old) with congenital central hypoventilation syndrome (CCHS) who lack ventilatory response to CO2. CCHS patients reported no respiratory discomfort during CO2 inhalation or during maximal breath hold which was of much longer duration than age-matched controls. However, all 3 CCHS patients who exercised heavily reported some sensations akin to shortness of breath (they increased breathing nearly as much as controls). Our results are consistent with two possibilities. First, the air hunger of hypercapnia and breath hold is caused by projection to the forebrain of respiratory chemoreceptor afferents which bypass the respiratory centers, while exercise shortness of breath is caused by direct projections of limb afferents or locomotory center activity. Second, air hunger and shortness of breath share the same origin--projection of increased brain stem respiratory center motor activity (corollary discharge) to the forebrain.

Adolescent↗
PubMed1993

Effects of inspiratory support upon breathing in humans during wakefulness and sleep.

We have compared the effects on breathing of inspiratory mechanical support during wakefulness and sleep in healthy subjects. Nine awake volunteers breathed through a nose mask connected to a machine supplying variable levels of inspiratory positive airway pressure (IPAP). Tidal volume (VT), breath duration (TTOT) and end-tidal PCO2 (PETCO2) were measured over 1 min steady state periods with IPAP set at a minimal level (approx. 2 cmH2O) and at approx. 10 cmH2O. This protocol was repeated in 6 of the subjects during non-REM sleep. When awake, "10 cmH2O IPAP" caused a significant increase in mean VT from 513 to 842 ml and a significant fall in PETCO2 from 39.7 to 32.7 mmHg. During sleep, "10 cmH2O IPAP" caused no significant changes in VT (388 to 390 ml) or PETCO2 (41.8 to 39.8 mmHg). In each state, "10 cmH2O IPAP" had no significant effect on TTOT. Three subjects repeated the protocol with diaphragmatic surface EMG recorded as an index of efferent inspiratory activity. "10 cmH2O IPAP" had no consistent effect on EMG when awake but caused a reduction in each subject during sleep. We conclude that during non-REM sleep, inspiratory mechanical support is associated with a compensatory decrease in efferent inspiratory activity to achieve a similar tidal volume with maintenance of arterial PCO2. When awake, a "wakefulness drive to breathe" may be associated with maintained inspiratory activity such that mechanical support results in an increased tidal volume despite a fall in arterial PCO2.

Adult↗
PubMed1993

Breathing patterns of monozygous twins during behavioural tasks.

To better understand behavioural and genetic influences upon breathing, the breathing patterns of 8 pairs of monozygous (MZ) twins were measured under 4 behavioural conditions; relaxed without standardisation; eyes closed; eyes open; and reading. Breathing was quantified by inspiratory and expiratory durations (TI, TE), tidal volume (VT) and derived variables. Airflow shape was normalised and quantified using 8 dimensions. Reading caused breathing to increase by > 500 ml/min compared to the other four conditions. Differences in breathing between combinations of two conditions were compared by testing whether the differences within an individual were smaller than the differences between random pairs of individuals from the same 16 subjects. For almost all respiratory variables, and whatever the behavioural condition, there were highly significant similarities within an individual (p < 0.00025 on 32/80 comparisons). Under each condition, the differences within MZ twin-pairs were compared to the differences within random-pairs from the same subject population. There were highly significant similarities within twin-pairs for the airflow shape across all conditions. However, TI, TE and VT failed to consistently show significant similarities within twin pairs. Hence, an individual's airflow shape appears to be a fundamental characteristic which is conserved when behavioural condition and level of ventilation changes. Further, MZ twins have similar airflow shapes--whatever the behavioural situation. Hence, behavioural influences upon airflow shape act upon monozygous twin pairs in similar ways, or such influences were negligible under the conditions of the present study.

Adolescent↗
PubMed1993

A method for the continuous measurement and display of pulmonary resistance in man.

1. We have validated a method for the continuous display and 'on-line' measurement of total pulmonary resistance in man, using a hybrid digital/analog computer. 2. The basic variables, which are measured by standard techniques, are flow rate of the mouth (V) and oesophageal pressure (Poes), and these are the only analog inputs necessary to the computer. 3. Resistance (RL,cont) is calculated continuously as: RL,cont = (Poes-V/C)/V where V is tidal volume and C is the dynamic compliance. RL,cont is continuously displayed as an analog signal on an oscilloscope. 4. Changes in resistance, measured by this method over a wide range of values in three subjects, showed an almost exact correlation with those measured by a standard method (Mead-Whittenberger).

Airway Resistance↗
PubMed1993

Reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in awake man.

This paper summarizes evidence for reflex genioglossus muscle activation by stimuli of negative airway pressure in normal, awake human subjects. Stimuli of negative airway pressure (range -5 to -35 cm H2O) caused activation of the genioglossus muscle. The larger values of negative pressure gave larger responses. Response latencies (median = 34 milliseconds) were much faster than the time for voluntary muscle activation (median = 184 milliseconds), suggesting that the responses were reflex in origin. The reflex nature of the responses was confirmed by studies with local anesthetics. The trigeminal, superior laryngeal and the glossopharyngeal nerves all mediated a component of the responses observed from the upper airway.

Air Pressure↗
PubMed1993

Within-breath modulation of left ventricular function during normal breathing and positive-pressure ventilation in man.

1. To investigate how intrathoracic pressure affects left ventricular function during normal breathing and positive-pressure ventilation, beat-by-beat measurements of left ventricular stroke volume (LVSV; pulsed Doppler ultrasound), heart rate and blood pressure were made in five normal subjects breathing actively and then undergoing passive positive-pressure ventilation. 2. To assess the within-breath effects of positive-pressure ventilation on left ventricular function in the clinical setting, further measurements were made in six patients sedated, paralysed and ventilated because of brain injuries, who had no disease of the heart or lungs. 3. In the normal subjects, there were minimal phasic variation in LVSV during positive-pressure ventilation with the subject passive. Heart rate and blood pressure also stayed relatively constant throughout the ventilator cycle. During active breathing at the same depth and rate, there were large phasic respiratory variations in LVSV, with the lowest values occurring during inspiration. 4. In the paralysed and unconscious patients, an increase in LVSV was associated with the increase in airway pressure which occurred during lung inflation; however, the phase lag between the rise in airway pressure and the rise in LVSV varied widely between patients. These changes occurred whether or not sinus arrhythmia was present. 5. Addition of 4.6 +/- 1 cmH2O of positive end-expiratory pressure (PEEP) did not increase the within-breath LVSV variations, but resulted in a mean depression of LVSV of 5.4% (paired t test, P = 0.035). 6. The smaller variations in LVSV during positive-pressure ventilation compared to normal breathing in the conscious subjects may reflect (a) the smaller magnitude of positive, compared to negative, pleural pressure excursions which accompany a given tidal volume, and (b) an asymmetry between the effects of positive and negative pleural pressure on the heart. 7. The prominent effects of positive-pressure ventilation on LVSV in unconscious patients, compared to the minimal effects seen in ventilated normal subjects, may result from reduced lung compliance and a degree of pulmonary vascular congestion in the patients which was undetectable clinically or radiologically.

Adolescent↗
PubMed1993

Regional cerebral blood flow during volitional expiration in man: a comparison with volitional inspiration.

1. Positron emission tomographic (PET) imaging of regional cerebral blood flow (rCBF), using a new 3-dimensional technique of data collection, was used to identify areas of neuronal activation associated with volitional inspiration and separately with volitional expiration in five normal male subjects. A comparison of the activated areas was also undertaken to isolate regions specific for one or other active task. 2. Scans were performed during intravenous infusion of H2(15)O under conditions of (a) volitional inspiration with passive expiration, (b) passive inspiration with volitional expiration and (c) passive inspiration with passive expiration. Four measurements in these three conditions were performed in each subject. Breathing pattern was well matched between conditions. 3. Regional increases in brain blood flow, due to increased neural activity associated with either active inspiration or active expiration, were derived using a pixel by pixel comparison of images obtained during the volitional and passive ventilation phases. Data were pooled from all runs in all subjects and were then processed to detect statistically significant (P < 0.05) increases in rCBF comparing active inspiration with passive inspiration and active expiration with passive expiration. 4. During active inspiration significant increases in rCBF were found bilaterally in the primary motor cortex dorsally just lateral to the vertex, in the supplementary motor area, in the right lateral pre-motor cortex and in the left ventrolateral thalamus. 5. In active expiration significant increases in rCBF were found in the right and left primary motor cortices dorsally just lateral to the vertex, the right and left primary motor cortices more ventrolaterally, the supplementary motor area, the right lateral pre-motor cortex, the ventrolateral thalamus bilaterally, and the cerebellum. 6. Using this modified and more sensitive PET technique, these findings essentially replicate those for volitional inspiration obtained in a previous study. For volitional expiration the areas activated are more extensive, but overlap with those involved in volitional inspiration. 7. The technique used has been successful in demonstrating the regions of the brain involved in the generation of volitional breathing, and probably in the volitional modulation of automatic breathing patterns such as would be required for the production of speech.

Abdominal Muscles↗