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Biomedical subjects

A Guz

Publications and source records attributed to A Guz.

At least 145 records · Page 8Linked to original sources

Respiratory modulation of left ventricular stroke volume in man measured using pulsed Doppler ultrasound.

1. Beat-by-beat changes in left ventricular stroke volume (l.v.s.v.) with breathing were recorded in four normal subjects using pulsed Doppler ultrasound. The l.v.s.v. fell during inspiration and rose during expiration; these changes were exaggerated at high tidal volumes. 2. Respiratory changes in l.v.s.v. persisted when respiratory rate was increased to 25 breaths/min despite an associated reduction in the degree of sinus arrhythmia. 3. During relaxed breath-holding, respiratory variations in l.v.s.v. ceased immediately, and on resumption of breathing a significant fall in l.v.s.v. occurred with the first inspiratory effort. 4. Inspiratory efforts against an occluded mouthpiece were accompanied by significant variations in l.v.s.v., although the magnitude of these changes was smaller than during unoccluded breathing with similar pleural pressure changes. 5. A resistive inspiratory load increased the respiratory variations in l.v.s.v. in the three subjects studied. 6. In three patients with implanted dual-chamber pacemakers set to constant heart rates, breathing was associated with larger variations in l.v.s.v. 7. In two patients who had undergone pericardectomy, the magnitude of respiratory changes in l.v.s.v. was less than in the normal subjects. 8. We conclude that inspiration directly lowers l.v.s.v. in man by a direct mechanism which is largely independent of lung volume changes, is dependent on changes in pleural pressure, and persists in the absence of sinus arrhythmia. All these results, particularly those in pericardectomy patients, are compatible with previous animal work on the anatomical and functional interdependence of right and left ventricles during breathing.

Adult↗

Breathlessness.

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Humans↗

Aerosol anesthesia increases hypercapnic ventilation and breathlessness in laryngectomized humans.

The effect of local anesthetic aerosol inhalation on the ventilatory response and the sensation of breathlessness to CO2 rebreathing was studied in seven healthy male subjects with permanent tracheal stomas after laryngectomy for carcinoma. Inhalation of bupivacaine aerosol sufficient to abolish the cough reflex to mechanical probing below the carina increased the ventilatory response to CO2 in six of seven subjects compared with saline control. This was achieved by an increase in both respiratory frequency (f) and tidal volume (VT) in four subjects, f in one subject, and VT in one subject. All subjects reported that they were more breathless on rebreathing after bupivacaine aerosol. The six subjects who recorded breathlessness with a visual analog scale (VAS) indicated its onset at a lower minute ventilation (VE) and gave higher VAS scores for equivalent levels of VE after threshold. We conclude that the enhanced CO2 sensitivity and breathlessness on rebreathing after airway anesthesia results from altered lower airway receptor discharge.

Aged↗

Effects of cigarette smoking and drugs on respiratory tract proteases and antiproteases.

Increased pulmonary proteolytic (elastolytic) activity is thought to be the primary cause of emphysema and may also play a rôle in the pathology of bronchitis. These diseases are common amongst tobacco smokers. Serum-derived alpha 1-proteinase inhibitor (alpha 1PI) and locally produced protease inhibitors normally protect the pulmonary epithelium from proteolytic attack, but tobacco smoke can inactivate these antiproteases by oxidative and non-oxidative mechanisms. Bronchoalveolar lavage fluid (BALF) samples lung surface components and most studies show that there is elevated elastolytic activity in smokers' BALF. Whether antiproteolytic capacity is reduced in these samples remains debatable. A selective lavage technique is described which independently samples central and peripheral epithelium from the same subject. Analysis demonstrates a protease-antiprotease imbalance which can differ in central and peripheral lavage and which could be significant in the development of obstructive airways disease. Therapeutic approaches include augmenting antiprotease potential using genetically engineered, oxidant-resistant alpha 1PI or synthetic peptide inhibitors.

Epithelium↗

The measurement of breathlessness induced in normal subjects: individual differences.

Normal subjects show wide variability in their sensory scaling of breathlessness for equivalent degrees of ventilatory stimulation and behave "characteristically' irrespective of stimulus type. Observed differences are not explained by physical characteristics, ventilatory sensitivity or pattern of breathing although there is a weak association with the degree of physical fitness. Differences are seen when scaling is performed with reference to both rigidly defined extremes of breathlessness (visual analogue scaling) and a subject's own relative changes in the intensity of this sensation (magnitude estimation). These findings may explain the common observation, in patients with respiratory disease, of dyspnoea out of proportion to the pathophysiological state.

Adult↗

Respiratory and cardiovascular effects of central and peripheral intravenous injections of capsaicin in man: evidence for pulmonary chemosensitivity.

The respiratory and cardiovascular effects of capsaicin injection into the superior vena cava and an arm vein were studied in three normal subjects. No changes were seen in tidal volume, inspiratory time or expiratory time after capsaicin injection. Instantaneous heart rate, systolic blood pressure and diastolic blood pressure remained unchanged. Central and peripheral intravenous injections of capsaicin but not control solution above a threshold of 0.5 micrograms/kg produced dose-dependent sensations sequentially in the chest, face, rectum and extremities. The chest sensation, a 'raw, burning' feeling, occurred 3-4 s after central capsaicin injection. No subject reported feeling breathless. In one subject the maximum tolerable dose of capsaicin (4 micrograms/kg) produced paroxysmal coughing 3.9 s after a central injection. In two of the subjects capsaicin injection was repeated after inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter 4.8 micron), sufficient to block the cough reflex to a 5% citric acid aerosol. Prior inhalation of local anaesthetic aerosol abolished the chest sensation after capsaicin injection; the other sensations were unaffected. This study demonstrates that stimulation of receptors accessible from the pulmonary vascular bed does not evoke the pulmonary chemoreflex in conscious man but can produce coughing. It provides evidence for the existence of a nociceptive system of nerve endings in the lung parenchyma that can be blocked by inhaled local anaesthetic aerosol.

Bupivacaine↗

Acid-stable low molecular mass proteinase inhibitors in human lung lavage.

An acid-stable, low molecular mass proteinase inhibitor, bronchial mucus proteinase inhibitor (BMPI), has been isolated from sputum and partially characterised. A single band with a modal molecular mass of 18 700 was observed following SDS-polyacrylamide gel electrophoresis. BMPI inhibited human leukocyte elastase, cathepsin G, trypsin and chymotrypsin, but not porcine pancreatic elastase. Although BMPI had a molecular mass close to the similarly isolated inhibitor of Girard et al. (Girard, F., Tournier, J.M., Polu, J.M. & Sadoul, P. (1980), Bull. Eur. Physiopathol. Respir. 16 (Suppl.) 237-245), and although it showed immunological cross reactivity to the low molecular mass inhibitor of Kramps et al. (Kramps, J.A., Franken, C., Meyer, C.J.L.M. & Dijkman, J.H. (1981) J. Histochem. Cytochem. 29, 712-719), it was found to have an amino-acid profile different to any previously described inhibitor. BMPI was detectable in bronchoalveolar lavage fluid collected from healthy and diseased human lungs. The median molar ratio of BMPI/alpha 1-proteinase inhibitor (alpha 1 PI) observed in these lavage samples was 0.7, which is generally higher than those derived from the data of other authors. This suggests that BMPI is a different protein to those previously described, although its exact relationship to other low molecular mass proteinase inhibitors remains to be determined.

Amino Acids↗

The effect of airway anaesthesia on the control of breathing and the sensation of breathlessness in man.

The effect on ventilation of airway anaesthesia, produced by the inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter = 4.77 micron), was studied in 12 normal subjects. The dose and distribution of the aerosol were determined from lung scans after the addition to bupivacaine of 99mTc. Bupivacaine labelled in this way was deposited primarily in the central airways. The effectiveness and duration of airway anaesthesia were assessed by the absence of the cough reflex to the inhalation of three breaths of a 5% citric acid aerosol. Airway anaesthesia always lasted more than 20 min. Resting ventilation was measured, by respiratory inductance plethysmography, before and after inhalation of saline and bupivacaine aerosols. The ventilatory response to maximal incremental exercise and, separately, to CO2 inhalation was studied after the inhalation of saline and bupivacaine aerosols. Breathlessness was quantified by using a visual analogue scale (VAS) during a study and by questioning on its completion. At rest, airway anaesthesia had no effect on mean tidal volume (VT), inspiratory time (Ti), expiratory time (Te) or end-tidal PCO2, although the variability of tidal volume was increased. On exercise, slower deeper breathing was produced and breathlessness was reduced. The ventilatory response to CO2 was increased. The results suggest that stretch receptors in the airways modulate the pattern of breathing in normal man when ventilation is stimulated by exercise; their activation may also be involved in the genesis of the associated breathlessness. A hypothesis in terms of a differential airway/alveolar receptor block, is proposed to explain the exaggerated ventilatory response to CO2.

Adult↗

Arterial oxygen desaturation during treadmill and bicycle exercise in patients with chronic obstructive airways disease.

Nine men with severe chronic obstructive airways disease (COAD), known to desaturate on exercise, performed a 6 min self-paced walk on a treadmill, followed by a bicycle exercise with workloads adjusted to mimic the oxygen consumption achieved on the treadmill. During both exercises, ventilation, oxygen consumption, carbon dioxide production, PaO2, PaCO2, pH and arterial lactate were measured and subjective breathlessness recorded. A reasonable match of oxygen consumption between the two exercises was achieved. In all subjects PaO2 fell to a lower level during treadmill compared with bicycle exercise. Ventilation, carbon dioxide production and arterial lactate were higher during bicycle exercise. Subjective breathlessness was greater during bicycle exercise, in proportion to the higher ventilation on the bicycle. The greater anaerobiosis occurring on the bicycle led to acidosis and an increased ventilation, minimizing the exercise fall in PaO2. Bicycle testing may seriously underestimate exercise desaturation occurring during level walking in patients with severe COAD.

Aged↗

The measurement of breathlessness induced in normal subjects: validity of two scaling techniques.

The intensity of breathlessness induced by ventilatory stimulation resulting from hypercapnia, hypoxia or exercise has been quantified in normals by using the two different sensory scaling techniques of linear visual analogue scaling and ratio magnitude estimation. In naive individuals both techniques show good face validity. When related to ventilation, quantification of breathlessness is moderately reproducible with both methods, even when subjects are kept in ignorance of the pattern of ventilatory stimulation. There is a small within- and large between-subject variability with both scaling techniques; possible factors responsible are discussed. The reproducibility of visual analogue scaling when related to ventilation is independent of the nature of the ventilatory stimulus and is maintained over intervals as long as 1 week when memory for the score given is unlikely to be an important factor. The difficulties of interpreting subjective estimates of perceived breathlessness are discussed, together with the relative merits of the two scaling techniques.

Adult↗

Extracellular elastolytic activity in human lung lavage: a comparative study between smokers and non-smokers.

Unrestrained proteolysis in the lung is believed to initiate emphysema, a disease common among tobacco smokers. However, few studies have found extracellular protease activity in human lung lavage. In this investigation, elastase and serine protease activities were measured in bronchoalveolar lavage supernatants (BAL) from patients undergoing routine investigations. Significantly more elastolytic activity (against insoluble [3H]-elastin) was recovered in the lavage of smokers than that of non-smokers. However, no significant difference was found when the levels of serine proteolytic activity (against N-succinyl-L-trialanyl-p-nitroanilide) were compared. The elastolytic component of the protease activity rose from 5% in non-smokers' BAL to over 30% in that of smokers, suggesting that elastase activity is selectively enhanced by smoking. In lavages from most smokers, 80% or more of the elastase activity was serine-dependent, whereas lavages from non-smokers contained variable proportions of serine elastase. Both alpha 1-proteinase inhibitor (alpha 1-PI) and a low molecular weight antiprotease, bronchial mucus proteinase inhibitor (BMPI) were detectable in the lavage samples, the latter contributing up to 76% of the total antiprotease quantified in the lavage. Functional antiprotease was detected in 85% of the lavages. Since there were no differences in either antiprotease levels or functional inhibitory capacities between lavages from smokers and controls, it is concluded that the imbalance in the protease/antiprotease profile of the smokers' lung results from an enhancement of proteases, specifically of elastolytic activity, rather than a reduction in inhibitory capacity.

Adolescent↗

Breathlessness during different forms of ventilatory stimulation: a study of mechanisms in normal subjects and respiratory patients.

This study investigates the mechanisms underlying the perception of breathlessness induced by hypoxia and hypercapnia in both naive normal subjects and patients with respiratory mechanical problems. In normal subjects separately receiving both oscillating hypercapnic and hypoxic ventilatory stimulation, equivalent peak stimulus intensities in end-tidal gas were associated with a 'damped' ventilatory response when the frequency of stimulation was increased. A concomitant fall in peak breathlessness levels on a visual analogue scale was recorded in each case. In normal subjects and patients, the voluntary copying of a ventilatory pattern recorded during oscillating hypercapnic stimulation was associated with a marked diminution or complete absence of breathlessness despite equivalent levels of peak ventilations achieved. Voluntary copying of hypercapnic stimulated ventilation was not associated with any demonstrable change in the distribution of muscle movements between the chest wall and abdomen. These results suggest that the intensity of breathlessness depends on the level of effective reflex stimulation of the respiratory-related neurones in the medulla. They cannot be explained solely in terms of perception of afferent neural information arising from either chemoreceptors or respiratory mechanoreceptors.

Abdomen↗

A self paced treadmill walking test for breathless patients.

A treadmill exercise test is described that retains the advantages of self paced walking but allows the measurement of cardiorespiratory variables. A horizontal treadmill was modified to allow patients to control their own speed. During exercise continuous measurements of speed, distance, heart rate, arterial oxygen saturation, and stride length were made and subjective assessments of breathlessness were recorded on a visual analogue scale. Ten men with severe chronic obstructive lung disease performed a 12 minute corridor walk and a self paced 12 minute treadmill walk on the same day and repeat treadmill walks on different days. Six of them performed three walks or more. Six patients had ventilatory measurements during treadmill exercise. There was no significant difference (p greater than 0.1) in the distance covered during corridor and treadmill walks, and distances on the treadmill were repeatable after the first walk. Use of a mouthpiece significantly reduced the distance covered on the treadmill. The self paced treadmill walk is a simple repeatable test and has advantages over both a corridor walking test and standard progressive tests for assessment of breathless patients.

Aged↗

Respiratory impairment induced by smoking in children in secondary schools.

A longitudinal study was carried out from 1975 to 1979 in a cohort of 405 secondary school children. At yearly intervals they underwent a series of tests of pulmonary function designed to monitor lung development; some of these tests are relatively sensitive indicators of early abnormalities. A self administered questionnaire provided details of smoking habits and respiratory symptoms. The prevalence of smoking increased with age; most of those smoking at 16 had already been smoking, at least experimentally, at 13. Taking up smoking was clearly associated with the early onset of cough, production of phlegm, and shortness of breath on exertion. After two years of smoking more than a few cigarettes a day the children who smoked appeared considerably less healthy than their non-smoking peers and showed some evidence of early obstruction of the airways.

Adolescent↗

Is the voluntary control of exercise in man necessary for the ventilatory response?

The ventilatory response to electrically induced exercise (EEL) was studied in eighteen normal subjects and compared with the response to performing the same exercise voluntarily (EV). EEL was produced by surface electrode stimulation of the quadriceps and hamstring muscles so as to cause a pushing movement at 1 HZ against a spring load; this produced no pain or discomfort. Matching of EV to EEL was achieved by subjects copying a tension signal recorded during EEL and displayed on a storage oscilloscope. There were no differences between the resting states measured before either form of exercise. The ventilatory response (change in ventilation as a ratio of the change in CO2 elimination) was similar in the two types of exercise. The increases in ventilation and CO2 elimination were greater with EEL. Small but significant increases in the gas exchange ratio and serum lactate were found for EEL but not for EV, suggesting an increase in anaerobic metabolism in EEL. End-tidal PCO2 showed little change in either form of exercise. In some runs end-tidal PCO2 rose, but insufficiently to account for the ventilatory response as judged by the response to inhaled CO2. In two subjects arterial blood samples showed small and inconsistent changes in both Pa,CO2 and PaO2 for EV and EEL. pH and base excess changes also were consistent with more anaerobiosis with EEL compared to EV. The first ten breaths of exercise were used to study the on transient. In EV, expiratory duration shortened and ventilation increased significantly on the first breath but CO2 elimination did not increase until the second breath; in EEL, these variables did not change significantly until the second breath. For the remainder of the on transient the pattern of the ventilatory response was similar for EV and EEL. By the end of the on transient both EV and EEL had reached approximately 80% of their final steady-state values. These results suggest that a normal ventilatory response can occur in the absence of a drive to exercise from the cortex.

Adult↗