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Biomedical subjects

A Guz

Publications and source records attributed to A Guz.

At least 91 records · Page 5Linked to original sources

Cardiac output, oxygen consumption and arteriovenous oxygen difference following a sudden rise in exercise level in humans.

1. To investigate the relative contributions of increases in cardiac output and arteriovenous oxygen difference to the increase in oxygen consumption during exercise, the ventilatory and cardiovascular responses to a sudden transition from unloaded cycling to 70 or 80 W were measured in six normal healthy subjects. 2. Oxygen consumption (VO2) was measured breath-by-breath and corrected for changes in lung gas stores. Cardiac output (Q) was measured beat-by-beat using pulsed Doppler ultrasound, and blood pressure was measured beat-by-beat using a non-invasive finger cuff (Finapres). All data were calculated off-line, second-by-second. 3. Arteriovenous oxygen difference (A-VO2) was calculated from Q and VO2 using the Fick Principle. Left ventricular afterload was calculated by dividing Q by mean blood pressure. 4. The data for Q and VO2 were closely fitted by single exponential curves (mean r2 0.84 and 0.90 respectively; r is the correlation coefficient). These curves yielded mean time constants for the increases in Q and VO2 of 28 and 55 s respectively following the increase in exercise level. In each individual subject, the time course of adjustment of Q was faster than that of VO2. There was a mean lag of 15 s from the start of the new exercise level before the derived A-V O2 began to increase; the mean time constant for A-V O2 was 57 s. 5. If A-V O2 had remained constant, the observed rise in Q alone would have resulted in an average of 87% of the increase in VO2 which was observed after 5 s. If Q had remained constant, the observed increase in A-V O2 would have led to only 8% of the actual increase in VO2 after 5 s. 6. Mean and systolic blood pressure rose and afterload fell immediately after the onset of the increased workload. The time constants of the systolic blood pressure and afterload responses to exercise varied widely and ranged from 37 to 81 and 10 to 26 s respectively (n = 4). 7. We conclude that Q is responsible for most of the early increase in VO2 following a sudden increase in exercise workload. Blood pressure responses to exercise are slower than Q and VO2 responses, probably due to the rapid decrease in afterload. 8. The dominant contribution of Q to adaptation to changing workload may be physiologically important particularly in heart disease, where decreased ability to increase cardiac output may limit the capacity to cope with changing metabolic needs during everyday activities.

Adaptation, Physiological↗

Regional cerebral blood flow during volitional breathing in man.

1. Positron emission tomographic imaging of brain blood flow was used to identify areas of motor activation associated with volitional inspiration in six normal male subjects. 2. Scans were performed using intravenous infusion of H2(15)O during voluntary targeted breathing and positive pressure passive ventilation at the same level. 3. Regional increases in brain blood flow, due to active inspiration, were derived using a pixel by pixel comparison of images obtained during the voluntary and passive ventilation phases. 4. Pooling data from all subjects revealed statistically significant increases in blood flow bilaterally in the primary motor cortex (left, 5.4%; right, 4.3%), in the right pre-motor cortex (7.6%), in the supplementary motor area (SMA; 3.1%) and in the cerebellum (4.9%). 5. The site of increased neural activation in the motor cortex, associated with volitional inspiration, is consistent with an area which when stimulated, either directly during neurosurgery or transcranially with a magnetic stimulus, results in activation of the diaphragm. 6. The presence of additional sites of neural activation in the pre-motor cortex and SMA appears analogous to the results of studies on voluntary limb movement. The site of the increase in the SMA was posterior to that previously reported for arm movements. These areas are believed to have a role 'upstream' of the motor cortex in the planning and organization of movement. 7. This technique provides a means of studying the volitional motor control of respiratory related tasks in man.

Adult↗

Motor cortical representation of the diaphragm in man.

1. Transcranial magnetic stimulation was performed using a figure-of-eight-shaped coil over the right motor cortex with the aim of identifying those areas involved with activation of the diaphragm. 2. The response of the right and left hemi-diaphragms was recorded using surface electrodes in either the 7th or 8th intercostal spaces 3 cm lateral to the anterior costal margin on either side. 3. The compound muscle action potentials recorded over the left diaphragm in response to transcranial magnetic stimulation were maximal when the centre of the figure-of-eight coil was placed approximately 3 cm to the right of the mid-line and 2-3 cm anterior to the auricular plane. 4. The amplitude of the response recorded from the diaphragm depended upon the angulation of the figure-of-eight coil and hence the direction of the stimulating current. 5. The response of the inspiratory muscles to magnetic stimulation of one side of the brain was predominantly contralateral but a small response was seen on the ipsilateral side. Ultrasonic techniques confirmed that the diaphragm was responding contralaterally and not ipsilaterally.

Action Potentials↗

The language of breathlessness. Use of verbal descriptors by patients with cardiopulmonary disease.

The main objective of the present study was to test the hypothesis that patients with cardiopulmonary disease can reliably identify different sensory qualities of their experience of breathlessness. A secondary aim was to examine whether there was any relationship between such specific descriptors of the sensation of breathlessness and a patient's clinical diagnosis. A randomly ordered list of 45 descriptors of breathing discomfort related to exertion was administered on two occasions to 208 patients with cardiopulmonary disease; patients identified the descriptors that applied to their own experience. A total of 169 patients were considered reliable in that their responses were repeatable between questionnaires; there was evidence that an individual's reliability could be assessed by asking repeat questions within a questionnaire. With these patients, individual descriptors generated different degrees of yes and no response and were answered with a variable consistency, suggesting that some questions may be more useful than others in discriminating between the quality of patients' sensations. Overall, patients with obstructive disorders (asthma and chronic obstructive airways disease [COAD]) answered yes more often than those with restrictive or cardiac conditions, possibly reflecting differences in severity of disease. A cluster analysis separated the descriptors into 12 groups which appeared to describe different aspects of breathing discomfort. Relative to their response to other clusters, COAD patients were more inclined to identify distress, asthma patients to indicate wheeziness, restrictive patients to report rapid breathing, and the cardiac group to describe a need to sign. A second cluster analysis separated patients into 12 groups based on responses for the descriptor clusters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Capillary blood cell velocity is reduced in fever without hypotension.

Capillary blood cell velocity was measured in a group of normotensive febrile patients as a basis for further study into the microvascular physiology of febrile hypotensive patients with sepsis. Television videomicroscopy was used to record the capillary blood cell movement in the finger nailfold. Analysis of all moving gaps in the red cell column seen during a minimum of 2 minutes was done by the frame-by-frame technique and mean blood cell velocity derived. Core (external auditory meatus) and skin (finger) temperature were also measured. Subjects (n = 6) were sex and skin temperature matched to controls. Although the mean skin temperature of subjects [28.73 degrees C, SD = 0.28] was not significantly different to controls [30.63 degrees C, SD = 3.11; p less than 0.05] the mean velocity was significantly reduced in the febrile subject group [0.28 mm/sec, SD = 0.17] as compared with controls [0.56 mm/sec, SD = 0.22; p less than 0.05]. It is likely therefore that these skin vessels vasoconstrict as part of the integrated response to reduce heat loss.

Adolescent↗

An assay for the assessment of lipocortin 1 levels in human lung lavage fluid.

The physiological function of the lipocortins, proteins which are thought to be glucocorticoid-regulated, is unclear. An improved assay for lipocortins might help to elucidate their role. A rapid and specific sandwich enzyme-linked immunosorbent assay (ELISA) for lipocortin 1 with a working range of 1-2000 ng/ml and an interrun coefficient of variation of less than 10% is described and used in this pilot study to quantify human lipocortin 1 for the first time in acellular bronchoalveolar lavage fluid (BALF), and in media conditioned by BAL cells, from control patients and those with pulmonary sarcoidosis. Using this assay a statistically significant relationship, not previously observed in man, has been demonstrated between concentrations of lipocortin 1/ml of BALF and serum cortisol levels (n = 10, rs = 0.6939, P less than 0.05). Although lipocortin 1 levels in acellular BALF were the same in control and sarcoid patients, significantly more lipocortin 1 was released from sarcoid BAL cells in culture (median 21.6, range 8.1-45.4 ng lipocortin/10(6) cells/h in culture) than from control cells (2.5, 1.5-7.6 ng lipocortin/10(6) cells/h in culture). The possible clinical significance of these data is discussed, but remains to be established.

Annexins↗

The persistence of a respiratory 'personality' into stage IV sleep in man.

The characteristic pattern of breathing for an individual when awake at rest may be due to forebrain influences upon breathing. To examine this hypothesis we have studied the breathing pattern in 18 healthy subjects during relaxed wakefulness (W) and during Stage 4 sleep (S4), when forebrain influences upon breathing are absent or minimal. Inspiratory and expiratory times, respiratory frequency, tidal volume, and ventilation were quantified noninvasively by respiratory inductance plethysmography. The stability of respiratory variables between W and S4 sleep was tested within individuals. The results show that (i) individuals breathe differently from each other when awake and when in S4 sleep; the range between individuals during sleep being as large as it is when awake; (ii) differences in breathing pattern between two S4 periods within an individual are relatively small; (iii) the characteristic breathing pattern of an individual when awake tends to be maintained in S4 sleep. This persistence of a respiratory 'personality' into S4 sleep probably indicates that there are individual differences in respiratory rhythm generation in the absence of any forebrain influences upon breathing.

Adult↗

Effect on breathing of raising end-expiratory lung volume in sleeping laryngectomized man.

In animals, tonic vagal activity from lung receptors provides a means by which changes in end-expiratory lung volume can influence respiratory timing. We wished to examine whether increasing the end-expiratory lung volume within the tidal volume range had a similar effect in man. In order to minimize behavioral influences on breathing, the study was performed in subjects during deep non-rapid eye movement sleep. Five laryngectomized subjects were chosen for the study since their permanent tracheal stomata allow simple, airtight connection to respiratory apparatus and avoided problems with glottic closure. During EEG-documented sleep, end-expiratory volume was increased by up to 350 ml with the addition of expiratory threshold loads of 1 to 10 cm H2O. End-expiratory volume increased linearly with expiratory pressure. Inspiratory and expiratory times (TI and TE) were not affected by increases in end-expiratory volume. Tidal volume (VT) was decreased such that end-inspiratory volume remained unchanged. The decrease in VT may result from a reduction in inspiratory muscle efficiency at a higher lung volume. The results of the study provide no evidence that tonic vagal afferent information from the lungs is important in controlling respiratory rhythm within the tidal volume range in man when behavioral control of breathing is minimized.

Adult↗

Putative cerebral cortical involvement in the ventilatory response to inhaled CO2 in conscious man.

1. The response of the diaphragm to both transcranial magnetic stimulation and electrical phrenic nerve stimulation was studied in thirteen normal subjects under conditions of either a 'reflex' drive to ventilation with inhaled CO2 or during volitional ventilation of similar magnitude. 2. The induced compound action potential in the diaphragm was recorded using an oesophageal electrode, and in some cases transdiaphragmatic pressure was recorded using oesophageal and gastric balloon catheters. 3. The response of the diaphragm to transcranial magnetic stimulation was invariably facilitated with volitional inspiration; there was either minimal or no response at functional residual capacity. 4. Facilitation with inspiration was also seen during a 'reflex' drive to ventilation with inhaled CO2 in the presumed absence of any volitional contribution to ventilation. A similar degree of facilitation was seen with voluntary ventilation of similar magnitude and pattern. 5. If the facilitation is predominantly a cortical phenomenon, then these results imply that there is a behavioural component in the previously supposed purely 'reflex' drive to ventilation with inhaled CO2. We also discuss the interpretation of these results if some of the facilitation occurs at the phrenic motoneurone.

Action Potentials↗

The effects of hypoxia and hypercapnia on perceived breathlessness during exercise in humans.

1. The sensation of breathlessness increases when ventilation is reflexly stimulated but it is not clear whether different stimuli have specific effects in the genesis of this sensation. 2. Our aim was to compare subjective assessments of the intensity of breathlessness at the same levels of ventilation induced by different combinations of reflex ventilatory stimuli. 3. Against a background of progressive exercise (maximum workload 170 W) in 'blinded' normal naive subjects, normoxic hypercapnia (maximum end-tidal CO2, PET, CO2, 56 mmHg) or isocapnic hypoxia (minimum O2 saturation 88%) was induced to achieve levels of ventilation (maximum 60 l min-1) 'matched' with those resulting from a higher intensity of exercise alone. Subjective breathlessness was rated with a visual analogue scale. 4. For a given ventilation, compared with exercise alone, breathlessness scores were similar during hypercapnia and were lower during hypoxia. 5. These results do not support the idea that during exercise, hypercapnia or hypoxia has a specific role in the genesis of the sensation of breathlessness. 6. The findings are consistent with the hypothesis that the degree of reflex ventilatory activation, however achieved, is an important determinant of the intensity of perceived breathlessness in healthy humans.

Adult↗

Type II pneumocytes in mixed cell culture of human lung: a light and electron microscopic study.

Alveolar Type II epithelial cells dedifferentiate rapidly in vitro. Studies with animal tissue suggest that cell-cell and extracellular matrix-cell interactions are important in the retention of Type II cell morphology in vitro. Thus, in this study with human tissue, alveolar Type II cells, alveolar macrophages, and spindle cells were prepared from the same sample of lung (obtained following lobectomy for cancer, n = 3), cocultured on glass cover slips or tissue culture plastic, and studied by light microscopy with scanning (SEM) and transmission (TEM) electron microscopy for 8 days. The primary cell isolates contained approximately 45% Type II cells; the remainder were macrophages or unidentifiable cells. Clusters, made up of a single layer of cuboidal Type II cells around a central core of connective tissue (largely collagen and some elastic tissue), formed above a monolayer of spindle cells. The Type II cells were morphologically similar to those seen in vivo. The cells were still cuboidal at 8 days but had lost their lamellar bodies, which were released into the medium via the apical surface. The clusters increased in size with time (area, microns 2: day 1, 29(5-143) x 10(2); day 8, 63(10-311) x 10(2); mean(range); p less than 0.02) without changing in number per culture, suggesting Type II cell proliferation. This may have been due to factors produced by the other cells and adherence to the extracellular matrix (ECM); (free collagen fibers, present in the original preparation, spindle cells, and/or Type II cells could be responsible for presence of ECM). We propose this as a useful model for the study of human Type II epithelial cells in vitro.

Cell Differentiation↗

Detection of lipocortin 1 in human lung lavage fluid: lipocortin degradation as a possible proteolytic mechanism in the control of inflammatory mediators and inflammation.

Lipocortins are structurally related, glucocorticoid-inducible proteins that inhibit phospholipase A2 (PLA2), thereby reducing the liberation of arachidonic acid from phospholipids and so limiting the synthesis of eicosanoid inflammatory mediators. This study is the first demonstration of one lipocortin, lipocortin 1 (Lc 1; 37 kDa), in human lung lavage supernatants. In lavage fluid from healthy volunteers, a higher percentage (greater than 70%) of the detected Lc 1 was in its native form, compared to that from patients with abnormal lungs. In patients' lavage fluids, Lc 1 was more likely to be partially degraded (34 kDa). In abnormal bronchoalveolar lavage fluid (BALF), the more polymorphonuclear neutrophils (PMN)/lavage, the lower the proportion of Lc 1 in the native (37 kDa) form (n = 7 pairs, rs = -0.8214, p less than 0.05). Furthermore, when BALF cells were cultured and the harvested conditioned media incubated with pure human recombinant Lc 1, degradation of the 37 kDa form increased with the percentage of PMN (n = 10 pairs, s = -0.7200 after 1 hr; n = 6 pairs, rs = -0.9241 after 6 hr). These results suggest that factors released from the PMN are responsible for Lc 1 degradation in man. When recombinant human Lc 1 was incubated with human neutrophil elastase, the enzyme degraded Lc 1 in a dose-dependent way, suggesting that neutrophil elastase may be one such factor. Since PMNs are ubiquitous at sites of inflammation, it is possible that Lc 1 degradation is a permissive mechanism, which ensures that sufficient inflammation occurs to destroy the provocative stimulus. However, it is equally possible that, in some circumstances, the mechanism may be pathological and that the inactivation of Lc 1 leads to chronic, uncontrolled inflammation.

Adult↗

Individuality of breathing patterns in adults assessed over time.

Sixteen healthy adult subjects underwent two studies separated by 4-5 years to test whether their resting pattern of breathing was reproducible over time. From breath-by-breath analysis of airflow, measured with a pneumotachometer, the pattern of breathing was quantified in terms of individual respiratory variables; inspiratory time (TI), expiratory time (TE), total breath duration (TTOT), tidal volume (VT), VT/TI, TI/TTOT, and by taking TI, TE and VT all together (TRIAD). Also, the shape of the entire airflow profile was quantified by harmonic analysis (ASTER). A statistical analysis was designed to compare differences between the 1st and the 2nd recording within individuals with those differences observed between random pairs of recordings from the two studies in the same 16 individuals. It was found that all variables were significantly more similar within-individuals than between-individuals; this is best demonstrated when considering the ASTER and/or the TRIAD. It was concluded that the individuality of breathing pattern is maintained over a long period despite changes in smoking habit, weight, mild respiratory diseases, and other changes which occurred between the two studies in our subjects.

Adult↗

The breathing patterns of identical twins.

The resting breathing patterns of healthy adult identical twins were compared to see if there was any possible genetic component in the determination of this pattern. From breath-by-breath analysis of airflow, measured with a pneumotachometer (9 pairs of twins), the pattern of breathing was quantified in terms of individual respiratory variables; inspiratory time (TI), expiratory time (TE), total breath duration (TTOT), VT/TI, TI/TTOT, and by taking TI, TE and VT all together (TRIAD). Also, the airflow shape was quantified by harmonic analysis (ASTER). A second study was performed under more strictly defined conditions of rest and where the respiratory variables were estimated with respiratory inductance plethysmography to eliminate the possible effect of a facemask (5 pairs of twins). In each study, for each variable, the differences within twin-pairs were compared to the differences within random-pairs from the same subject population. In both studies, there were highly significant similarities within twin-pairs in the pattern of breathing, being best demonstrated when the entire 'shape' of the pneumotachogram (ASTER) or the spirogram (TRIAD) was considered.

Adolescent↗

Studies on the circulation in normotensive febrile patients.

Normotensive febrile patients were studied in a constant-temperature room during stable fever, They were restudied later while afebrile and after heating the trunk. Finger and forearm blood flow were measured by venous occlusion plethysmography. The ability of cutaneous vessels to constrict on dependence of the limb was measured by laser Doppler flowmetry. The volume, velocity and acceleration of the blood in the ascending aorta were determined using pulsed Doppler ultrasound with a probe in the supra-sternal notch; measurements of systolic time intervals were made. While febrile, patients had a tachycardia and shortened systolic ejection times; cardiac output and total peripheral resistance were unchanged on average as compared to when afebrile. There was no evidence of any change in left ventricular contractility during fever from measurements of the peak velocity, maximum acceleration of blood or from the systolic time intervals. As compared to when heated, febrile patients had a skin blood flow that was relatively reduced for their skin temperature and had preservation of postural vasoconstriction.

Adult↗

Synchronization of motor unit firing during different respiratory and postural tasks in human sternocleidomastoid muscle.

1. Motor unit firing has been studied in human sternocleidomastoid muscle. 2. Two needle electrodes were inserted into the muscle and the activity of pairs of motor units recorded during (a) reflex hypercapnic obstructed breathing, (b) eucapnic voluntary copying of (a) against the same inspiratory resistance and (c) voluntary copying of (a) without any resistance, accompanied by isometric neck rotation. 3. Cross-correlation histograms of the firing of unit pairs showed a clear central peak, indicative of synchronization. The mean duration of the peak during voluntary breathing was 25 ms (range 9-40 ms). There was no difference in duration of synchronization during the different tasks. 4. For the duration of the synchronization peak, the mean strength of synchronization expressed as the number of concomitant discharges of the two units as a proportion of the total number of discharges was 0.026 (range 0.011-0.058) for reflex hypercapnic obstructed breathing. For the same unit pairs the strength of synchronization for isometric neck rotation was the same as that during reflex hypercapnic breathing but for voluntary obstructed breathing it was, on average, threefold greater. 5. In three out of twenty-two motor units studied, 'discharge' occurred with an interval of less than 10 ms ('doublet' firing) at the onset of each inspiration during both types of obstructed breathing; this was rarely observed during neck rotation. 6. The results are interpreted in terms of different synaptic drives to the motor units during the three different tasks.

Adult↗

Cardiopulmonary response to dynamic exercise after heart and combined heart-lung transplantation.

The exercise capacity and cardiopulmonary response to progressive dynamic exercise of eight healthy recipients of heart-lung transplants were compared with those of matched recipients of orthotopic cardiac transplants and normal controls. In both transplant groups the maximum workloads were lower than that in the normal group. The transplant recipients had higher pre-exercise heart rates and lower maximum heart rates than the normal controls. Ventilation during submaximal exercise was similar in the heart transplant group and the controls. The heart-lung group had an increased ventilatory response associated with lower end tidal carbon dioxide concentrations. Exercise capacity after combined heart-lung transplantation is similar to that after cardiac transplantation. Transplant recipients have an abnormal heart rate response during exercise related to cardiac denervation. The altered ventilatory response in heart-lung recipients may be the result of pulmonary denervation.

Adolescent↗