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Biomedical subjects

J A Innes

Publications and source records attributed to J A Innes.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effect of positive and negative step changes in intrathoracic pressure on left ventricular function in conscious man.

1. Breathing affects left ventricular stroke volume (LVSV) in normal subjects. The observed relationship may result from interaction between the effects of changing lung volume and intrathoracic pressure (IP). 2. To investigate the effect of IP on LVSV with minimal changes in lung volume, beat-by-beat LVSV (pulsed Doppler ultrasound) and systemic blood pressure (Finapres) were measured during obstructed inspiratory and expiratory efforts causing step changes in IP of +/- 15 cmH2O for 10 s, in seven subjects. Changes in mouth pressure (MP) during airway occlusion were used to indicate changes in IP. Group-averaged data for each second were compared to that in the second before the change in MP using Dunnet's multiple range test. 3. Step reductions in MP resulted in immediate and significant falls in LVSV (P < 0.05) and systolic blood pressure (P < 0.01) and increased heart rate, although this was not significant. These responses were transient, lasting only 3 s despite 10 s of reduced MP. 4. Step increases in MP caused biphasic cardiovascular responses. LVSV increased immediately, then fell significantly below control after 8 s (P < 0.01). Heart rate increased significantly between 5 and 9 s after the onset of the increase in MP (P < 0.05), suggesting activation of the baroreflexes by the accompanying progressive fall in systolic blood pressure. 5. The asymmetry in time course and magnitude between the responses to positive and negative pressure may reflect asymmetrical effects of MP on systemic venous return, right ventricular output, pulmonary venous return and left ventricular (LV) after-load, with the baroreceptors limiting changes in arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Central command influences cardiorespiratory response to dynamic exercise in humans with unilateral weakness.

1. Changes in ventilation and cardiovascular variables which occur during exercise may be partly due to 'radiation' of activity in central neurones innervating exercising muscles to the respiratory and cardiovascular control areas. To test this hypothesis, we compared ventilatory and cardiovascular responses to two levels of steady-state exercise with each leg separately, in subjects with painless unilateral leg weakness. We assumed that exercise with a weak leg would require more central neural drive than the same level of exercise with the normal leg. 2. Ventilation during exercise with the weak leg was greater than with the normal leg (P less than 0.02). This was a result of greater tidal volume (Vt; P less than 0.005). There was a greater increase in heart rate (P less than 0.005), and systolic (P = 0.001) and diastolic (P less than 0.02) blood pressures during exercise with the weak leg compared to exercise with the normal leg. The increases in stroke volume and cardiac output during exercise were not different with the two legs. 3. These results support the hypothesis that ventilation, blood pressure and heart rate are influenced by the central neural drive to exercise.

Adult↗
PubMed1992

Generation of cytolytic T cells in individuals infected by Mycobacterium tuberculosis and vaccinated with BCG.

BACKGROUND: Macrophage activation by cytokines provides only a partial explanation of antimycobacterial immunity in man. Because cytolytic T lymphocytes have been shown to contribute to immunity in animal models of intracellular infection, the generation of mycobacterial antigen specific cytotoxic T cells was examined in the peripheral blood of patients with tuberculosis. METHODS: Subjects comprised 36 patients with active tuberculosis (18 newly diagnosed) and 32 healthy volunteers, of whom 25 had had BCG vaccination and seven were Mantoux negative. The ability of purified protein derivative (PPD) stimulated peripheral blood lymphocytes to lyse autologous, mycobacterial antigen bearing macrophages was examined by using a chromium 51 release assay. RESULTS: PPD stimulated lymphocytes from normal, Mantoux positive, BCG vaccinated subjects produced high levels of PPD specific cytolysis, whereas lymphocytes from unvaccinated, uninfected subjects caused little or no cytolysis. The generation of cytolytic T lymphocytes by patients with tuberculosis was related to their clinical state. Those with cavitating pulmonary disease or lymph node tuberculosis generated PPD specific lymphocytes with cytotoxic ability similar to that of those from Mantoux positive control subjects, whereas lymphocytes from patients with non-cavitating pulmonary infiltrates showed poor antigen specific cytolysis. After seven days of stimulation with PPD in vitro, lymphoblasts contained both CD4+ and CD8+ cells. Mycobacterial antigen specific cytolysis was restricted to the CD4+ cell population and was blocked by monoclonal antibodies directed against major histocompatibility class II (MHC) antigens. CONCLUSION: CD4+ cytolytic T cells can lyse autologous macrophages presenting mycobacterial antigen and were found in patients with cavitating pulmonary tuberculosis or tuberculous lymphadenitis and in normal, Mantoux positive control subjects. The ability to generate these T cell responses seems to be a marker for response to mycobacteria and may contribute to tissue damage in tuberculosis. These responses do not provide protective immunity against Mycobacterium tuberculosis but may help in disease localisation.

BCG Vaccine↗
PubMed1991

Evidence for reflex upper airway dilator muscle activation by sudden negative airway pressure in man.

1. To determine if negative upper airway pressure causes reflex pharyngeal dilator muscle activation, we used intra-oral bipolar surface electrodes to record genioglossus electromyogram (EMG) activity in response to 500 ms duration pressure stimuli of 0, -2.5, -5, -15, -25 and -35 cm H2O (0-90% rise time less than 30 ms) in ten normal, conscious, supine subjects. 2. With the subjects relaxed at end-expiration, stimuli were applied in each of three conditions: (i) glottis open (GO), (ii) glottis closed (GC) and (iii) controls with the mouth and nose closed. 3. Six rectified and integrated EMG responses were bin averaged for each pressure in each experimental condition. Response latency was defined as the time when the EMG activity significantly increased above pre-stimulus levels. Response magnitude was quantified as the ratio of the EMG activity for 80 ms post-stimulus to 80 ms prestimulus; data from after the subject's voluntary reaction time (for tongue protrusion) were not analysed. 4. Negative airway pressure activated the genioglossus. The median latency of activation (34 ms) was much faster than the time for voluntary activation (184 ms) indicating a reflex response. 5. Significant activation, compared to 0 cmH2O controls and controls with mouth and nose closed, occurred with pressures of at least -5 cm H2O (GC) and -15 cm H2O (GO). At -25 and -35 cm H2O, responses with GO were significantly greater than with GC. 6. The magnitude ('strength') of the responses differed between subjects; these differences were repeatable. 7. We conclude that negative airway pressure causes reflex pharyngeal dilator muscle activation in man. Responses with GC suggest that upper airway receptors can mediate the response but larger responses with GO indicate a contribution from subglottal receptors.

Adult↗
PubMed1991

Afferent pathway(s) for pharyngeal dilator reflex to negative pressure in man: a study using upper airway anaesthesia.

1. To determine the afferent pathways mediating pharyngeal dilator muscle activation in response to negative airway pressure in man, we recorded genioglossus electromyogram (EMG) activity (via intra-oral bipolar surface electrodes) in response to 500 ms duration pressure stimuli of -15 and -25 cm H2O in normal, conscious, supine subjects relaxed at end-expiration; responses were compared before and after upper airway anaesthesia. 2. Six rectified and integrated EMG responses were bin averaged for pressure stimuli applied with the glottis open (GO) and closed (GC) and to the outside of the face only (controls). Response magnitude was quantified as the ratio of the EMG activity for an 80 ms post-stimulus period (before the subject's reaction time for tongue protrusion) to an 80 ms pre-stimulus period. 3. In eight subjects, upper airway anaesthesia reduced the EMG responses with GC to a level indistinguishable from controls. After anaesthesia, responses with GO remained higher than those with GC. 4. With GC, the mean EMG responses decreased by 43% after selective anaesthesia of the nasal mucosa (trigeminal nerves) in two subjects, 32% after selective anaesthesia of the laryngeal mucosa (superior laryngeal nerves) in six subjects and by 21% after selective anaesthesia of the oropharyngeal mucosa (glossopharyngeal and lingual nerves) in four subjects. 5. We conclude that upper airway afferents mediate pharyngeal dilator muscle activation in response to negative pressure with GC and that subglottal receptors caused the increased activation with GO. With GC, the trigeminal and superior laryngeal nerves mediate an important component of the responses with the glossopharyngeal nerves playing a less important role.

Adult↗
PubMed1991

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

Respiration during recovery from exercise: effects of trapping and release of femoral blood flow.

To investigate the contribution of vascular and metabolic stimuli to the sustained hyperpnea after exercise, the respiratory effects of obstructing and then releasing the femoral blood flow were recorded in 15 normal volunteers during recovery from steady-state cycle exercise (80 W). Obstruction was achieved using cuffs around the upper thighs, inflated for the first 2 min of recovery to a pressure of 200 mmHg. Cuff inflation significantly reduced ventilation during recovery compared with control (P less than 0.001); the subsequent release of pressure was accompanied by an increase in ventilation (averaging 3.2 l/min), which began on the first breath after release. This preceded a rise in end-tidal CO2 (maximum 8.3 Torr increase), which first became significant on the fourth breath after release and led to a further rise in ventilation. The first-breath increase in ventilation after cuff release persisted, although slightly attenuated (averaging 2.5 l/min), in additional experiments with inspired O2 fraction of 1.0. The pattern of ventilatory response was also similar when the experiments were performed with 5% CO2 in air as the inspirate. The immediate rise in ventilation on cuff release, together with the persistent response on 100% O2, suggests that the vascular changes resulting from cuff release exert an influence on ventilation independent of the effects of released metabolites on the known chemoreceptors. The persistence of the response on 5% CO2 indicates that CO2-sensitive lung afferents do not have a major role in these responses.

Adolescent↗
PubMed1989

Tuberculin testing: comparison of imotest with Heaf and Mantoux.

Immunisation against tuberculosis is still recommended for secondary school children in the UK. Only children who do not react to tuberculin tests are offered vaccination. We report the results of two studies, carried out to evaluate a new applicator of the disposable Imotest multiple puncture tuberculin test. The results demonstrate that Imotest is well tolerated and compares favourably with the Heaf and Mantoux tests. Imotest detected significantly more tuberculin responders than Heaf.

Child↗
PubMed1988

The effects of exercise and subject age on pulsed Doppler measurements of left ventricular ejection in normal man.

Pulsed Doppler measurements of ascending aortic blood velocity and acceleration were made in a group of normal subjects on exercise. The aims of the study were: (1) to document the normal response to exercise and its variability at various ages as a baseline for future studies in abnormal subjects, and (2) to investigate the accuracy and reproducibility of these noninvasive measurements. Doppler measurements were related to oxygen consumption in normal subjects aged between 22 and 69 years, during a submaximal 4 min incremental cycle exercise protocol. Computer-aided ensemble averaging of digital spectral data was used to reduce the effects of noise and respiratory variations in the signals. The mean relationship between cardiac output (Q) and oxygen consumption (Vo2) was Q = 5.75 Vo2 + 4.22 1 min-1, r = 0.84 in subjects aged under 45 years, compared to Q = 6.16 Vo2 + 3.87 1 min-1, r = 0.65 in older subjects; this difference was not significant. These values are similar to those previously described in invasive studies. There was a wide range of individual responses especially in the older subjects. These inter-subject differences probably reflect true physiological differences between subjects rather than methodological errors because they were consistent on repeated testing in the same individual, similar differences occurred in heart-rate responses between individuals where Doppler errors do not apply, and inter-subject variability of similar magnitude was found in comparable studies using invasive methods. Peak velocity (PV) rose from 73 +/- 10 cm s-1 at a Vo2 of 0.4 1 min-1 to 101 +/- 11 cm s-1 at a Vo2 of 1.21 min-1 in subjects aged under 45 years; corresponding values in the older subjects were significantly lower at 48 +/- 12 and 64 +/- 10 cm s-1 respectively. Maximum acceleration was also significantly higher at rest and on exercise in subjects under 45 years compared to older subjects. Despite these differences, stroke volume and cardiac output responses showed no significant age dependence, suggesting that differences in ejection velocity are due to increasing aortic cross-sectional area with age. The wide variety of individual responses found suggests an underlying variability in the arteriovenous oxygen difference on exercise between subjects.

Adult↗
PubMed1988

Ventilatory and circulatory responses at the onset of exercise in man following heart or heart-lung transplantation.

1. Ventilatory and cardiovascular responses to the onset of voluntary and electrically induced leg exercise were studied in six patients following heart transplantation and five following heart-lung transplantation; the results were compared between the patient groups and also with responses from a group of normal subjects. 2. Oxygen consumption, carbon dioxide production and ventilation and its components were measured over two 30 s periods prior to, and two 30 s periods following, the onset of exercise. Relative changes in stroke volume and cardiac output were derived from ensemble-averaged Doppler measurements of ascending aortic blood velocity over the same 30 s periods. 3. None of the groups of subjects showed any significant differences in responses to voluntary exercise compared to electrically induced exercise of similar work pattern and intensity. 4. Compared to normal controls, the transplanted subjects showed higher resting heart rates which did not increase at the onset of exercise; stroke volume increased, but less than in the normal subjects. The resulting cardiac output increases in the transplanted subjects were minimal compared to the normal subjects. 5. Ventilation and oxygen uptake increased immediately and with similar magnitude in all three groups. 6. These results show that in the same individual it is possible to have an appropriate ventilatory response to the onset of exercise in the presumed absence of a normal corticospinal input to the exercising muscles (electrically induced exercise) and afferent neural information from the lungs and heart, and in the absence of a normal circulatory response to exercise. The mechanisms underlying this ventilatory response remain undetermined.

Adult↗
PubMed1988

Protective effect of BCG vaccination in infant Asians: a case-control study.

BCG vaccination has been routinely offered to infant Asian children in Birmingham since 1965. We conducted a case-control study to assess the protective effect of this scheme. Altogether 108 Asian children aged under 13 years, born since 1965, received treatment for tuberculosis. For each case four controls were selected; they were matched to the case by month and year of birth, sex, and ethnic origin. Cases and controls were all born in Birmingham. Of the cases, 62 out of 108 (57%) had received BCG, and of the controls, 336 out of 432 (78%) had received BCG. The estimated protective efficacy of vaccination was 64% (95% confidence limits, 43% and 77%). Routine BCG vaccination in infant Asians confers useful protection against the development of tuberculosis in childhood.

Adolescent↗
PubMed1987

Validation of beat by beat pulsed Doppler measurements of ascending aortic blood velocity in man.

The volume, velocity, and acceleration of ascending aortic blood were measured in man using a pulsed Doppler ultrasound instrument, with online spectral analysis and offline computer processing of velocity data. This system was firstly validated in a test rig capable of generating pulsatile flow of talc particles in water at physiological velocities and accelerations in a model aorta. Doppler measurements correlated well (r greater than or equal to 0.90) with simultaneous electromagnetic measurements of stroke volume, peak ejection velocity, and maximum acceleration in this rig. In vivo validation was performed firstly by comparing simultaneous Doppler and thermodilution cardiac output (Q) measurements; this yielded the following regression equation: Doppler Q = 0.90 X thermodilution Q + 0.03 litre.min-1, r = 0.92; n = 38. Beat by beat measurements were then validated against simultaneous invasive aortic blood velocity measurements made using a Mills electromagnetic cathetertip probe. When paced single beats of different size were compared within subjects the correlation coefficients between Doppler and electromagnetic measurements averaged 0.89 for stroke volume, 0.91 for peak ejection velocity, and 0.79 for maximum acceleration in five subjects. The absolute values for velocity and acceleration from the Doppler system differed significantly from the absolute values given by the electromagnetic system and this difference was not consistent between subjects. It is concluded that the Doppler system can non-invasively record relative changes in left ventricular ejection in man.

Aorta↗
PubMed1987

The early circulatory and ventilatory response to voluntary and electrically induced exercise in man.

1. The ventilatory and circulatory responses to electrically induced leg exercise (EEL) were studied in seven normal subjects and compared with the responses to performing the same exercise voluntarily (EV). 2. EEL was produced by surface electrode stimulation of the quadriceps and hamstring muscle groups. This produced a push-relax pattern of exercise against a spring load and was free of any pain or discomfort. EV, at the same level, was achieved by subjects copying a display of timing and force information on a storage oscilloscope. 3. Cardiac output was estimated using validated Doppler ultrasound measurements of the velocity in the ascending aorta, combined with an estimate of aortic cross-sectional area using M-mode echocardiography. 4. Data from EV and EEL exercise runs were matched, within subjects, for the increase in oxygen consumption during the first 30 s of exercise; there were no significant differences between the resting states prior to either form of exercise. 5. The first ten beats of exercise were used to study the circulatory on-transient. The cardiac output responses to both EV and EEL were similar; however, in EV alone there was an initial significant drop in stroke volume and a slightly greater rise in heart rate. 6. The first five breaths of the response were used to study the ventilatory on-transient, and by measuring cardiac output, stroke volume and heart rate throughout each breath, the relationship between circulatory and ventilatory variables could be assessed. Ventilation showed a significantly greater rise at the onset of exercise during EV than during EEL; PET,CO2 (end-tidal CO2 pressure) showed small but significant falls for both EV and EEL. 7. The circulatory changes on a breath-by-breath basis are similar for EV and EEL although the ventilatory changes differ. In both EV and EEL the average increase in ventilation at the onset of exercise is proportionally greater than the average increases in cardiac output. Individual exercise runs show no particular relationship between circulatory and ventilatory change. 8. The results provide no support in man during mild leg exercise for a 'cardiodynamic' drive to breathing.

Adult↗