Biomedical subjects

D K McKenzie

Publications and source records attributed to D K McKenzie.

At least 19 recordsLinked to original sources

PubMed2001

Changes in respiratory sensations induced by lobeline after human bilateral lung transplantation.

1. The sensations evoked by the injection of lobeline into the right antecubital vein were studied in 8 subjects after bilateral lung transplantation and 10 control subjects. In control subjects, two distinct sensations were experienced. There was an early noxious sensation (onset approximately 10 s) followed by a late sensation of breathlessness (onset approximately 26 s) associated with involuntary hyperventilation. The early sensation was accompanied by respiratory and cardiovascular changes. 2. In contrast to control subjects, the early respiratory events and the noxious sensations evoked by injections of lobeline (18-60 microg kg(-1)) did not occur in subjects with recent bilateral lung transplantation. This suggests that the early respiratory sensations are mediated by the discharge of receptors in the lungs. 3. The late hyperventilation and the accompanying sensation of breathlessness occurred in both transplant and control subjects and are therefore likely to be mediated by receptors elsewhere in the body, presumably systemic arterial chemoreceptors stimulated by lobeline. 4. In control subjects, but not transplant subjects, there was a consistent decrease in mean arterial pressure associated with the lobeline injection. This suggests that pulmonary afferents mediate the hypotension. 5. For transplant subjects studied more than a year after transplantation, there was some evidence that the noxious respiratory sensations evoked by lobeline had returned. This suggests that some functional reinnervation of pulmonary afferents may occur.

Adult↗

PubMed2001

Discharge frequencies of single motor units in human diaphragm and parasternal muscles in lying and standing.

Single motor unit discharge was measured directly in diaphragm and parasternal intercostal muscles to determine whether neural drive to human inspiratory muscles changes between lying and standing. The final discharge frequency of diaphragmatic motor units increased slightly, by 1 Hz (12%; P < 0.01), when subjects were standing [182 units, median 9.1 Hz (interquartile range 7.6-11.3 Hz)] compared with lying supine [159 units, 8.1 Hz (6.6-10.3 Hz)]. However, this increase with standing occurred in only two of six subjects, in one of whom tidal volume increased significantly during standing. Parasternal intercostal motor unit final discharge frequencies did not differ between standing [116 units, 8.0 Hz (6.6-9.6 Hz)] and lying [124 units, 8.4 Hz (7.0-10.3 Hz)]. The discharge frequencies at the onset of inspiration did not differ between lying and standing for either muscle. A larger proportion of motor units in both inspiratory muscles had postinspiratory or tonic expiratory activity for lying compared with standing (15 vs. 4%; P < 0.05). We conclude that there is no major difference in the phasic inspiratory drive to the diaphragm with the change in posture.

Diaphragm↗

PubMed2000

Estimation of diaphragm length in patients with severe chronic obstructive pulmonary disease.

In patients with advanced chronic obstructive pulmonary disease (COPD) diaphragm function may be compromised because of reduced muscle fibre length. Diaphragm length (L(Di)) can be estimated from measurements of transverse diameter of the rib cage (D(Rc)) and the length of the zone of apposition (L(Zapp)) in healthy subjects, but this method has not been validated in patients with COPD. Postero-anterior chest radiographs were obtained at total lung capacity (TLC), functional residual capacity (FRC) and residual volume (RV) in nine male patients with severe COPD (mean [S.D.]; FEV(1), 23 [6] %pred.; FRC, 199 [15] %pred.). Radiographs taken at TLC were used to identify the lateral costal insertions of the diaphragm (L(Zapp) assumed to approach zero at TLC). L(Di) was measured directly and also estimated from measurements of L(Zapp) and D(Rc) using a prediction equation derived from healthy subjects. The estimation of L(Di) was highly accurate with an intraclass correlation coefficient of 0.93 and 95% CI of approximately +/-8% of the true value. L(Di) decreased from 426 (64) mm at RV to 305 (31) mm at TLC. As there were only small and variable changes in D(Rc) across the lung volume range, most of the L(Di) changes occurred in the zone of apposition. Additional studies showed that measurements of L(Di) from PA and lateral radiographs performed at different lung volumes were tightly correlated. These results suggest that non-invasive measurements of L(Zapp) in the coronal plane (e.g. using ultrasonography) and D(Rc) (e.g. using magnetometers) can be used to provide an accurate estimate of L(Di) in COPD patients.

Aged↗

PubMed2000

A prospective study of atropine premedication in flexible bronchoscopy.

AIM: This study aimed to assess the effect of atropine premedication prior to flexible bronchoscopy. The rationale for using atropine is that it will dry secretions and allow a better view of the bronchial tree. There is also the theoretical benefit of protection against vasovagal episodes and bronchospasm. METHODS: Twenty patients were randomised in a double-blind manner to receive either 500 mcg of atropine intramuscularly or 1 mL of 0.9% saline intramuscularly 30 minutes prior to bronchoscopy. Both groups received a standard dose of intramuscular pethidine. Variables studied included a pre-procedure electrocardiograph, a rhythm strip during the procedure, serial measurements of blood pressure, continuous pulse oximetry, and spirometry pre- and post-bronchoscopy. Subjective measures recorded were a secretion score, rated 0-3 by the bronchoscopist using a four point visual analogue scale. A patient questionnaire was designed to establish the presence or absence of symptoms, including those related to atropine. RESULTS: There were no significant differences recorded in the duration of procedure, percentage fall in FEV1, secretion scores, or other physiological measures. The only significant difference between the two groups was dry mouth in the atropine group (p<0.001). There was a fall in forced vital capacity from baseline which was significant in the saline group (p<0.005), and not the atropine group, but it was not significant when compared between groups. A beta2 adrenergic agonist would, however, be more appropriate to prevent such a fall in spirometry. CONCLUSIONS: These results fail to demonstrate a benefit of intramuscular atropine as premedication for fibreoptic bronchoscopy.

Aged↗

PubMed1999

Discharge properties and recruitment of human diaphragmatic motor units during voluntary inspiratory tasks.

1. The behaviour of inspiratory motoneurones is poorly understood in humans and even for limb muscles there are few studies of motoneurone behaviour under concentric conditions. The current study assessed the discharge properties of the human phrenic motoneurones during a range of non-isometric voluntary contractions. 2. We recorded activity from 60 motor units in the costal diaphragm of four subjects using an intramuscular electrode while subjects performed a set of voluntary inspiratory contractions. These included a range of inspiratory efforts above and below the usual tidal range: breaths of different sizes (5-40 % vital capacity, VC) at a constant inspiratory flow (5 % VC s-1) and breaths of a constant size (20 % VC) at different inspiratory flows (2.5-20 % VC s-1). 3. For all the voluntary tasks, motor units were recruited throughout inspiration. For the various tasks, half-way through inspiration, 61-87 % of the sampled motor units had been recruited. 4. When the inspiratory task was deliberately altered, most single motor units began their discharge at a particular volume even when the rate of contraction had altered. 5. The initial firing frequency (median, 6.5 Hz) was consistent for tasks with a constant flow regardless of the size of the breath. However, for breaths of a constant size the initial firing frequencies increased as the inspiratory flow increased (range across tasks, 4.8-9.3 Hz). The 'final' firing frequency at the end of inspiration increased significantly above the initial frequency for each task (by 0.8-5.2 Hz) and was higher for those tasks with higher final lung volumes and higher inspiratory flows (range across tasks, 7.8-11.0 Hz). 6. There was no correlation within a task between the time of recruitment and the initial or final firing frequency for each motor unit. However, for each inspiratory task, initial and final firing frequencies were positively correlated. 7. Because the discharge of three to four units could be recorded simultaneously in a range of tasks, a quantitative 'shuffle' index was developed to describe changes in their recruitment order. Recruitment order was invariant in the task with the slowest inspiratory flow, but varied slightly, but significantly, in tasks with higher inspiratory flows. 8. The discharge rates of single motor units were compared for targeted voluntary breaths and non-targeted involuntary breaths which were matched for size. There were no significant differences in the initial or final firing frequencies, but recruitment order was not always the same in the two types of breath.

Adult↗

PubMed1999

Task failure, breathing discomfort and CO2 accumulation without fatigue during inspiratory resistive loading in humans.

Task failure during inspiratory resistive loading has been attributed to inspiratory muscle fatigue. Six subjects breathed at their own rate and duty cycle through an inspiratory resistive load to a target mouth pressure of 80% maximal inspiratory pressure (MIP) until task failure, when breathing discomfort (measured with a modified Borg scale) was maximal. Six protocols were used to vary ventilatory parameters and hence the rate of rise, of end-tidal CO2. MIP did not decline during resistive loading in any protocol, but there were significant increases in end-tidal CO2 (ranging from 1.0 to 3.9). Time to task failure increased in protocols that enabled subjects to reduce the rate of CO2 accumulation. Differences in endurance times between subjects were related to their sense of breathing discomfort with rising CO2 measured in separate rebreathing studies. Task failure was due to breathing discomfort associated with CO2 accumulation and sensations related to the generation of large inspiratory pressures, rather than inspiratory muscle fatigue.

Adult↗

PubMed1999

Effects of increased ventilatory drive on motor unit firing rates in human inspiratory muscles.

This study was designed to determine whether increased neural drive increases firing rates of inspiratory motoneurons uniformly in humans. The discharge of single motor units in the diaphragm, parasternal intercostal and scalene muscles was recorded with monopolar electrodes. Ventilation was increased threefold with an external dead space. The discharge of 516 motor units was sampled in four subjects. All but 4 units increased their discharge rate during inspiration with only 46 discharging tonically during expiration. With increased dead space, discharge frequencies of diaphragmatic motor units increased from 11.0 +/- 2.7 to 17.7 +/- 3.3 Hz (mean +/- SD; p < 0.001). However, firing rates increased for parasternal intercostals from 10.0 +/- 1.6 to only 11.9 +/- 1.9 Hz (p < 0.001), and for scalenes from 8.7 +/- 1.8 to only 9.5 +/- 1.2 Hz (p < 0.05). Proportionate increases in rib cage and abdominal expansion accompanied the increased ventilation with added dead space. These results suggest that previously reported predominant increase in firing rates of diaphragmatic motor units in patients with chronic airflow limitation reflects the normal response of respiratory motor output to increased neural drive. The motoneuron pools of the parasternal intercostals and scalenes may show more prominent recruitment than frequency modulation.

Action Potentials↗

PubMed1998

Twitch interpolation of the elbow flexor muscles at high forces.

We investigated factors affecting maximal voluntary torque and the assessment of the level of voluntary drive in the elbow flexor muscles. First, the effective compliance of the system was tested by using single, paired, and trains of four stimuli to measure voluntary activation. At high voluntary torques the responses to all these stimuli were identical, suggesting that single stimuli are adequate for estimating voluntary drive. Second, the contribution of torque from synergist elbow flexor muscles was assessed. In attempted maximal voluntary contractions (MVCs), the voluntary activation of brachioradialis (median 91.5%, range 68.9-100%) was lower than for biceps brachii (median 99.1%, range 78.5-100%; P < 0.01). This suggests extra torque may be generated by brachioradialis during elbow flexion, beyond the torque where biceps brachii is maximally activated. Finally, lengthening of the elbow flexors occurred during MVCs, due to slight shoulder movements. This would allow force to increase independently of an increase in voluntary drive.

Adult↗

PubMed1998

Human respiratory muscles: sensations, reflexes and fatiguability.

1. Given the importance of the ventilatory 'pump' muscles, it would not be surprising if they were endowed with both sensory and motor specializations. The present review focuses on some unexpected properties of the respiratory muscle system in human subjects. 2. Although changes in blood gas tension were long held not to influence sensation directly, studies in subjects who are completely paralysed show that increases in arterial CO2 levels elicit strong sensations of respiratory discomfort. 3. Stretch reflexes in human limb muscles contain a monosynaptic spinal excitation and a long-latency excitation. However, inspiratory muscles show an initial inhibition when tested with brief airway occlusions during inspiration. This inhibition does not depend critically on input from pulmonary or upper airway receptors. 4. Human inspiratory muscles (including the diaphragm) have been considered to fatigue during inspiratory resistive loading. However, recent studies using phrenic nerve stimulation to test the force produced by the diaphragm show that carbon dioxide retention (hypoventilation) and voluntary cessation of loading occur before the muscles become overtly fatigued.

Carbon Dioxide↗

PubMed1997

Contraction of the human diaphragm during rapid postural adjustments.

1. The response of the diaphragm to the postural perturbation produced by rapid flexion of the shoulder to a visual stimulus was evaluated in standing subjects. Gastric, oesophageal and transdiaphragmatic pressures were measured together with intramuscular and oesophageal recordings of electromyographic activity (EMG) in the diaphragm. To assess the mechanics of contraction of the diaphragm, dynamic changes in the length of the diaphragm were measured with ultrasonography. 2. With rapid flexion of the shoulder in response to a visual stimulus, EMG activity in the costal and crural diaphragm occurred about 20 ms prior to the onset of deltoid EMG. This anticipatory contraction occurred irrespective of the phase of respiration in which arm movement began. The onset of diaphragm EMG coincided with that of transversus abdominis. 3. Gastric and transdiaphragmatic pressures increased in association with the rapid arm flexion by 13.8 +/- 1.9 (mean +/- S.E.M.) and 13.5 +/- 1.8 cmH2O, respectively. The increases occurred 49 +/- 4 ms after the onset of diaphragm EMG, but preceded the onset of movement of the limb by 63 +/- 7 ms. 4. Ultrasonographic measurements revealed that the costal diaphragm shortened and then lengthened progressively during the increase in transdiaphragmatic pressure. 5. This study provides definitive evidence that the human diaphragm is involved in the control of postural stability during sudden voluntary movement of the limbs.

Adult↗

PubMed1997

Task failure with lack of diaphragm fatigue during inspiratory resistive loading in human subjects.

Task failure during inspiratory resistive loading is thought to be accompanied by substantial peripheral fatigue of the inspiratory muscles. Six healthy subjects performed eight resistive breathing trials with loads of 35, 50, 75 and 90% of maximal inspiratory pressure (MIP) with and without supplemental oxygen. MIP measured before, after, and at every minute during the trial increased slightly during the trials, even when corrected for lung volume (e.g., for 24 trials breathing air, 12.5% increase, P < 0.05). In some trials, task failure occurred before 20 min (end point of trial), and in these trials there was an increase in end-tidal PCO2 (P < 0.01), despite the absence of peripheral muscle fatigue. In four subjects (6 trials with task failure), there was no decline in twitch amplitude with bilateral phrenic stimulation or in voluntary activation of the diaphragm, even though end-tidal PCO2 rose by 1.6 +/- 0.9%. These results suggest that hypoventilation, CO2 retention, and ultimate task failure during resistive breathing are not simply dependent on impaired force-generating capacity of the diaphragm or impaired voluntary activation of the diaphragm.

Adult↗

PubMed1997

Pulmonary afferents are not necessary for the reflex inhibition of human inspiratory muscles produced by airway occlusion.

In contrast to limb muscles, the usual response of human inspiratory muscles to sudden loading consists of an initial marked reduction of electromyographic activity (EMG) followed by a subsequent increase in EMG. To determine definitively whether pulmonary receptors are necessary for this short-latency reflex inhibition produced by airway occlusion, we studied five subjects with complete pulmonary denervation due to bilateral transplantation of the lungs and five matched control subjects. Subjects with pulmonary denervation were studied between 10 and 50 days after transplantation (median 21 days). Brief airway occlusion during inspiration (i.e., loading; duration 250 ms) produced short-latency reduction in EMG in the inspiratory muscles of all subjects with acute pulmonary denervation (scalenes and parasternal intercostal muscles; mean onset of inhibition 27 and 29 ms, respectively). The ongoing EMG was reduced by an average of 50% in scalenes and 36% in parasternal intercostal muscles. The size and the magnitude of the initial response did not differ significantly from those in control subjects. After the occlusion (i.e., unloading), activity of the inspiratory muscles was transiently reduced in control subjects and patients after bilateral lung transplantation. Given that the initial responses to airway loading and unloading were preserved after bilateral lung transplantation, we conclude that these reflex responses are not critically dependent on the discharge of intrapulmonary receptors. The results support the view that the short-latency inspiratory responses to loading and unloading can be mediated by inspiratory muscle afferents. They suggest a functionally different organization of the reflex pathways for inspiratory compared with limb muscles.

Adolescent↗

PubMed1997

Neural drive to the diaphragm in patients with severe COPD.

Patients with severe chronic obstructive pulmonary disease (COPD) have a greater neural drive to the parasternal intercostal and scalene muscles and greater inspiratory expansion of the rib cage than do healthy individuals. However, such patients also have a reduced outward displacement or a paradoxical inward displacement of the ventral abdominal wall during inspiration. This has led to the suggestion that they may have less use of the diaphragm, possibly secondary to chronic muscle fatigue. To assess the effect of COPD on the neural drive to the diaphragm, we inserted needle electrodes into the costal part of the right hemidiaphragm in eight patients with severe disease (mean [+/- SD] FEV1: 0.82 [+/- 0.27] L) and six control subjects of similar age, and measured the discharge frequencies of single motor units during resting breathing. A total of 115 diaphragmatic motor units were recorded in the control subjects and 122 in the patients. All motor units discharged rhythmically in phase with inspiration. However, whereas 95% of the units in the control subjects had a peak discharge frequency between 7 and 14 Hz, 79% of the units in the COPD patients had a peak discharge frequency greater than 15 Hz. As a result, the discharge frequency of all units averaged 10.5 [+/- 2.4] Hz in the control subjects, but 17.9 [+/- 4.3] Hz in the patients (p < 0.001). These observations indicate that patients with severe COPD have an increased neural drive not only to the rib cage inspiratory muscles, but also to the diaphragm. Consequently, the reduced inspiratory expansion of the abdomen in severe COPD results from mechanical factors alone.

Aged↗

PubMed1996

Reduced voluntary drive to the human diaphragm at low lung volumes.

Maximal inspiratory and transdiaphragmatic pressures vary with lung volume but the possibility that some of this variability reflects variable voluntary drive to the diaphragm has not been investigated systematically. We assessed the influence of lung volume on the ability to activate the diaphragm with voluntary effort during maximal Mueller manoeuvres. Voluntary activation of the diaphragm was assessed using twitch interpolation with bilateral phrenic nerve stimulation in 6 subjects. Each performed 10 maximal efforts at lung volumes around functional residual capacity (FRC) and additional efforts at volumes above and below FRC. Voluntary activation of the diaphragm was higher at lung volumes above FRC (> 60% TLC; activation 98.3 +/- 2.6%) than at lung volumes around FRC (45-60% TLC; activation 95.5 +/- 3.5%) and below FRC (< 45% TLC; activation 83.3 +/- 15.8%; p < 0.05). Submaximal diaphragm activation at low lung volumes may reflect differences in the length-tension relationships of the various inspiratory muscles and/or reflex inhibition of phrenic motoneurones at low lung volumes.

Adult↗

PubMed1996

Impaired reflex responses to airway occlusion in the inspiratory muscles of asthmatic subjects.

BACKGROUND: Asthmatic subjects have an impaired capacity to activate the diaphragm during attempted maximal inspiratory efforts. Limb muscles require reflex facilitation to achieve maximal force. The reflex responses of inspiratory muscles to airway occlusion in asthmatic subjects were measured and compared with those in non-asthmatic control subjects. METHODS: Nine healthy asthmatic subjects breathed at a constant inspiratory flow through a low resistance valve. Random inspirations were transiently occluded for 250 ms. Surface electromyographic activity (EMG) was recorded over the scalene muscles, parasternal intercostal muscles, and the lateral chest wall overlying the diaphragm. The asthmatic subjects were studied with and without bronchoconstriction. Responses were compared with data from a matched group of 12 control subjects. RESULTS: Compared with the reflex responses to airway occlusion in control subjects, the duration of the initial short latency inhibition of inspiratory muscles was prolonged by 50% in asthmatic subjects and the size of the subsequent excitation was reduced by 30%. Bronchoconstriction reduced the time to the peak of the excitatory response in asthmatic subjects, although the values remained longer than in the control subjects. CONCLUSIONS: This study reveals impaired reflex excitation of inspiratory motoneurones in asthmatic subjects which could contribute to the reduced ability of these subjects to drive the diaphragm during maximal volitional efforts.

Adolescent↗

PubMed1996

Discharge frequencies of parasternal intercostal and scalene motor units during breathing in normal and COPD subjects.

To determine whether patients with chronic obstructive pulmonary disease (COPD) contract the inspiratory muscles of the rib cage more strongly than do healthy subjects, we recorded the discharge frequencies of single motor units in the scalene and second parasternal intercostal muscles of seven patients with stable COPD (FEV1 = 33 +/- 13% predicted, mean +/- SD) and seven control subjects. Recordings were made with insulated monopolar electrodes during resting breathing, and single motor-unit discharges were identified with a customized method based on "template" matching. A total of 211 motor units were recorded in the control subjects and 260 in the patients. The inspiratory discharge frequencies were greater in the COPD patients than in the control subjects for both the parasternal (13.4 versus 10.1 Hz, p < 0.05) and scalene (11.4 versus 8.5 Hz, p < 0.02) muscles. Recording sites at which no motor units were recruited were more common in the control subjects than in the patients (p < 0.001). The sternomastoid muscle was silent in both subject groups. Therefore, effective central neural drive is increased to both the scalene and parasternal intercostal muscles but not to the sternomastoid muscle in patients with COPD.

Action Potentials↗

PubMed1995

Role of airway receptors in the reflex responses of human inspiratory muscles to airway occlusion.

1. This study was designed to investigate the role of airway receptors in the responses of a range of inspiratory muscles to airway occlusion. The occlusion had a rapid onset (< 10 ms), lasted 250 ms and produced only a slight impediment to inspiration. 2. Based on analysis of single trials and averaged rectified electromyographic responses (EMG) in six subjects, there was a major inhibition (IR) with an onset at 34 +/- 2 ms and a trough at 65 +/- 2 ms, and an excitation (ER) with a peak at 105 +/- 2 ms. These two responses are reflex given that voluntary reaction times to a tap on the chest wall occurred at latencies longer than the peak of ER. 3. The responses to airway occlusion did not appear in limb muscles which contracted phasically with inspiration. 4. Anaesthesia of the surface receptors of the upper airway did not attenuate the responses to occlusion. Because this procedure does not eliminate the inputs from muscle and deep laryngeal pressure receptors, two subjects were tested when intubated with a cuffed endotracheal tube so that the occlusion was delivered only to structures below the level of the trachea. Responses to airway occlusion were preserved when all upper airway receptors were 'bypassed'. 5. Responses to airway occlusion also remained after prolonged inhalation of nebulized lidocaine (lignocaine) sufficient to block the cough reflex. 6. The receptors mediating the responses to airway occlusion are therefore likely to reside in inspiratory muscles acting on the chest wall. If so, the short-latency inhibition contrasts with the excitatory stretch reflex responses observed in limb muscles.

Adaptation, Physiological↗

PubMed1995

Reliability of measurements of muscle strength and voluntary activation using twitch interpolation.

We investigated the reproducibility of measurements of maximal voluntary torque and maximal voluntary activation using twitch interpolation. On 5 days, each of 5 subjects performed 10 maximal voluntary isometric contractions of their elbow flexors. Single supramaximal stimuli were delivered over biceps brachii at the measured peak torque during each effort, and in the relaxed muscle 5 s later. A voluntary activation score was calculated from the size of twitches evoked by the stimuli (resolution < 0.15 Nm). Although all subjects were able to drive the stimulated elbow flexor muscles maximally in some trials, they did not do so in 75% of all contractions. Maximal voluntary torques did not vary significantly within a subject between sessions. There were consistent differences in the level of maximal voluntary activation between subjects (P < 0.01), but no differences in voluntary activation within an individual across days in 4 of 5 subjects. Failure to drive the stimulated elbow flexor muscles maximally was not associated with inadvertent co-contraction of the antagonist muscles.

Adult↗