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Papers by David McKenzie

Journal of Applied Physiology, 2001

Respiratory Physiology Neurobiology, Oct 16, 2003

In animals, high-intensity unilateral stimulation of the phrenic nerve results in short-latency i... more In animals, high-intensity unilateral stimulation of the phrenic nerve results in short-latency inhibition of phrenic and intercostal nerve activity bilaterally. This study provides the first demonstration in human subjects of a short-latency inhibitory response in the contralateral scalene, parasternal intercostal and diaphragm muscles to single stimuli delivered at cervical level to the phrenic nerve. Electromyographic (EMG) responses were recorded with intramuscular and surface electrodes. An inhibitory response with an onset latency of approximately 35 ms followed by a long-latency excitatory response at approximately 100 ms were observed in the three inspiratory muscles. The inhibition was evident in single trials, averaged EMG, histograms of the discharge of single motor units, and even when the phrenic nerve stimulus intensity was relatively low. Thus, the inhibition may be mediated by large-diameter muscle afferents. The latency of this potent inhibitory response to contralateral phrenic nerve stimulation is too long to be mediated via a simple spinal circuit and may involve a brainstem projection.

American Journal of Respiratory and Critical Care Medicine, Dec 20, 2012

Panic attacks are common in chronic obstructive pulmonary disease (COPD), and the prevalence of p... more Panic attacks are common in chronic obstructive pulmonary disease (COPD), and the prevalence of panic disorder is at least 10 times higher than in the general population. In the current study, we examined resistive load perception in patients with COPD with and without panic attacks. We tested competing hypotheses, based on conflicting results of earlier studies, that those patients with COPD with panic attacks or panic disorder would show either heightened or blunted perception of dyspnea as the magnitude of inspiratory resistive loads increased. We compared 20 patients with COPD with panic attacks or panic disorder, 20 patients without panic, and 20 healthy, age-matched subjects using an inspiratory resistive load-testing protocol. We administered a diagnostic interview for panic attacks and panic disorder. We measured perceived dyspnea in response to increasing inspiratory resistive loads (modified Borg scale) and several respiratory variables. Dyspnea ratings increased linearly for all groups as the size of resistive loads increased. No significant differences were found between groups on the respiratory variables. Patients with COPD with panic attacks or panic disorder rated their level of dyspnea significantly higher than did other subjects. Patients with COPD with panic attacks showed heightened sensitivity to inspiratory loads. The result reinforces the influence of psychological factors on symptom perception in this disease.

Muscle Nerve, Mar 1, 1998

We investigated factors affecting maximal voluntary torque and the assessment of the level of vol... more 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.

Journal of Applied Physiology, Apr 1, 1986

If esophageal and chest wall recordings of diaphragmatic electromyographic activity (EMG) accurat... more If esophageal and chest wall recordings of diaphragmatic electromyographic activity (EMG) accurately reflect neural drive to this muscle, then compound muscle action potentials (CMAPs) produced by supramaximal stimulation of the phrenic nerve should not alter with changes in diaphragmatic position. Maximal CMAPs were therefore recorded 1) during changes in lung volume from near residual volume to near total lung capacity, 2) during isovolume maneuvers at different lung volumes, and 3) while subjects were lying, sitting, and standing. The areas of maximal CMAPs recorded with the gastroesophageal catheter increased 5.1 +/- 3.6 times (mean +/- SD) between these volumes, increased 2.4 +/- 1.3 times as the diaphragm descended during an isovolume maneuver (at functional residual capacity), and increased 4.4 +/- 2.4 times between the lying and standing positions. Because the stimuli were supramaximal, these changes in EMG reflect changes in the relationship between the esophageal electrodes and the diaphragmatic muscle fibers. Artifactual changes were also documented for surface electrodes on the chest wall. Because of these positional changes in maximal CMAPs, previous studies, which used integrated diaphragmatic EMG to document "reflex" changes in neural drive, should be reevaluated.

Journal of neurophysiology, 2015

Obstructive sleep apnea (OSA) is associated with significantly elevated muscle sympathetic nerve ... more Obstructive sleep apnea (OSA) is associated with significantly elevated muscle sympathetic nerve activity (MSNA), leading to hypertension and increased cardiovascular morbidity. Although little is known about the mechanisms responsible for the sympathoexcitation, we have recently shown that the elevated MSNA in OSA is associated with altered neural processing in various brain stem sites, including the dorsolateral pons, rostral ventrolateral medulla, medullary raphe, and midbrain. Given the risk associated with elevated MSNA, we aimed to determine if treatment of OSA with continuous positive airway pressure (CPAP) would reduce the elevated MSNA and reverse the brain stem functional changes associated with the elevated MSNA. We performed concurrent recordings of MSNA and blood oxygen level-dependent (BOLD) signal intensity of the brain stem, using high-resolution functional magnetic resonance imaging, in 15 controls and 13 subjects with OSA, before and after 6 mo CPAP treatment. As e...

Rationale: Patients with chronic obstructive pulmonary disease have shorter inspiratory muscles a... more Rationale: Patients with chronic obstructive pulmonary disease have shorter inspiratory muscles and higher motor unit firing rates dur- ing quiet breathing than do age-matched healthy subjects. Lung volume reduction surgery (LVRS) in patients with chronic obstruc- tive pulmonary disease improves lung function, exercise capacity, and quality of life. Objectives: We studied the effect of LVRS on length and motor unit

Respiratory Physiology & Neurobiology, 2015

There is evidence that psychological factors contribute to the perception of increased difficulty... more There is evidence that psychological factors contribute to the perception of increased difficulty of breathing in patients with chronic obstructive pulmonary disease (COPD), and increase morbidity. We tested the hypothesis that cognitive behaviour therapy (CBT) decreases ratings of perceived dyspnoea in response to resistive loading in patients with COPD. From 31 patients with COPD, 18 were randomised to four sessions of specifically targeted CBT and 13 to routine care. Prior to randomisation, participants were tested with an inspiratory external resistive load protocol (loads between 5-45 cmH20/L/s). Six months later we re-measured perceived dyspnoea in response to the same inspiratory resistive loads and compared results to measurements prior to randomisation. There was a significant 17% reduction in dyspnoea ratings across the loads for the CBT group, and no reduction for the routine care group. The decrease in ratings of dyspnoea suggests that CBT to alleviate breathing discomfort may have a role in the routine treatment of people with COPD.

NeuroImage: Clinical, 2015

16 Keywords: 42 43 44 45 46 48 complete or partial collapse of the upper airway and cessation of ... more 16 Keywords: 42 43 44 45 46 48 complete or partial collapse of the upper airway and cessation of airflow 49 during sleep. It is associated with significantly increased daytime 50 muscle sympathetic nerve activity (MSNA; Carlson et al.

Respirology (Carlton, Vic.), 2014

The prevalence of physical comorbidities such as obesity, musculoskeletal or neurological conditi... more The prevalence of physical comorbidities such as obesity, musculoskeletal or neurological conditions in people with chronic obstructive pulmonary disease (COPD) is high, yet little is known about the impact of these physical comorbidities on physical activity. The primary aim of the study was to compare the physical activity levels of people with COPD with physical comorbidities (COPD + PC) to people with COPD without physical comorbidities (COPD) and healthy age-matched volunteers (control group). Twenty-five people with COPD + PC (mean (standard deviation (SD)) age 73 (11) years, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II-IV), 25 people with COPD (70 (8) years, GOLD stage II-IV) and 25 controls (70 (7) years) wore the SenseWear Pro3 Armband for 7 days. Engagement in light intensity physical activity (1.5-3.0 metabolic equivalents (MET)) (140 (76) minutes per day (min/day)) and moderate intensity physical activity (3.0-6.0 MET) (25 (35) min/day) in the C...

Physiotherapy, 2014

Objectives Water-based exercise training is a relatively new concept in the management of people ... more Objectives Water-based exercise training is a relatively new concept in the management of people with COPD. This study aimed to examine the acceptability of the aquatic environment as a medium for exercise training in people with COPD with physical comorbidities. Design Following a supervised eight week, three times a week, water-based exercise training programme conducted in a hospital hydrotherapy pool as part of a randomised controlled trial, participants completed a questionnaire about their experience with exercise training in the pool including adverse events, barriers and factors enabling exercise programme completion, satisfaction with the aquatic environment and their preference for an exercise training environment. Results All 18 participants (mean (SD) age 72 (10) years; FEV 1 % predicted 60 (10) %) who commenced the water-based exercise training programme completed the questionnaire. Three participants withdrew from training. High acceptability of the water and air temperature, shower and change-room facilities, staff assistance and modes of pool entry was reported (94% to 100%). Six factors were highly rated as enabling exercise programme adherence and completion: staff support (chosen by 93% of participants), enjoyment (80%), sense of achievement (80%), noticeable improvements (73%), personal motivation (73%) and participant support (53%). Eighty-nine percent of the participants indicated they would continue with water-based exercise. Conclusions This study provides the first insight into the acceptability of the aquatic environment for exercise training in people with COPD and indicates water-based exercise and the aquatic environment is well accepted.

Journal of applied physiology (Bethesda, Md. : 1985), 2002

In congestive heart failure (CHF), muscle sympathetic activity (MSNA) is greatly elevated, but ou... more In congestive heart failure (CHF), muscle sympathetic activity (MSNA) is greatly elevated, but our laboratory has shown that single muscle vasoconstrictor neurons primarily fire only once per cardiac interval, as in normal subjects (Elam M and Macefield VG. J Appl Physiol 91: 717-724, 2001; Macefield VG, Rundqvist B, Sverrisdottir YB, Wallin BG, and Elam M. Circulation 100: 1708-1713, 1999). In this study, we used patients with obstructive sleep apnea syndrome (OSAS) to test the hypothesis that this firing pattern is maintained in other states of sympathoexcitation. Unitary recordings were made from muscle vasoconstrictor neurons in eight awake OSAS patients. The average firing frequency of 12 units was 0.96 Hz and the firing probability 51%, similar to previous observations in CHF patients (0.98 Hz, 55%) but higher than in healthy subjects (0.40 Hz, 31%). However, the percentages of cardiac intervals in which neurons generated one, two, three, or four spikes were 59, 27, 10, and 3%...

Journal of applied physiology (Bethesda, Md. : 1985), 2001

Single motor unit discharge was measured directly in diaphragm and parasternal intercostal muscle... more 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 activi...

Respiration physiology, Jan 3, 1999

Task failure during inspiratory resistive loading has been attributed to inspiratory muscle fatig... more 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 i...

Respiration physiology, 1996

Maximal inspiratory and transdiaphragmatic pressures vary with lung volume but the possibility th... more 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 rela...

The Journal of physiology, 1993

1. To determine whether discomfort associated with breathing (dyspnoea) is related to the chemica... more 1. To determine whether discomfort associated with breathing (dyspnoea) is related to the chemical drive to breath, three subjects were totally paralysed while fully conscious. Subjective responses to a rising CO2 stimulus were obtained during rebreathing, rebreathing with CO2 added, and breath holding. Dyspnoea was measured with a 10-point Borg scale. 2. Following nasotracheal intubation and ventilation (oxygen saturation, O2,Sat, 98-100% and end-tidal CO2, PET,CO2, 30-40 mmHg), total neuromuscular blockade was induced by a rapid injection of atracurium (> 2.5 mg kg-1) and complete paralysis was maintained with an infusion (5 mg (kg h)-1). Paralysis was confirmed by abolition of the compound muscle action potentials of both the diaphragm and abductor hallucis evoked by supramaximal electrical stimulation of the relevant nerves. Communication via finger movement was preserved for the first 20-30 min following paralysis by inflation of a sphygmomanometer cuff on one arm. 3. Before...

Thorax, 1994

Although psychological distress predicts mortality in asthma, an underlying physiological link ha... more Although psychological distress predicts mortality in asthma, an underlying physiological link has not been shown. This study examined relations between impaired voluntary drive to breathe and measures of mood states. The level of maximal voluntary activation of the diaphragm and elbow flexors was measured in a previous study using a sensitive modification of the twitch interpolation technique in 11 asthmatic and 10 control subjects. In this study psychological distress was assessed using the Profile of Mood States questionnaire and measures of distress were compared with the muscle voluntary activation results. For the asthmatic subjects, depressed mood increased the risk of impaired maximal voluntary activation of the diaphragm by 3.5 times (95% CI 1.09 to 11.3). No such association was observed in control subjects. These results suggest that depressed mood may predispose an asthmatic patient to impaired voluntary activation of the diaphragm. Such individuals would be at increased...

The Journal of physiology, Jan 15, 1995

1. This study was designed to investigate the role of airway receptors in the responses of a rang... more 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 wer...

Respiration physiology, 1983

Endurance properties of the inspiratory and expiratory muscles were compared with those of the fl... more Endurance properties of the inspiratory and expiratory muscles were compared with those of the flexors and extensors of the elbow in healthy volunteers. During a series of sustained contractions separated by rest intervals of one minute there was a progressive decline in the force produced by both muscle groups acting at the elbow and by the expiratory muscles. By contrast, the ability of the inspiratory muscles to generate force recovered completely within the one minute intervals. The decline in force during the first sustained contraction was similar for the inspiratory muscles and those acting at the elbow. During series of repeated brief maximal contractions (duty cycle 50%) the inspiratory muscles fatigued less than the other muscle groups. This apparent resistance to fatigue shown by the inspiratory muscles may be due to many factors including the central organization of their motoneurones and to local neuromuscular properties. Evidence supporting a contribution from intrinsi...