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Biomedical subjects

J Moxham

Publications and source records attributed to J Moxham.

At least 91 records · Page 5Linked to original sources

Effects of temperature on phrenic nerve and diaphragmatic function during cardiac surgery.

We have studied the effects of whole body cooling on phrenic nerve and diaphragmatic function in 26 patients using magnetic stimulation of the phrenic nerves with a pair of Magstim 200 HP stimulator coils during cardiopulmonary bypass. The diaphragmatic electromyogram in response to magnetic pulses was recorded with needle electrodes at two temperatures, approximately 31 degrees C (cold) and approximately 36 degrees C (warm) during the cooling or rewarming phase of hypothermic cardiopulmonary bypass. This 5 degrees C temperature change was associated with clear changes in the evoked electromyographical response of the diaphragm. Median latency between stimulus and electromyographic response was 10.1 (range 8.0-11.8) ms during cold and 8.3 (5.9-10.2) ms during warm stimulation (P < 0.001). Median duration of the muscle compound action potential was prolonged and its amplitude reduced in cold compared with warm stimulations (P < 0.01). These effects were enhanced by application of ice slush to the heart. We conclude that diaphragmatic function may be affected by mild hypothermia after cardiac surgery.

Adult↗

Diaphragm performance during maximal voluntary ventilation in chronic obstructive pulmonary disease.

In normal subjects 2 min of maximal voluntary hyperventilation results in failure of tension generation and low-frequency fatigue of the diaphragm. Patients with severe chronic obstructive pulmonary disease (COPD) do not develop diaphragm fatigue during exhaustive treadmill exercise despite excessive inspiratory muscle loading and we hypothesized that they might be relatively resistant to the development of diaphragm fatigue during maximal ventilation. In six patients with severe COPD (mean FEV1 0.671) we therefore loaded the diaphragm using 2 min of maximal isocapnic ventilation (MIV). Initial mean ventilation was 28.6 L/min and diaphragm pressure-time product (PTPdi) 602 cm H2O x s/min; these values were sustained throughout MIV without significant decline. Mean twitch transdiaphragmatic pressure (Tw Pdi) was 19.7 cm H2O 25 min after a control run and 20.5 cm H2O at the same time after MIV [corrected]. Compared with normal subjects previously studied in our laboratory (Hamnegard, C.-H., et al. Eur. Respir. J. 1996;9:241-247) the reduction in PTPdi was disproportionately greater than the reduction in Tw Pdi. We conclude that, unlike normal subjects, 2 min of MIV causes neither failure of diaphragm performance nor low-frequency diaphragm fatigue in patients with severe COPD. It is likely that the diaphragm makes a relatively limited contribution to the generation of maximal levels of ventilation in severe COPD.

Aged↗

The contractile properties of the elderly human diaphragm.

It has previously been reported that aging is associated with a substantial decrease in diaphragm strength. To test this hypothesis we studied 15 (10 male, 5 female) subjects with a mean age of 29 (range 21 to 40) and 15 elderly (10 male, 5 female) subjects, mean age 73 (range 67 to 81). We measured transdiaphragmatic pressure (Pdi) during a maximal sniff (Sniff Pdi) and during bilateral cervical magnetic stimulation (CMS) of the phrenic nerve roots (Tw Pdi). Additionally in 17 subjects (9 elderly and 8 young) the Pdi elicited by paired CMS (pTw Pdi) was obtained at interstimulus intervals ranging from 10 to 999 ms (1 to 100 Hz). There was considerable overlap between groups. Mean Sniff Pdi in the elderly was 119 cm H2O compared with 136 cm H2O for the young subjects; this represented a median reduction of 18 cm H2O or 13% (p = 0.05, 95% Cl of difference 0 to 33 cm H2O). Mean Twitch Pdi in the elderly was 26.8 cm H2O compared with 35.2 cm H2O, a median reduction of 8 cm H2O or 23% (p = 0.004, 95% Cl 3 to 13 cm H2O). At 10 Hz the elderly tended to generate a higher fraction of the Pdi obtained at 100 Hz than the young, but this trend did not achieve statistical significance (p = 0.11). We conclude that aging is associated with a reduction in diaphragm strength. However the magnitude of the reduction is small and may be offset by a leftward shift of the force-frequency relationship.

Adult↗

Cervical magnetic stimulation of the phrenic nerves in bilateral diaphragm paralysis.

Cervical magnetic stimulation (CMS) produces a greater twitch transdiaphragmatic pressure (TwPdi) than electrical stimulation. This may be because CMS produces rib cage muscle activation, thus producing an inspiratory action independent of the diaphragm. Alternatively, CMS could merely stiffen the rib cage, allowing the diaphragm to act efficiently, by contracting against a stable rib cage. To examine these two hypotheses we studied five patients with isolated bilateral diaphragm paralysis using CMS and bilateral electrical phrenic stimulation (BES). TwPdi, twitch esophageal pressure (TwPes), and twitch gastric pressure (TwPgas) were measured. We also assessed maximal sniff esophageal and transdiaphragmatic pressures (SnPes) (SnPdi), maximal inspiratory and expiratory mouth pressures (MIP) (MEP), and fall in VC on moving from an upright to a supine position. Respiratory muscle strength tests were consistent with bilateral diaphragm paralysis, and the MEPs confirmed normal expiratory muscle function. The patients were able to generate a mean SnPes of -30 cm H2O, mainly because of inspiratory activity of rib cage and neck muscles. However, TwPdi and TwPes during both CMS and BES were close to zero. We conclude that in our patients with diaphragm paralysis caused by neuralgic amyotrophy, CMS stiffens the rib cage but does not have an inspiratory action independent of the diaphragm.

Adult↗

Simulation of cough in man by magnetic stimulation of the thoracic nerve roots.

Normal cough requires abdominal muscle contraction. We have previously reported contraction of the abdominal muscles elicited by a single percutaneous magnetic stimulation of the thoracic nerve roots. We hypothesized that paired magnetic twitches could generate sufficient tension in the abdominal muscles to simulate cough. Therefore, six normal subjects were stimulated at the T10 intervertebral level in the seated position. We measured the gastric pressure elicited by paired magnetic stimuli (pTw Pga) with interstimulus intervals in the range of 10 ms (100 Hz) to 999 ms (1 Hz). In the second part of the study we evaluated paired stimuli (at the frequency found to produce the greatest response) using a valve to simulate the function of the glottis; the valve was arranged such that it opened once mouth pressure exceeded a predetermined threshold. Mean pTw Pga during stimulation for the 6 subjects was 74 cm H2O (range, 30-109), and mean peak flow was 209 L/min (range, 128-345 L/min). These values were increased if the subject took a prior inspiration or had previously made a vigorous expiratory effort. Comparable values for a maximal natural cough were 212 cm H2O and 649 L/min. We conclude that paired magnetic thoracic nerve root stimulation produces gastric pressure and expiratory flow of an order of magnitude comparable to a natural cough.

Abdominal Muscles↗

Paired phrenic nerve stimuli for the detection of diaphragm fatigue in humans.

The transdiaphragmatic pressure (Pdi) elicited by paired bilateral phrenic nerve stimulation may be viewed as the sum of the Pdi values produced by the first (t1) and second (t2) stimulus. The Pdi at t2 (P[di,t2]) is a function of the interstimulus interval. A reduction in the ratio obtained by dividing Pdi,t2 at 10 Hz (P[di,t2,10]) by Pdi at 100 Hz (P[di,t2,100]) (t2(10:100)) has been proposed as a test of low frequency diaphragm fatigue. The aim of the present study was to establish whether this change could also be detected using paired cervical magnetic nerve stimulation (pCMS), and whether t2(10:100) was influenced by lung volume. We studied healthy subjects at functional residual capacity (FRC), at 0.5 and 1.0 L below FRC, and at 0.5, 1.0 and 1.5 L above FRC. The subjects were then subjected to a fatiguing protocol (2 min of maximal isocapnic ventilation (MIV)). Studies were repeated at FRC 20 and 60 min after MIV and between these times at 1.0 L below and 1.5 L above FRC. In the unfatigued state, t2(10:100) had a negative relationship with increasing lung volume (r2=0.98, p=0.002). After MIV there was a fall in the Pdi elicited by a single stimulus (mean fall at 20 min 17.9% and at 60 min 14.6%, p<0.03 for both). t2(10:100) fell by a mean 28.1% after 20 min and mean 22.9% at 60 min (p<0.03 for both). This change was mainly mediated by a fall in the P[di,t2,10]. The t2(10:100) was not able to distinguish between fatigue and acute hyperinflation. We conclude that paired cervical magnetic nerve stimulation may be used to detect low frequency diaphragm fatigue but that it remains important to control for lung volume.

Adult↗

Quadriceps strength and fatigue assessed by magnetic stimulation of the femoral nerve in man.

There is no nonvolitional method of assessing quadriceps strength which both supramaximally activates the muscle and is acceptable to subjects. In 10 normal subjects and 10 patients with suspected muscle weakness we used magnetic stimulation of the femoral nerve to elicit an isometric twitch and measured twitch tension (TwQ), surface electromyogram in addition to the maximum voluntary contraction force (MVC). Supramaximality was achieved in all subjects at a mean of 83% of maximum stimulator output. When supramaximal, TwQ was reproducible (mean coefficient of variation 3.6%, range 0.7-10.9) and correlated well with MVC (r2 = 0.83, P<0.001). In 7 normal subjects we measured TwQ before and after a fatiguing protocol; after 20 min TwQ was a mean of 55% (range 29-77%) of baseline and remained substantially reduced at 90 min. Magnetic femoral nerve stimulation is a painless, supramaximal method of assessing quadriceps strength and fatigue which is likely to be of value in clinical and physiological studies.

Action Potentials↗

Clinical assessment of diaphragm strength by cervical magnetic stimulation of the phrenic nerves.

BACKGROUND: Accurate assessment of diaphragm strength can be difficult. Transdiaphragmatic pressure (PDI) measurements during volitional manoeuvres are useful but it may be difficult to ensure maximum patient effort. Magnetic stimulation of the phrenic nerves is easy to perform and the results are reproducible in normal subjects. The purpose of the present study was to evaluate the usefulness of magnetic stimulation of the phrenic nerves in the assessment of diaphragm weakness in patients. METHODS: Sixty-six patients referred for assessment of respiratory muscle strength and 23 normal subjects were studied. Twitch PDI (TwPDI) following magnetic stimulation of the phrenic nerves and sniffPDI were obtained in all individuals. TWPDI following bilateral electrical stimulation of the phrenic nerves was also obtained in eight patients. RESULTS: Mean (SD) TwPdi for the normal subjects was 31 (6) cm H2O and 18 (11) cm H2O for the patients. TwPDI and sniffPDI were correlated (r = 0.77). Seven of the 37 patients (19%) with a reduced sniffPDI had a TwPDI within the normal range whereas two of the 32 patients (6%) with a reduced TwPDI had a normal sniffPDI. TwPDI was similar with magnetic and electrical stimulation. CONCLUSIONS: TwPDI following magnetic stimulation of the phrenic nerves is a clinically useful measurement when assessing diaphragm weakness.

Adult↗

Effect of maximum ventilation on abdominal muscle relaxation rate.

BACKGROUND: When the demand placed on the respiratory system is increased, the abdominal muscles become vigorously active to achieve expiration and facilitate subsequent inspiration. Abdominal muscle function could limit ventilatory capacity and a method to detect abdominal muscle fatigue would be of value. The maximum relaxation rate (MRR) of skeletal muscle has been used as an early index of the onset of the fatiguing process and precedes failure of force generation. The aim of this study was to measure MRR of abdominal muscles and to investigate whether it slows after maximum isocapnic ventilation (MIV). METHODS: Five normal subjects were studied. Each performed short sharp expiratory efforts against a 3 mm orifice before and immediately after a two minute MIV. Gastric pressure (PGA) was recorded and MRR (% pressure fall/10 ms) for each PGA trace was determined. RESULTS: Before MIV the mean (SD) maximum PGA MRR for the five subjects was 7.1 (0.8)% peak pressure fall/10 ms. Following MIV mean PGA MRR was decreased by 30% (range 25-35%), returning to control values within 5-10 minutes. CONCLUSIONS: The MRR of the abdominal muscles, measured from PGA, is numerically similar to that described for the diaphragm and other skeletal muscles. After two minutes of maximal isocapnic ventilation abdominal muscle MRR slows, indicating that these muscles are sufficiently heavily loaded to initiate the fatiguing process.

Abdominal Muscles↗

Effect of L-arginine on renal blood flow in normal subjects and patients with hypoxic chronic obstructive pulmonary disease.

BACKGROUND: L-arginine is the precursor of endothelium derived nitric oxide (NO) and increasing the available substrate may increase the production of NO. This has been shown by local infusion in peripheral vascular beds but there are few studies of the effects during systemic infusion. Renal vasoconstriction is known to be important in the pathogenesis of cor pulmonale in patients with hypoxic chronic obstructive pulmonary disease (COPD). The effects of a systemic infusion of L-arginine on renal and aortic haemodynamics were therefore investigated in normal subjects and in patients with hypoxic COPD. METHODS: Ten normal volunteers were recruited from the research staff of King's College Hospital Six patients with COPD and hypoxia (arterial oxygen tension (PaO2) < 8.5 kPa) were recruited from the thoracic medicine outpatient clinic at King's College Hospital and five age and sex matched normal subjects were recruited from a group of normal subjects recruited from the database of the Department of Health Care for the Elderly as volunteers for medical research. There was no history of renal, cardiac, or hepatic disease. Baseline values of time averaged mean of the maximum instantaneous velocity (Tamx) and maximum velocity (Vmax) of blood flow in intrarenal arteries were obtained using colour flow Doppler ultrasound. Using the same technique, Vmax was obtained from the abdominal aorta just distal to the xiphisternum before and after infusion of L-arginine via a large peripheral vein (20 g in 100 ml sterile water over 30 minutes). RESULTS: In normal subjects L-arginine increased blood velocity in the intrarenal vessels from a mean of 0.22 m/s to 0.26 m/s, an increase of 19.8%. There was no effect on arterial blood pressure, heart rate, or aortic blood velocity. L-arginine had no effect on intrarenal or aortic blood velocity in patients with hypoxic COPD. In age matched controls L-arginine increased blood velocity in the intrarenal vessels from a mean of 0.20 m/s to 0.26 m/s, an increase of 36.8%. There was no effect on arterial blood pressure, heart rate, or aortic blood velocity. CONCLUSIONS: L-arginine, at the doses administered, increased renal blood flow, as assessed by renal arterial velocity. This effect was not seen in patients with hypoxic COPD but was present in age matched controls. This suggests that the abnormal renal vascular control seen in hypoxic patients with COPD may reflect a disturbance of the L-arginine/nitric oxide pathway.

Aged↗

Abdominal muscle fatigue after maximal ventilation in humans.

Abdominal muscles are the principal muscles of active expiration. To investigate the possibility of abdominal muscle low-frequency fatigue after maximal ventilation in humans, we stimulated the nerve roots supplying the abdominal muscles. We used a magnetic stimulator (Magstim 200) powering a 90-mm circular coil and studied six normal subjects. To assess the optimum level of stimulation and posture, we stimulated at each intervertebral level between T7 and L1 in the prone, supine, and seated positions. At T10, we used increasing power outputs to assess the pressure-power relationship. Care was taken to avoid muscle potentiation. Twitch gastric pressure (Pga) was recorded with a balloon-tipped catheter. Mean (+/-SD) baseline twitch Pga measured with the subjects in the prone position at T10 was 23.5 +/- 5.4 cmH2O. Within-occasion mean twitch Pga coefficient of variation was 4.6 +/- 1.1%. Twitch Pga was measured with the subjects in the prone position with stimulation over T10 before and after 2 min of maximal isocapnic ventilation (MIV). Twenty minutes after MIV, mean twitch Pga fell by 17 +/- 9.1% (P = 0.03) and remained low 90 min after MIV. We conclude that after maximal ventilation in humans there is a reduction of twitch Pga and, therefore, of low-frequency fatigue in abdominal muscles.

Abdominal Muscles↗

Exhaustive exercise slows inspiratory muscle relaxation rate in chronic obstructive pulmonary disease.

The excessive load placed on inspiratory muscles when patients with COPD exercise could lead to fatigue and contribute to exercise limitation. Slowing of maximal relaxation rate (MRR) of skeletal muscle is an early index of the fatiguing process. We investigated whether inspiratory muscle MRR slows when patients with COPD walk to exhaustion. We studied nine well-trained and motivated patients with stable severe COPD (mean FEV1: 0.7 L, 28% predicted). Each subject performed sniff maneuvers before and after walking on a treadmill until they were forced to stop because of dyspnea. Esophageal (Pes), gastric, and transdiaphragmatic pressures were measured using balloon-tipped catheters. MRR was calculated as the percent Pes drop/10 ms. In the first minute after exercise there was a mean decrease of Pes MRR of 42% (range, 21 to 65%) (p < 0.01), which returned to baseline within 3 to 5 min. The fall in MRR indicates that the inspiratory muscles of patients with COPD walking to exhaustion are sufficiently heavily loaded to initiate the fatiguing process.

Aged↗

Bilateral magnetic stimulation of the phrenic nerves from an anterolateral approach.

We investigated whether bilateral magnetic stimulation of the phrenic nerves from an anterolateral approach (BAMPS) could combine the reproducibility and ease of use of cervical magnetic stimulation (CMS) with the specificity of bilateral electrical stimulation (BES) and whether it could be used in supine subjects. We placed two double 43-mm coils over the phrenic nerves in the neck. BAMPS produced supramaximal phrenic stimulation by electromyogram (EMG) assessment in six of seven subjects. There was no significant difference in the twitch gastric pressure/twitch esophageal pressure ratio (twitch Pgas/Pes) between BAMPS (1.2) and BES (1.3). Both differed from CMS (0.9, p < 0.001). The effect of a change in posture on twitch transdiaphragmatic pressure (TwPdi) and Pgas/Pes ratio was the same for BAMPS and BES. In normal subjects and patients BAMPS correlated significantly with BES (r = 0.97), maximal sniffs (r = 0.85), and CMS (r = 0.92). The mean difference between BAMPS and BES was 0.3 cm H2O (SD = 2.3). Two-minute maximal isocapnic ventilation produced a 19% fall in TwPdi elicited by BAMPS. BAMPS is easy, well tolerated and can be used in the supine subject. TwPdi and partitioning of Pes and Pgas were very close for BAMPS and BES, suggesting similar specificity for the diaphragm.

Case-Control Studies↗

Inspiratory pressure support reduces slowing of inspiratory muscle relaxation rate during exhaustive treadmill walking in severe COPD.

When patients with COPD walk to a state of intolerable dyspnea, there is excessive inspiratory muscle loading, as evidenced by slowing of the maximum relaxation rate of the inspiratory muscles, measured from esophageal pressure during a sniff (Sn Pes MRR). In this setting, inspiratory pressure support (IPS) delivered via an orofacial mask increases walking distance and reduces dyspnea, but the mechanism by which this benefit is achieved remains unclear. In this study we compared Sn Pes MRR after equidistant treadmill walking in six men with severe COPD (mean FEV1: 0.6 L, 22% predicted). After the free walk there was a mean slowing of Sn Pes MRR of 41% (p < 0.03). After the IPS-assisted walks, the slowing of Sn Pes MRR was 20% of baseline; this was significantly less than after the free walk (p < 0.05). Four subjects performed shorter walks; after free walks of one third and two thirds of maximum distance, the mean slowing of Sn Pes MRR was 23% and 28%, respectively. We conclude that when patients with COPD walk to exhaustion, IPS reduces slowing of inspiratory muscle MRR, and that this represents a considerable unloading of the inspiratory muscles. The magnitude of the reduction is approximately the same as reducing the distance walked by two thirds.

Aged↗

Diaphragm strength in chronic obstructive pulmonary disease.

The diaphragm is normally the main inspiratory muscle and diaphragm strength in chronic obstructive pulmonary disease (COPD) is therefore of interest. We assessed diaphragm strength in 20 patients with severe stable COPD (mean FEV1 0.61, mean thoracic gas volume [Vtg] 5.31) and seven normal control subjects, measuring both maximal sniff transdiaphragmatic pressure (sniff Pdi(max)) and twitch transdiaphragmatic pressure (Tw Pdi) elicited by cervical magnetic stimulation (CMS) of the phrenic nerve roots at FRC. Acute-on-chronic hyperinflation was examined in four patients. Mean Tw Pdi in patients and control subjects was 18.5 cm H2O and 25.4 cm H2O, respectively (p < 0.01), and mean sniff Pdi was 81.9 cm H2O and 118 cm H2O, respectively (p < 0.001). Reduction in mean intrathoracic pressures was more marked; twitch esophageal pressure (Tw Pes) was -7.3 cm H2O and -16.3 cm H2O, respectively (p < 0.001) and sniff Pes was -67 cm H2O and -97.8 cm H2O (p < 0.001). During acute-on-chronic hyperinflation there was a linear negative correlation of Tw Pdi with increasing lung volume of 3.5 cm H2O/L. The ability of the diaphragm to generate transdiaphragmatic, and particularly a negative intrathoracic, pressure is reduced in COPD and these changes are exaggerated with acute-on-chronic hyperinflation.

Aged↗

Diaphragm fatigue following maximal ventilation in man.

When highly motivated normal subjects perform maximal isocapnic ventilation, a substantial fall in ventilation is observed during the first minute associated with slowing of the maximum relaxation rate (MRR) of the inspiratory muscles. This suggests that these muscles are excessively loaded, raising the possibility that overt contractile failure of the diaphragm contributes to the fall in ventilation. We therefore investigated the effect of maximal isocapnic ventilation (MIV) on twitch transdiaphragmatic pressure (Pdi,Tw) elicited by cervical magnetic stimulation. We measured Pdi,Tw before and after 2 min MIV in nine normal subjects. Initial mean (SD) ventilation for the nine subjects was 196 (15) L.min-1 falling by 35% at 1 min. Pdi,Tw fell following MIV, at 10 min was reduced by 24%, and remained substantially reduced 90 min after MIV. No change in Pdi,Tw was observed during control studies in which subjects were studied with the same protocol but omitting MIV. We conclude that diaphragmatic contractility is reduced after 2 min maximal isocapnic ventilation and diaphragmatic fatigue may be a limiting factor in maximal ventilation in man.

Adult↗

Respiratory muscle testing.

When addressing the question of whether or not the respiratory muscles are weak, and quantifying exactly how severe any weakness might be, it is sensible to regard the tests available as complimentary, and to proceed by using simple tests first and invasive tests only when appropriate. This sequential and complimentary approach is illustrated in table 1. Thus, if the supine vital capacity is normal, it is very unlikely that there is clinically significant respiratory muscle weakness. However, if the vital capacity is low, it may then be appropriate to measure the maximal inspiratory and maximal expiratory pressures. If the mouth pressures are normal, weakness has been excluded, but if the pressures are low it will then be necessary to proceed to the next tests on the list. Thus, the process continues and, when all of the tests have been performed, a comprehensive description can be achieved of any respiratory muscle weakness that is present. We now have the capacity, if we so wish, to measure respiratory muscle weakness accurately. The challenge is to use these techniques to demonstrate the undoubted importance of respiratory muscle weakness in a wide variety of clinical circumstances.

Humans↗