M Green

Potentiation of diaphragmatic twitch after voluntary contraction in normal subjects.

BACKGROUND--Skeletal muscle twitch responses may be transiently increased by previous contractions, a phenomenon termed twitch potentiation. The aim of this study was to examine the extent and time course of diaphragmatic twitch potentiation and its relationship to both the magnitude and duration of the preceding voluntary diaphragmatic contraction. METHODS--Twitch transdiaphragmatic pressure (PDI) was measured in six normal subjects, before and after voluntary diaphragm contractions of 100%, 75%, 50%, and 25% of maximum PDI (PDImax) sustained for five and 10 seconds. RESULTS--Twitch PDI was significantly increased after 100%, 75%, and 50% contractions. Following maximal contractions sustained for 10 seconds the mean increase in twitch PDI was 52%. Following 50% contractions sustained for five seconds the mean increase in twitch height was 28%. In all runs twitch PDI returned to rested levels within 20 minutes. CONCLUSIONS--Twitch potentiation can be substantial, even following submaximal contractions, and must be taken into account when twitch pressure is used to assess diaphragm contractility.

Portable measurement of maximum mouth pressures

We have compared a small portable mouth pressure meter (MPM) to our laboratory standard (LS) pressure recording equipment in order to evaluate this new device. The mouth pressure meter measures and displays as a digital read-out peak pressure for inspiratory and expiratory efforts. It samples the signal at 16 Hz, and an integral microprocessor is programmed to determine and display the maximum pressure averaged over one second both during inspiratory and expiratory manoeuvres (PImax and PEmax, respectively). A fine bore catheter connecting the mouthpiece of the mouth pressure meter to a Validyne pressure transducer enabled simultaneous measurement of pressure, which was analysed by LabVIEW, running on a Macintosh Quadra 700 computer. We studied 13 normal subjects and 11 patients with respiratory disease. Each subject performed inspiratory and five expiratory efforts. The values displayed from the mouth pressure meter were manually recorded. The mouth pressure meter reliably and accurately measured peak pressure and maximal pressure both for inspiratory and expiratory efforts in normals and patients. The mean +/- SD difference when compared with the Validyne method was 0.19 +/- 0.12 and -0.04 +/- 0.12 kPa, for PImax and PEmax, respectively. This portable device should be useful to measure mouth pressures, not only in the routine lung function laboratory but also at the bedside and in the clinic.

Unilateral magnetic stimulation of the phrenic nerve.

BACKGROUND--Electrical stimulation of the phrenic nerve is a useful non-volitional method of assessing diaphragm contractility. During the assessment of hemidiaphragm contractility with electrical stimulation, low twitch transdiaphragmatic pressures may result from difficulty in locating and stimulating the phrenic nerve. Cervical magnetic stimulation overcomes some of these problems, but this technique may not be absolutely specific and does not allow the contractility of one hemidiaphragm to be assessed. This study assesses both the best means of producing supramaximal unilateral magnetic phrenic stimulation and its reproducibility. This technique is then applied to patients. METHODS--The ability of four different magnetic coils to produce unilateral phrenic stimulation in five normal subjects was assessed from twitch transdiaphragmatic pressure (TwPDI) measurements and diaphragmatic electromyogram (EMG) recordings. The results from magnetic stimulation were compared with those from electrical stimulation. To determine whether the magnetic field affects the contralateral phrenic nerve as well as the intended phrenic nerve, EMG recordings from each hemidiaphragm were compared during stimulation on the same side and the opposite side relative to the recording electrodes. The EMG recordings were made from skin surface electrodes in five normal subjects and from needle electrodes placed in the diaphragm during cardiac surgery in six patients. Similarly, the direction of hemidiaphragm movement was evaluated by ultrasonography. To determine the usefulness of the technique in patients the 43 mm mean diameter double coil was used in 54 patients referred for assessment of possible respiratory muscle weakness. These results were compared with unilateral electrical phrenic stimulation, maximum sniff PDI, and TwPDI during cervical magnetic stimulation. RESULTS--In the five normal subjects supramaximal stimulation was established for eight out of 10 phrenic nerves with the 43 mm double coil. Supramaximal unilateral magnetic stimulation produced a higher TwPDI than electrical stimulation (mean (SD) 13.4 (2.5) cm H2O with 35 mm coil; 14.1 (3.8) cm H2O with 43 mm coil; 10.0 (1.7) cm H2O with electrical stimulation). Spread of the magnetic field to the opposite phrenic nerve produced a small amplitude contralateral diaphragm EMG measured from skin surface electrodes which reached a mean of 15% of the maximum EMG amplitude produced by ipsilateral stimulation. Similarly, in six patients with EMG activity recorded directly from needle electrodes, the contralateral spread of the magnetic field produced EMG activity up to a mean of 3% and a maximum of 6% of that seen with ipsilateral stimulation. Unilateral magnetic stimulation of the phrenic nerve was rapidly achieved and well tolerated. In the 54 patients unilateral magnetic TwPDI was more closely related than unilateral electrical TwPDI to transdiaphragmatic pressure produced during maximum sniffs and cervical magnetic stimulation. Unilateral magnetic stimulation eliminated the problem of producing a falsely low TwPDI because of technical difficulties in locating and adequately stimulating the nerve. Eight patients with unilateral phrenic nerve paresis, as indicated by a unilaterally elevated hemidiaphragm on a chest radiograph and maximum sniff PDI consistent with hemidiaphragm weakness, were all accurately identified by unilateral magnetic stimulation. CONCLUSIONS--Unilateral magnetic phrenic nerve stimulation is easy to apply and is a reproducible technique in the assessment of hemidiaphragm contractility. It is well tolerated and allows hemidiaphragm contractility to be rapidly and reliably assessed because precise positioning of the coils is not necessary. This may be particularly useful in patients. In addition, the anterolateral positioning of the coil allows the use of the magnet in the supine patient such as in the operating theatre or intensive care unit.

Mouth pressure in response to magnetic stimulation of the phrenic nerves.

BACKGROUND--Diaphragm strength can be assessed by the measurement of gastric (TW PGA), oesophageal (TW POES), and transdiaphragmatic (TW PDI) pressure in response to phrenic nerve stimulation. However, this requires the passage of two balloon catheters. A less invasive method of assessing diaphragm contractility during stimulation of the phrenic nerves would be of clinical value. A study was undertaken to determine whether pressure measured at the mouth (TW PM) during magnetic stimulation of the phrenic nerves accurately reflects TW POES, and to investigate the relations between TW PM and TW PDI; and also to see whether glottic closure and twitch potentiation can be avoided during these measurements. METHODS--Eight normal subjects and eight patients with suspected respiratory muscle weakness without lung disease were studied. To prevent glottic closure magnetic stimulation of the phrenic nerves was performed at functional residual capacity during a gentle expiratory effort against an occluded airway incorporating a small leak. TW PDI, TW POES, and TW PM were recorded. Care was taken to avoid potentiation of the diaphragm. RESULTS--In normal subjects mean TW PM was 13.7 cm H2O (range 11.3-16.1) and TW POES was 13.3 cm H2O (range 10.4-15.9) with a mean (SD) difference of 0.4 (0.81) cm H2O. In patients mean TW PM was 9.1 cm H2O (range 0.5-18.2) and TW POES was 9.3 (range 0.7-18.7) with a mean (SD) difference of -0.2 (0.84) cm H2O. The relation between TW PM and TW PDI was less close but was well described by a linear function. In patients with diaphragm weakness (low sniff PDI) TW PM was < 10 cm H2O. CONCLUSIONS--TW PM reliably reflects TW POES and can be used to predict TW PDI in normal subjects and patients without lung disease. TW PM may therefore be a promising non-invasive, non-volitional technique for the assessment of diaphragm strength.

Measurement of sniff nasal and diaphragm twitch mouth pressure in patients.

BACKGROUND: Inspiratory muscle weakness is a recognised cause of unexplained dyspnoea. It may be suggested by the finding of a low static inspiratory mouth pressure (MIP), but MIP is a difficult test to perform, with a wide normal range; a low MIP may also occur if the patient has not properly performed the manoeuvre. Further investigation conventionally requires balloon catheters to obtain oesophageal (Poes) and transdiaphragmatic pressure (Pdi) during sniffs or phrenic nerve stimulation. Two non-invasive tests of inspiratory muscle strength have recently been described--nasal pressure during a maximal sniff (Sn Pnas) and mouth pressure during magnetic stimulation of the phrenic nerves (Tw Pmo). The use of these two tests in combination might identify patients without inspiratory muscle weakness who are unable to produce a satisfactory MIP< therefore avoiding the need for investigation with balloon catheters. METHODS: Thirty consecutive patients with clinically suspected inspiratory muscle weakness and a low MIP underwent both conventional (Sn Poes and Tw Pdi) and non-invasive testing (Sn Pnas and Tw Pmo). Weakness was considered to be excluded by a Sn Poes of > or = 80 cm H20 or a Tw Pdi of > or = 20 cm H20. The limit values used to test the hypothesis were Sn Pnas > or = 70 cm H20 or Tw Pmo > or = 12 cm H20. RESULTS: Inspiratory muscle weakness was excluded in 17 of the 30 patients. Fifteen of these would have been identified using Sn Pnas and Tw Pmo, with better results when the two tests were combined. The cut off values selected for Sn Pnas and Tw Pmo were shown by ROC plots to indicate normal strength conservatively, avoiding failure to detect mild degrees of weakness. No patient with global weakness was considered normal by Sn Pnas or Tw Pmo. CONCLUSIONS: In most patients with normal inspiratory strength and a low MIP, Tw Pmo and Sn Pnas used in combination can reliably exclude global inspiratory muscle weakness, reducing the number of patients who need testing with balloon catheters.

Anterior magnetic phrenic nerve stimulation: laboratory and clinical evaluation

Objective: Anterior magnetic stimulation (aMS) of the phrenic nerves is a new method for the assessment of diaphragm contractility that might have particular applications for the clinical assessment of critically ill patients who are commonly supine. Design: We compared aMS with existing techniques for measurement of diaphragm weakness and fatigue in 10 normal subjects, 27 ambulant patients with suspected diaphragm weakness and 10 critically ill patients. Setting: Laboratory and intensive care unit of two university hospitals. Results: Although aMS was not demonstrably supramaximal in normal subjects, the mean value of twitch transdiaphragmatic pressure (Tw Pdi) obtained at 100 % of stimulator output, 23.7 cmH2O, did not differ significantly from that obtained with bilateral supramaximal electrical stimulation (ES), 24.9 cmH2O, or bilateral anterior magnetic phrenic nerve stimulation (BAMPS), 27.3 cmH2O. A fatiguing protocol produced a 20 % fall in aMS-Tw Pdi and a 19 % fall in BAMPS-Tw Pdi; the fall in aMS-Tw Pdi correlated with the fall in BAMPS-Tw Pdi (r2 = 0.84, p = 0.03) indicating that aMS can detect diaphragm fatigue. In ambulant patients aMS agreed closely with existing measures of diaphragm strength. The maximal sniff Pdi correlated with both the aMS-Tw Pdi (r2 = 0.60, p < 0.0001) and the BAMPS-Tw Pdi (r2 = 0.65, p < 0.0001) and the aMS-Tw Pdi was a mean (SD) 2.2 (4.3) cmH2O less than BAMPS-Tw Pdi. In addition, aMS correctly identified diaphragm dysfunction in patients studied on the ICU. Conclusions: We conclude that aMS is of clinical value for the investigation of suspected diaphragm weakness.

A novel clinical test of respiratory muscle endurance

Impaired respiratory muscle endurance (RME) could reduce exercise tolerance and contribute to ventilatory failure. The aim of the present study was to develop a clinically-feasible method to measure RME using negative-pressure inspiratory-threshold loading. It was hypothesized that endurance time (tlim) could be predicted by normalizing oesophageal pressure-time product (PTP) per total breath cycle (PTPoes) for maximum oesophageal pressure (Poes,max); the load/capacity ratio. The corresponding mouth pressures, PTPmouth and Pmouth,max were also measured. The RME test was performed on 30 healthy subjects exposed to the same target pressure (70% of Poes,max). Eight patients with systemic sclerosis/interstitial lung disease were studied to assess the validity and acceptability of the technique. Normal subjects showed a wide intersubject variation in tlim (coefficient of variation, 69%), with a linear relationship demonstrated between log tlim and PTPoes/Poes,max (r=0.88). All patients with systemic sclerosis/interstitial lung disease had normal respiratory muscle strength, but six out of eight had a reduction in RME. In conclusion, endurance time can be predicted from the load/capacity ratio, over a range of breathing strategies; this relationship allows abnormal respiratory muscle endurance to be detected in patients. Oesophageal and mouth pressure showed a close correlation, thus suggesting that the test could be applied noninvasively.

Inspiratory muscle relaxation rate assessed from sniff nasal pressure.

BACKGROUND--Slowing of the maximum relaxation rate (MRR) of inspiratory muscles measured from oesophageal pressure (POES) during sniffs has been used as an index of the onset and recovery of respiratory muscle fatigue. The purpose of this study was to measure MRR at the nose (PNASAL MRR), to investigate its relationship with POES MRR, and to establish whether PNASAL MRR slows with respiratory loading. METHODS--Five normal subjects were studied. Each performed sniffs before and after two minutes of maximal isocapnic ventilation (MIV). In a separate session the subjects performed submaximal sniffs. POES and PNASAL were recorded during sniffs and the MRR (% pressure fall/10 ms) for each sniff was determined. RESULTS--Before MIV mean POES MRR was 8.9 and PNASAL MRR was 9.3. The mean (SD) difference between PNASAL MRR and POES MRR during a maximal sniff was 0.48 (0.34) (n = 64) and during submaximal sniffs was 0.28 (0.46) (n = 526). The subjects showed a mean decrease in sniff POES MRR of 27.4% (range 22.5-36%) after MIV and a similar reduction in sniff PNASAL MRR of 28.5% (range 24.1-41.3%). Both returned to control values within 5-10 minutes. CONCLUSIONS--PNASAL MRR reflects POES MRR over a wide range of sniff pressures, PNASAL MRR of maximal sniffs reflects POES MRR in normal subjects at rest and following MIV, so measurement of PNASAL MRR may be a useful non-invasive method for measuring inspiratory muscle MRR, thereby providing an index of respiratory muscle fatigue.

The case against inspiratory muscle training in COPD

Despite maximal medical therapy, many chronic obstructive pulmonary disease (COPD) patients remain breathless and this has led to persistent and commendable efforts to reduce symptoms and improve exercise performance using nonpharmacological approaches; some of these, for example pulmonary rehabilitation (PR) 1, comprising general exercise and fitness training, are of proven benefit, while others remain controversial. Inspiratory muscle training (IMT), being cheap and free of side-effects, is intuitively attractive, since improving the capacity of the inspiratory muscles should “make breathing easier” and so improve exercise performance. Enthusiasts do not allow the superficial attractiveness of this proposition to be clouded by aspects of the data. These are that the diaphragm is already working hard and well trained in emphysema, with a shift towards fatigue resistant type I fibres 2, that at a single fibre level it is energetically more efficient 3, that (allowing for hyperinflation) it is not actually weak 4, 5 and that diaphragm fatigue cannot be elicited in patients in vivo 6, 7, even when patients are sufficiently ill to require mechanical ventilation 8. The question of whether the respiratory muscles are weak in COPD seems particularly important in the context of IMT. In the current issue of the European Respiratory Journal , Gosselink et al. 9 cite our paper 5 as evidence that the diaphragm is weak; in fact, we concluded that the major reason for the reduced transdiaphragmatic pressures observed in COPD was hyperinflation, which of course would not be expected to improve with IMT. They also state that inspiratory …

Central fatigue of the diaphragm and quadriceps during incremental loading

Anecdotal observations suggest that low frequency fatigue, as judged by a fall in twitch tension, is more difficult to achieve in the diaphragm than nonrespiratory muscle but this hypothesis has not previously been directly tested. We studied 7 subjects by performing incremental repetitive contraction loading protocols of the diaphragm and quadriceps. We measured twitch transdiaphragmatic pressure (Tw Pdi) and twitch quadriceps tension (Tw Q) during both muscle contraction and relaxation phases during the run. Unpotentiated and potentiated Tw Pdi and Tw Q were measured before and at 20, 40, and 60 minutes after the run. During the run, greater activation of the quadriceps was achieved; for example, at 70% of maximal voluntary effort the interpolated Tw Q was 12.5% of the relaxation phase Tw Q (implying activation of 87.5%) compared with 29.4% (i.e., 70.6% activation) for the diaphragm (p = 0.05). A significantly greater fall in Tw Q than Tw Pdi was observed (unpotentiated Tw Pdi at 20 minutes 94% baseline versus Tw Q 59% baseline, p = 0.007). Low frequency fatigue in humans is more difficult to generate in the diaphragm than in the quadriceps muscle due in part to reduced central activation.