Background: Reduced diaphragm contractility occurs in some healthy subjects when they exercise to exhaustion. This indicates low frequency fatigue, which may contribute to task failure. We hypothesised that patients with congestive heart failure (CHF) might be especially vulnerable to the development of low frequency diaphragm fatigue after exhaustive exercise.Aims: To study the effect of exhaustive incremental cycle exercise on diaphragm contractility in patients with CHF.Methods: 12 patients with CHF with an ejection fraction of 36.5 +/- 7.3% and 12 healthy age-matched control subjects performed an incremental cycle test to exhaustion. The unpotentiated twitch transdiaphragmatic pressure (twitch Pdi) in response to bilateral anterolateral magnetic phrenic nerve stimulation (BAMPS) was measured before and after exercise.Results: Twitch Pdi at baseline was 20.2 +/- 6.7 cmH(2)O in the CHF group and 20.3 +/-.3 cmH(2)O in the controls (p=0.957). 25 and 35 min post exercise the values were 19.9 +/- 5.4 and 20.0 +/- 5.1 cmH(2)O in the CHF group and 20.6 +/- 4.3 and 21.2 +/- 3.4 cmH(2)O in the control group; neither change was significant (F(2,27)=0.007, p=0.993; F(2,33)=0.144, p=0.866, respectively).Conclusion: When patients with CHF cycle to exhaustion, low frequency fatigue of the diaphragm does not occur, and this is unlikely to be an important factor limiting exercise capacity of such patients. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

The costal and crural parts of the diaphragm differ in their embryological development and physiological function. It is not known if this is reflected in differences in their motor cortical representation. We compared the response of the costal and crural diaphragms using varying intensities of transcranial magnetic stimulation of the motor cortex at rest and during submaximal and maximal inspiratory efforts. The costal and crural motor evoked potential recruitment curves during submaximal inspiratory efforts were similar. The response to stimulation before, during and at 10 and 30 min after 44 consecutive maximal inspiratory efforts was also the same. Using paired stimulations to investigate intra-cortical facilitatory and inhibitory circuits we found no difference between the costal and crural response with varying interstimulus intervals, or when conditioning and test stimulus intensity were varied. We conclude that supraspinal control of the costal and crural diaphragm is identical during inspiratory tasks.

PURPOSE:To investigate the effects of environmental temperature and the diurnal increase in body temperature on muscle contractile processes, 11 male subjects performed maximal and submaximal isometric contractions of the knee extensors with recording of the electromyographic activity in four different conditions (morning/neutral, morning/moderately warm and humid, afternoon/neutral, and afternoon/moderately warm and humid). METHODS:The morning experiments were conducted between 0700 and 1900 h, and the afternoon experiments were conducted between 0500 and 0700 h. The mean laboratory temperatures and humidity were 20.5 (+/-1) degrees C + 67 (+/-4)% and 29.5 (+/-0.8) degrees C + 74 (+/-10)% for the neutral and moderately warm and humid conditions, respectively. RESULTS:Results showed a significant diurnal increase in both rectal and skin temperatures whatever the environmental conditions, and an increase in the skin temperature after a 60-min moderately warm exposure. The major finding of this study was an interaction effect of time of day and environmental conditions on the force/electromyographic activity ratio. That suggests that skeletal muscle contractility was differently increased by the passive warm-up effect of a moderately warm exposure, depending on the diurnal variation in body temperature. This conclusion is supported by an increase in force in the morning only after a 60-min warm exposure (+19%) and in a neutral environment only with the diurnal increase in body temperature (+12%). CONCLUSION:In summary, our data showed that both the warm exposure and the diurnal increase in body temperature influence muscle contractility and consequently muscle strength. However, the improvement in muscle contractility after these two passive warm-ups cannot be combined in order to improve force to a greater level.

The present investigation was intended to assess the consequences of an inspiratory load on the diaphragm central component of fatigue during exercise. We recorded the motor potential evoked (MEP) by transcranial magnetic stimulation of the motor cortex in 10 subjects. The diaphragm and rectus femoris were studied before and 10, 20, and 40 min after two 16-min cycling exercise (E) trials requiring 55% of maximal oxygen uptake: 1) one with an inspiratory threshold load (E + ITL), corresponding to 10% of maximal inspiratory pressure; and 2) the other without the load (E). Dyspnea, heart rate, electromyographic activity of the sternocleidomastoid, and diaphragm work were significantly higher in E + ITL than in E. Neither trial affected the response to phrenic magnetic stimulation, which was performed 15 and 25 min postexercise, or the maximal inspiratory pressure (116 and 120 cm H(2)O before E and E + ITL, respectively, and 110 and 114 cm H(2)O at 30 min postexercise). Whereas the amplitude of the diaphragm MEP was unaffected by E + ITL (+2.1 +/- 29.4%), a significant decrease was observed 10 min after E compared with baseline (-37.1 +/- 22.3%) and compared with E + ITL. The MEP amplitude of rectus femoris remained unchanged with E and E + ITL. The recruitment of synergistic agonists during E + ITL may have normalized the major ventilatory stress and reset up the excitability of the diaphragm pathway.

Functional imaging studies in normal humans have shown that the supplementary motor area (SMA) and the primary motor cortex (PMC) are coactivated during various breathing tasks. It is not known whether a direct pathway from the SMA to the diaphragm exists, and if so what properties it has. Using transcranial magnetic stimulation (TMS) a site at the vertex, representing the diaphragm primary motor cortex, has been identified. TMS mapping revealed a second area 3 cm anterior to the vertex overlying the SMA, which had a rapidly conducting pathway to the diaphragm (mean latency 16.7 ± 2.4 ms). In comparison to the vertex, the anterior position was characterized by a higher diaphragm motor threshold, a greater proportional increase in motor‐evoked potential (MEP) amplitude with voluntary facilitation and a shorter silent period. Stimulus–response curves did not differ significantly between the vertex and anterior positions. Using paired TMS, we also compared intracortical inhibition/facilitation (ICI/ICF) curves. In comparison to the vertex, the MEP elicited from the anterior position was not inhibited at short interstimulus intervals (1–5 ms) and was more facilitated at long interstimulus intervals (9–20 ms). The patterns of response were identical for the costal and crural diaphragms. We conclude that the two coil positions represent discrete areas that are likely to be the PMC and SMA, with the latter wielding a more excitatory effect on the diaphragm.

The effect of mechanical ventilation on the diaphragm motor cortex remains unknown. We assessed the effect of mechanical ventilation on diaphragm motor cortex excitability by measuring the costal and crural diaphragm motor-evoked potential (MEP) elicited by single and paired transcranial magnetic stimulation. In six healthy subjects, MEP recruitment curves of the costal and crural diaphragms were assessed at relaxed end expiration during spontaneous breathing [baseline tidal volume (Vt(baseline))] and isocapnic volume cycled ventilation delivered noninvasively (NIV) at three different levels of tidal volume (Vt(baseline), Vt(baseline) + 5 ml/kg liters, and Vt(baseline) + 10 ml/kg liters). The costal and crural diaphragm response to peripheral stimulation of the right phrenic nerve was not reduced by NIV. NIV reduced the costal and crural MEP amplitude during NIV (P < 0.0001) with the maximal reduction at Vt(baseline) + 5 ml/kg. Response to paired TMS showed that NIV (Vt(baseline) + 5 ml/kg) significantly increased the sensitivity of the cortical motoneurons to facilitatory (>9 ms) interstimulus intervals (P = 0.002), suggesting that the diaphragm MEP amplitude depression during NIV is related to neuromechanical inhibition at the level of motor cortex. Our results demonstrate that mechanical ventilation directly inhibits central projections to the diaphragm.

Patients with chronic obstructive pulmonary disease (COPD) face an increased respiratory load and in consequence have an elevated respiratory drive. We used transcranial magnetic stimulation (TMS) to investigate associated changes in corticospinal excitability both at rest and during voluntary facilitation at different levels of inspiratory effort. Diaphragm and abdominal motor thresholds were significantly lower in COPD than healthy controls, but the quadriceps response was the same. In patients there was a significant increase in diaphragm response from rest during 20% inspiratory efforts but no further increase with greater efforts. In controls there was a further stepwise increase at 40% and 60% of inspiratory effort. The cortical silent period was significantly shorter in COPD. Using paired stimulation to study intracortical inhibitory and excitatory circuits we found significantly less excitability of intracortical facilitatory circuits in patients at long (>7 ms) interstimulus intervals. These results suggest that there is a ceiling effect in motor control output to the respiratory muscles of patients with COPD.

This study aimed at determining whether twitch mouth pressure (TwPmo) induced by cervical magnetic stimulation (CMS) was sensitive to inspiratory muscle fatigue produced by whole body exercise (WBE) in normal subjects. Twenty subjects performed one or two of the following protocols: (i) cycling at 85% V̇O2,max until exhaustion; (ii) inspiratory resistive load (IRL) breathing at 62% of maximal inspiratory pressure until task failure. In eight subjects, oesophageal (TwPoes), gastric (TwPga) and transdiaphragmatic (TwPdi) pressures were recorded. The TwPmo was significantly reduced (P<0.05) 20 min after both WBE and IRL, from 17.5±4.4 to 15.9±3.9 cmH2O and from 19.4±4.9 to 17.7±4.5 cmH2O, respectively. Subsequently to IRL, the TwPdi decrease was associated with a reduction in TwPoes/TwPga ratio; not after WBE. Independently of the mode of ventilatory loading, inspiratory muscle fatigue was detected. Thus, inspiratory muscle fatigue after WBE can be assessed in normal subjects with a noninvasive technique.

A reliable submaximal test for assessing cardiorespiratory function would be of interest in clinical practice. Baba et al. (1996) proposed the oxygen uptake efficiency slope (OUES) derived from the relation between oxygen uptake (VO2 [ml (.) min(-1) (.) kg(-1)]) and minute ventilation (VE [L (.) min(-1)]) during incremental exercise. We evaluated the validity of OUES by comparing maximal oxygen uptake (VO2MAX) predicted from OUES to measured VO2max in 50 healthy males who performed a maximal treadmill test. They had widely differing physical fitness levels (VO2max range, 32.7 to 80.2 mlO(2) (.) min(-1) (.) kg(-1)). Predicted VO2MAX was not significantly different (p > 0.99) from measured VO2MAX (56.8 +/- 7.0 vs. 568 +/- 8.8 mlO(2) (.) min-1 (.) kg(-1)). The limits of agreement (Bland & Altman, 1986)were plus or minus 10.5 mlO(2) (.) min(-1) (.) kg(-1). Although OUES and VO2MAX were significantly correlated (r = 0.79), the wide interindividual variations in the difference between these two parameters may limit the usefulness of OUES in clinical practice.

The factors that may modulate ventilatory muscle fatigue during exercise are controversial. In this study the contribution of acidosis to exercise-induced diaphragmatic fatigue was investigated, using measurements of the twitch mouth pressure response (tw,Pmo) to cervical magnetic stimulation.After learning sessions, 14 healthy subjects performed two cycling tests (at 60% of maximal aerobic power for 16 min), one while breathing spontaneously (mean minute ventilation (V′e) 67.9 L·min−1) and the other while hypoventilating voluntarily (meanV′E53.8 L·min−1). Exercise was voluntarily set at a moderate power to avoid a fatiguing effect of exerciseper se.As compared with spontaneous breathing (SB), voluntary hypoventilation (VHV) significantly increased mean carbon dioxide tension in arterial blood (Pa,CO2) (51 mmHgversus41 mmHg) and significantly decreased arterial pH (7.28versus7.34). After 10 min of SB test, tw,Pmowas unchanged compared to the baseline value (19.1versus18.5 cmH2O) whereas tw,Pmofell significantly as compared to baseline (17.1versus18.5 cmH2O) and to SB (17.1versus19.1 cmH2O) after the VHV test.The results of this study suggest that exposure to hypercapnia may impair respiratory muscle function. This impairment could be more clinically relevant in patients with chronic obstructive lung disease.