Diaphragmatic Fatigue Research Articles

Corrigendum

CORRIGENDUMCorrigendumPublished Online:01 Oct 2010https://doi.org/10.1152/japplphysiol.zdg-9260-corr.2010Original articleMoreSectionsPDF (34 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Vol. 109, August 2010Taylor BJ, West CR, Romer LM. No effect of arm-crank exercise on diaphragmatic fatigue or ventilatory constraint in Paralympic athletes with cervical spinal cord injury. J Appl Physiol 109: , 2010. First published May 20, 2010; doi:10.1152/japplphysiol.00227.2010.—The flow and volume axes in Figure 4 were incorrect; consequently, the derived variables came out much lower than the actual values in Table 2. The corrected figure and legend appear below.Fig. 4.Group mean ensemble average tracings of tidal flow-volume loops plotted within the largest maximal flow-volume loop obtained at baseline (solid line) and <2 min after exercise (dashed line). Note that despite limited evidence of expiratory flow limitation, EELV and EILV increased early during exercise and remained elevated through to the final minute of exercise.Download figureDownload PowerPointThis article has no references to display. Download PDF Previous Back to Top FiguresReferencesRelatedInformationRelated ArticlesNo effect of arm-crank exercise on diaphragmatic fatigue or ventilatory constraint in Paralympic athletes with cervical spinal cord injury 01 Aug 2010Journal of Applied Physiology More from this issue > Volume 109Issue 4October 2010Pages 1285-1285 Copyright & PermissionsCopyright © 2010 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.zdg-9260-corr.2010History Published online 1 October 2010 Published in print 1 October 2010 Metrics

Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

BackgroundGreater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.MethodsTwelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO2 = 80%) and hyperoxic (FiO2 = 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (Pdi,tw ) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (Pga,tw ) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.ResultsHypoxia enhanced hyperpnoea-induced Pdi,tw and Pga,tw reductions both immediately after hyperpnoea (Pdi,tw : normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; Pga,tw : normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all P < 0.05) and after 30 min of recovery (Pdi,tw : normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; Pga,tw : normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all P < 0.05). No significant difference in Pdi,tw or Pga,tw reductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.ConclusionsThese results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O2 transport as during exercise in altitude or in hypoxemic patients.

No effect of arm-crank exercise on diaphragmatic fatigue or ventilatory constraint in Paralympic athletes with cervical spinal cord injury

Cervical spinal cord injury (CSCI) results in a decrease in the capacity of the lungs and chest wall for pressure, volume, and airflow generation. We asked whether such impairments might increase the potential for exercise-induced diaphragmatic fatigue and mechanical ventilatory constraint in this population. Seven Paralympic wheelchair rugby players (mean + or - SD peak oxygen uptake = 16.9 + or - 4.9 ml x kg(-1) x min(-1)) with traumatic CSCI (C(5)-C(7)) performed arm-crank exercise to the limit of tolerance at 90% of their predetermined peak work rate. Diaphragm function was assessed before and 15 and 30 min after exercise by measuring the twitch transdiaphragmatic pressure (P(di,tw)) response to bilateral anterolateral magnetic stimulation of the phrenic nerves. Ventilatory constraint was assessed by measuring the tidal flow volume responses to exercise in relation to the maximal flow volume envelope. P(di,tw) was not different from baseline at any time after exercise (unpotentiated P(di,tw) = 19.3 + or - 5.6 cmH(2)O at baseline, 19.8 + or - 5.0 cmH(2)O at 15 min after exercise, and 19.4 + or - 5.7 cmH(2)O at 30 min after exercise; P = 0.16). During exercise, there was a sudden, sustained rise in operating lung volumes and an eightfold increase in the work of breathing. However, only two subjects showed expiratory flow limitation, and there was substantial capacity to increase both flow and volume (<50% of maximal breathing reserve). In conclusion, highly trained athletes with CSCI do not develop exercise-induced diaphragmatic fatigue and rarely reach mechanical ventilatory constraint.

Diaphragmatic fatigue is counterbalanced during exhaustive long-term exercise

Based on externally paced (repetitive) short-term trials exercise-induced diaphragmatic fatigue has been shown to manifest after rather than during exercise. The current study aimed at investigating diaphragmatic contractility and diaphragmatic fatigue during self-paced long-term exhaustive exercise at maximally tolerated loading by the use of supramaximal twitch transdiaphragmatic pressure (TwPdi). Seven trained subjects (VO(2max) 63.3+/-13.9 ml kg(-1) min(-1)) performed self-paced long-term exhaustive exercise at maximally tolerated loading (45 min+endspurt, initial workload 85% VO(2max)) followed by recovery (9 min). TwPdi (every 45 s) and ergospirometric data (continuously) were assessed throughout the protocol. Diaphragmatic contractility tended to initially increase during the exercise protocol with a slight decline and final increase during endspurt. Diaphragmatic fatigue manifested only after exercise termination (TwPdi rest 2.6+/-0.8 kPa; TwPdi exercise start/mid/end 2.9+/-0.7 kPa vs. 2.6+/-0.8 kPa vs. 2.4+/-0.6 kPa; TwPdi endspurt/recovery 2.7+/-0.8 kPa vs. 1.9+/-0.6 kPa). In conclusion, diaphragmatic contractility tends to decrease but manifestation of diaphragmatic fatigue is counterbalanced during self-paced long-term exhaustive exercise at maximally tolerated loading.

Sex differences in exercise-induced diaphragmatic fatigue in endurance-trained athletes

There is evidence that female athletes may be more susceptible to exercise-induced arterial hypoxemia and expiratory flow limitation and have greater increases in operational lung volumes during exercise relative to men. These pulmonary limitations may ultimately lead to greater levels of diaphragmatic fatigue in women. Accordingly, the purpose of this study was to determine whether there are sex differences in the prevalence and severity of exercise-induced diaphragmatic fatigue in 38 healthy endurance-trained men (n = 19; maximal aerobic capacity = 64.0 +/- 1.9 ml x kg(-1) x min(-1)) and women (n = 19; maximal aerobic capacity = 57.1 +/- 1.5 ml x kg(-1) x min(-1)). Transdiaphragmatic pressure (Pdi) was calculated as the difference between gastric and esophageal pressures. Inspiratory pressure-time products of the diaphragm and esophagus were calculated as the product of breathing frequency and the Pdi and esophageal pressure time integrals, respectively. Cervical magnetic stimulation was used to measure potentiated Pdi twitches (Pdi,tw) before and 10, 30, and 60 min after a constant-load cycling test performed at 90% of peak work rate until exhaustion. Diaphragm fatigue was considered present if there was a >or=15% reduction in Pdi,tw after exercise. Diaphragm fatigue occurred in 11 of 19 men (58%) and 8 of 19 women (42%). The percent drop in Pdi,tw at 10, 30, and 60 min after exercise in men (n = 11) was 30.6 +/- 2.3, 20.7 +/- 3.2, and 13.3 +/- 4.5%, respectively, whereas results in women (n = 8) were 21.0 +/- 2.1, 11.6 +/- 2.9, and 9.7 +/- 4.2%, respectively, with sex differences occurring at 10 and 30 min (P < 0.05). Men continued to have a reduced contribution of the diaphragm to total inspiratory force output (pressure-time product of the diaphragm/pressure-time product of the esophagus) during exercise, whereas diaphragmatic contribution in women changed very little over time. The findings from this study point to a female diaphragm that is more resistant to fatigue relative to their male counterparts.

Diaphragmatic fatigue under inspiratory resistive load in healthy subjects and the effect of several selections of frequency bands on the H/L (high/low) ratio

In seven normal adult males the authors studied diaphragmatic fatigue by analysis of the power spectrum of the diaphragmatic electromyogram obtained with an esophageal electrode, and of the change of transdiaphragmatic pressure. Diaphragmatic fatigue was produced by inspiring through a resistive load, and mean value of the index of the tension time of the diaphragm (TTdi) maintained until fatigue was 0.33 +/- 0.09, which has been known to produce fatigue. The mean value of ratios of power at high frequencies to power at low frequencies (H/L) decreased to 61.2 +/- 16.8% of the initial value at just before breaking time. Breaking time was 4.88 +/- 1.37 minutes in average. The selection of low and high band widths for analysis of H/L ratio has differed slightly in the literature, but such differences do not have any substantial influence on the estimation of the changes of H/L ratio.

Dyspnea and ventilatory muscle function during exercise on air and oxygen breathing in patients with chronic obstructive pulmonary disease (COPD)

Exercise performance and dyspnea in COPD patients have been shown to be improved with supplemental oxygen, although the exact mechanisms resulting in the improvement are still unclear. The purpose of the present study was to investigate a possible relationship between ventilatory muscle function and sensation of dyspnea (modified Borg Scale) during exercise on 20% O2 and 30% O2. Eight patients with COPD (FEV1 1.06 L +/- 0.30 L) exercised on a treadmill two times breathing compressed air or 30% oxygen with a one hour rest in between. The electrical activity of the diaphragm (EMGdi) was recorded with esophageal electrodes, and that of the sternomastoid muscle (EMGsm) was recorded from the fine wire electrodes. The ratio of high frequency (150 to 350 Hz) to low frequency (20 to 47 Hz) power (H/L) of EMGdi was analyzed to assess diaphragmatic fatigue, which was defined as a 20% fall of H/L ratio from the control value. Flow, volume, O2 Saturation (SaO2), esophageal pressure (Pes) and transdiaphragmatic pressure (Pdi) were measured. Tension time index (TTdi) was calculated from Pdi and the ratio of inspiratory time to total time for one cycle (Ti/Ttot). At rest, we measured maximal esophageal pressure (Pesmax), maximal transdiaphragmatic pressure (Pdimax), maximal integrated EMGdi (EMGdimax) and EMGsm (EMGsmmax). Incremental exercise was discontinued by dyspnea. The walking distance achieved was increased in all patients on 30% O2. Dyspnea and desaturation were significantly improved on 30% O2 breathing, and the onset of diaphragmatic fatigue was delayed.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal muscle fatigue following exercise in chronic obstructive pulmonary disease

BackgroundIn patients with chronic obstructive pulmonary disease, a restriction on maximum ventilatory capacity contributes to exercise limitation. It has been demonstrated that the diaphragm in COPD is relatively protected from fatigue during exercise. Because of expiratory flow limitation the abdominal muscles are activated early during exercise in COPD. This adds significantly to the work of breathing and may therefore contribute to exercise limitation. In healthy subjects, prior expiratory muscle fatigue has been shown itself to contribute to the development of quadriceps fatigue. It is not known whether fatigue of the abdominal muscles occurs during exercise in COPD.MethodsTwitch gastric pressure (TwT10Pga), elicited by magnetic stimulation over the 10th thoracic vertebra and twitch transdiaphragmatic pressure (TwPdi), elicited by bilateral anterolateral magnetic phrenic nerve stimulation were measured before and after symptom-limited, incremental cycle ergometry in patients with COPD.ResultsTwenty-three COPD patients, with a mean (SD) FEV1 40.8(23.1)% predicted, achieved a mean peak workload of 53.5(15.9) W. Following exercise, TwT10Pga fell from 51.3(27.1) cmH2O to 47.4(25.2) cmH2O (p = 0.011). TwPdi did not change significantly; pre 17.0(6.4) cmH2O post 17.5(5.9) cmH2O (p = 0.7). Fatiguers, defined as having a fall TwT10Pga ≥ 10% had significantly worse lung gas transfer, but did not differ in other exercise parameters.ConclusionsIn patients with COPD, abdominal muscle but not diaphragm fatigue develops following symptom limited incremental cycle ergometry. Further work is needed to establish whether abdominal muscle fatigue is relevant to exercise limitation in COPD, perhaps indirectly through an effect on quadriceps fatigability.

Reply: Combined 18F-FDG and Fluoride Approach in PET/CT Imaging: Is There a Clinical Future?

Transdiaphragmatic (Pdi) and oesophageal pressures (Pes) are useful in understanding the pathophysiology of the respiratory system. They provide insight into respiratory drive, intrinsic positive end-expiratory pressure, diaphragmatic fatigue and weaning failure. <h3>Background</h3> The use of Pdi and Pes in clinical practice is restricted due to the invasiveness of the technique and the cumbersome equipment needed. On the other hand, diaphragmatic displacement is non-invasively and easily assessed with M-mode ultrasound. <h3>Purpose</h3> We observed striking similarities in shape and magnitude between M-mode diaphragmatic displacement, Pes and Pdi pressures. The study aimed to evaluate if the information provided by these two pressures could be obtained non-invasively from the diaphragmatic displacement curve. <h3>Material and methods</h3> In 14 consecutive intubated patients undergoing a weaning trial, simultaneous recordings of Pes and Pdi pressures and the diaphragmatic displacement were assessed while breathing spontaneously and during a sniff-like manoeuvre. Moreover, the slope of the diaphragmatic displacement curve during relaxation was compared with the maximal relaxation rate (MRR) obtained from the Pdi curve. <h3>Results</h3> More than 200 breaths were analysed in pairs. Diaphragmatic displacement significantly correlated with Pdi (R²=0.33, p&lt;0.001) and Pes (R²=0.44, p&lt;0.001), and this correlation further improved during sniff (R²=0.47, p&lt;0.001) and (R²=0.64, p&lt;0.001), respectively. Additionally, a significant correlation was found between the relaxation slope derived from the diaphragmatic displacement curve and the MRR derived from the Pdi curve, both in normal breathing (R²=0.379, p&lt;0.001) and during the sniff manoeuvre (R²=0.71, p&lt;0.001). <h3>Conclusions</h3> M-mode diaphragmatic displacement parameters correlate well with the ones obtained from oesophageal pressure and Pdi, particularly during sniffing. Diaphragmatic displacement assessment possibly offers an alternative non-invasive solution for understanding and clinically monitoring the diaphragmatic contractile properties and weaning failure due to diaphragmatic fatigue.

Infection decreases fatty acid oxidation and nuclear hormone receptors in the diaphragm

Respiratory failure is a major cause of mortality during septic shock and is due in part to decreased ventilatory muscle contraction. Ventilatory muscles have high energy demands; fatty acid (FA) oxidation is an important source of ATP. FA oxidation is regulated by nuclear hormone receptors; studies have shown that the expression of these receptors is decreased in liver, heart, and kidney during sepsis. Here, we demonstrate that lipopolysaccharide (LPS) decreases FA oxidation and the expression of lipoprotein lipase (LPL), FA transport protein 1 (FATP-1), CD36, carnitine palmitoyltransferase beta, medium chain acyl-CoA dehydrogenase (MCAD), and acyl-CoA synthetase, key proteins required for FA uptake and oxidation, in the diaphragm. LPS also decreased mRNA levels of PPARalpha and beta/delta, RXRalpha, beta, and gamma, thyroid hormone receptor alpha and beta, and estrogen related receptor alpha (ERRalpha) and their coactivators PGC-1alpha, PGC-1beta, SRC1, SRC2, Lipin 1, and CBP. Zymosan resulted in similar changes in the diaphragm. Finally, in PPARalpha deficient mice, baseline CPT-1beta and FATP-1 levels were markedly decreased and were not further reduced by LPS suggesting that a decrease in the PPARalpha signaling pathway plays an important role in inducing some of these changes. The decrease in FA oxidation in the diaphragm may be detrimental, leading to decreased diaphragm contraction and an increased risk of respiratory failure during sepsis.

Influence of Respiratory Muscle Blood Flow and Hypoxemia on Exercise Induced Diaphragmatic Fatigue in Humans

Influence of Respiratory Muscle Blood Flow and Hypoxemia on Exercise Induced Diaphragmatic Fatigue in Humans

Hyperinflation-induced cardiorespiratory failure in rats

We previously showed that severe inspiratory resistive loads cause acute (<1 h) cardiorespiratory failure characterized by arterial hypotension, multifocal myocardial infarcts, and diaphragmatic fatigue. The mechanisms responsible for cardiovascular failure are unknown, but one factor may be the increased ventricular afterload caused by the large negative intrathoracic pressures generated when breathing against an inspiratory load. Because expiratory threshold loads increase intrathoracic pressure and decrease left ventricular afterload, we hypothesized that anesthetized rats forced to breathe against such a load would experience only diaphragmatic failure. Loading approximately doubled end-expiratory lung volume, halved respiratory frequency, and caused arterial hypoxemia and hypercapnia, respiratory acidosis, and increased inspiratory drive. Although hyperinflation immediately reduced the diaphragm's mechanical advantage, fatigue did not occur until near load termination. Mean arterial pressure progressively fell, becoming significant (cardiovascular failure) midway through loading despite tachycardia. Loading was terminated (endurance 125 +/- 43 min; range 82-206 min) when mean arterial pressure dropped below 50 mmHg. Blood samples taken immediately after load termination revealed hypoglycemia, hyperkalemia, and cardiac troponin T, the last indicating myocardial injury that was, according to histology, mainly in the right ventricle. This damage probably reflects a combination of decreased O(2) delivery (decreased venous return and arterial hypoxemia) and greater afterload due to hyperinflation-induced increase in pulmonary vascular resistance. Thus, in rats breathing at an increased end-expiratory lung volume, cardiorespiratory, not just respiratory, failure still occurred. Right heart injury and dysfunction may contribute to the increased morbidity and mortality associated with acute exacerbations of obstructive airway disease.

Effect of expiratory resistive loading on inspiratory and expiratory muscle fatigue

Inspiratory and expiratory pressures are increased during expiratory resistive loading (ERL). We asked whether ERL elicits inspiratory as well as expiratory muscle fatigue. On four separate days, seven male subjects underwent ERL to task failure. Subjects maintained respiratory frequency at 15 breaths min(-1), expiratory gastric pressure at 40% or 60% of maximum, and expiratory duty cycle at 0.4 or 0.7 (ERL(40%0.4), ERL(40%0.7), ERL(60%0.4), ERL(60%0.7)). Inspiratory and abdominal muscle contractility was assessed before and up to 30 min after ERL by measuring transdiaphragmatic twitch pressure (P(di,tw)) and gastric twitch pressure (P(ga,tw)) in response to magnetic nerve stimulation. After each trial, P(di,tw) and P(ga,tw) were reduced below baseline values (-9 to -15% for P(di,tw) and -15 to -22% for P(ga,tw); P<0.05). The severity of diaphragm fatigue was unaffected by expiratory pressure production or expiratory duty cycle, whereas extending the expiratory duty cycle increased the severity of abdominal muscle fatigue. In conclusion, ERL elicits contractile fatigue of the diaphragm and the abdominal muscles.

Biphasic Effects of FKBP12 on RyR1 Activity

The skeletal muscle Ca2+ release channel (RyR1) binds four molecules of the immunophilin FKBP12 (FK506 Binding Protein, 12kDa). The interaction of FKBP12 with RyR1 is thought to both stabilize a closed state of the channel and promote cooperative interactions among its four subunits. We find that a (80-90%) decrease in FKBP12 concentration in skeletal muscle slows diaphragm fatigue compared to wild-type diaphragms, but this fatigue resistance is lost if the muscle is treated with rapamycin, suggesting that the slowing of fatigue requires some bound FKBP, but is reversed by higher FKBP12 concentrations. Myotubes from FKBP12 deficient mice display smaller voltage gated Ca2+ transients and smaller fractional decreases in the transients with repetitive stimulation than wild-type or Cre+ myotubes. Treatment of myotubes from the FKBP12 deficient mice with rapamycin further decreases the Ca2+ transients. Over-expression of FKBP12 also decreases the Ca2+ transient. These findings suggest that FKBP12 has a biphasic effect on RyR1 activity: some FKBP12 is required for maximal voltage gated Ca2+ release, but full saturation of RyR1 sites decreases voltage gated release. This work was supported by grants from NIH (AR041802) and MDA to S.L.H.

Determinants of weaning success in patients with prolonged mechanical ventilation

IntroductionPhysiological determinants of weaning success and failure are usually studied in ventilator-supported patients, comparing those who failed a trial of spontaneous breathing with those who tolerated such a trial and were successfully extubated. A major limitation of these studies was that the two groups may be not comparable concerning the severity of the underlying disease and the presence of comorbidities. In this physiological study, we assessed the determinants of weaning success in patients acting as their own control, once they are eventually liberated from the ventilator.MethodsIn 30 stable tracheotomised ventilator-dependent patients admitted to a weaning center inside a respiratory intensive care unit, we recorded the breathing pattern, respiratory mechanics, inspiratory muscle function, and tension-time index of diaphragm (TTdi = Pdisw/Pdimax [that is, tidal transdiaphragmatic pressure over maximum transdiaphragmatic pressure] × Ti/Ttot [that is, the inspiratory time over the total breath duration]) at the time of weaning failure (T0). The measurements were repeated in all the patients (T1) either during a successful weaning trial (successful weaning [SW] group, n = 16) or 5 weeks later, in the case of repeated weaning failure (failed weaning [FW] group, n = 14).ResultsCompared to T0, in the FW group at T1, significant differences were observed only for a reduction in spontaneous breathing frequency and in TTdi (0.21 ± 0.122 versus 0.14 ± 0.054, P = 0.008). SW patients showed a significant increase in Pdimax (34.9 ± 18.9 cm H2O versus 43.0 ± 20.0, P = 0.02) and decrease in Pdisw/Pdimax (36.0% ± 15.8% versus 23.1% ± 7.9%, P = 0.004).ConclusionsThe recovery of an inadequate inspiratory muscle force could be the major determinant of 'late' weaning success, since this allows the patients to breathe far below the diaphragm fatigue threshold.

Contribution of respiratory muscle blood flow to exercise‐induced diaphragmatic fatigue in trained cyclists

We investigated whether the greater degree of exercise-induced diaphragmatic fatigue previously reported in highly trained athletes in hypoxia (compared with normoxia) could have a contribution from limited respiratory muscle blood flow. Seven trained cyclists completed three constant load 5 min exercise tests at inspired O(2) fractions (FIO2) of 0.13, 0.21 and 1.00 in balanced order. Work rates were selected to produce the same tidal volume, breathing frequency and respiratory muscle load at each FIO2 (63 +/- 1, 78 +/- 1 and 87 +/- 1% of normoxic maximal work rate, respectively). Intercostals and quadriceps muscle blood flow (IMBF and QMBF, respectively) were measured by near-infrared spectroscopy over the left 7th intercostal space and the left vastus lateralis muscle, respectively, using indocyanine green dye. The mean pressure time product of the diaphragm and the work of breathing did not differ across the three exercise tests. After hypoxic exercise, twitch transdiaphragmatic pressure fell by 33.3 +/- 4.8%, significantly (P < 0.05) more than after both normoxic (25.6 +/- 3.5% reduction) and hyperoxic (26.6 +/- 3.3% reduction) exercise, confirming greater fatigue in hypoxia. Despite lower leg power output in hypoxia, neither cardiac output nor QMBF (27.6 +/- 1.2 l min(-1) and 100.4 +/- 8.7 ml (100 ml)(-1) min(-1), respectively) were significantly different compared with normoxia (28.4 +/- 1.9 l min(-1) and 94.4 +/- 5.2 ml (100 ml)(-1) min(-1), respectively) and hyperoxia (27.8 +/- 1.6 l min(-1) and 95.1 +/- 7.8 ml (100 ml)(-1) min(-1), respectively). Neither IMBF was different across hypoxia, normoxia and hyperoxia (53.6 +/- 8.5, 49.9 +/- 5.9 and 52.9 +/- 5.9 ml (100 ml)(-1) min(-1), respectively). We conclude that when respiratory muscle energy requirement is not different between normoxia and hypoxia, diaphragmatic fatigue is greater in hypoxia as intercostal muscle blood flow is not increased (compared with normoxia) to compensate for the reduction in PaO2, thus further compromising O(2) supply to the respiratory muscles.

Post-exercise diaphragm shielding: A novel approach to exercise-induced diaphragmatic fatigue

Based on the "post-exercise diaphragm shielding" hypothesis this study tested whether both diaphragmatic force-generation (DFG) and diaphragmatic fatigue (DF) remain unchanged during consecutive exercise-trials. Twelve subjects (V(O2 max) 58.4+/-6.6 ml kg(-1) min(-1)) performed three consecutive exercise-trials (T(alpha)/T(beta)/T(gamma); workload(max) 85% V(O2 max)) each followed by recovery (6 min). Twitch transdiaphragmatic pressure during supramaximal magnetic phrenic nerve stimulation (TwPdi, every 30s), ratings of perceived exertion (RPE, every 90 s) and ergospirometric data (continuously) were assessed throughout the entire protocol (46.5 min). DFG and DF did not differ among all trials (TwPdi-baseline: 2.2+/-0.7 kPa; TwPdi-peak: T(alpha)/T(beta)/T(gamma) 3.1+/-0.7 kPa vs 3.0+/-0.8 kPa vs 3.2+/-0.8 kPa; TwPdi-bottom: T(alpha)/T(beta)/T(gamma) 1.9+/-0.6 kPa vs 2.0+/-0.7 kPa vs 1.8+/-0.5 kPa, both p>0.4, RM-ANOVA). Furthermore, TwPdi revealed close relationships with RPE (r=0.91, p<0.0001) and oxygen uptake (r=0.94, p<0.0001) during exercise. In conclusion, both DFG (baseline-to-peak) and DF (baseline-to-bottom) achieve similar magnitudes during and after consecutive exercise-trials and are closely linked to RPE and oxygen uptake. This suggests that DF neither reflects impaired diaphragmatic function nor impairs exercise performance; rather it is likely to reflect post-exercise diaphragm shielding.

The Effects of N-Acetylcysteine on Respiratory Muscle Fatigue During Heavy Exercise

Diaphragmatic fatigue is known to limit endurance performance during heavy exercise. Previous reports have shown that diaphragmatic fatigue is reduced in rats with N-acetylcysteine (NAC; a nonspecific antioxidant) infusion suggesting that oxidative stress contributes to this fatigue. However, it is not know if oral supplementation of NAC will reduce respiratory muscle fatigue during heavy exercise in humans. PURPOSE: To determine the effect of an acute oral dose of NAC on respiratory muscle fatigue during whole body heavy exercise. METHODS: Eight healthy men (22+2 yrs; VO2peak: 43+5 ml/kg/min) initially completed baseline pulmonary function tests followed by an incremental cycle VO2peak test. Subjects then performed a randomized, double blind crossover study where subjects were given either placebo (PLA) or NAC (1800 mg) 45 min prior to a constant load (85% VO2peak), discontinuous, 30 minute cycle exercise test. Tests were separated by one week. Maximum pressures (inspiratory, PImax; expiratory, PEmax) and venous blood samples (lactate and total glutathione) were made prior to- and following each 5-min of exercise. RESULTS: There was no difference (p>0.05) in PImax between NAC (127.9+34.1 cmH2O) or PLA (134.1+28.1 cmH2O) at rest. During exercise, PImax was significantly lower (~14%) in 6 of 8 subjects with PLA compared to NAC at minutes 25 and 30; whereas with NAC, PImax did not change (p>0.05) from rest throughout exercise indicating no respiratory muscle fatigue. There was no difference (p>0.05) in PEmax, plasma glutathione, lactate, VO2, VE, or HR between PLA and NAC at rest or during exercise. CONCLUSIONS: These results suggest that an acute dose of NAC reduces respiratory muscle fatigue during high intensity exercise but does not alter other ventilatory or metabolic indices. These data indicate that NAC's affect on respiratory muscles may favorably influence endurance exercise performance. Support from Kansas State University Research Grant

Commentaries on Viewpoint: Fatigue mechanisms determining exercise performance: Integrative physiology is systems physiology

Commentaries on Viewpoint: Fatigue mechanisms determining exercise performance: Integrative physiology is systems physiology

Effect of Endurance Training on the Oxidative Capacity of Skeletal Muscle in Emphysema Hamster Model

Emphysema is a debilitating disease that is characterized by irreversible damage in the alveolar walls due to lung hyperinflation. One of the major consequences of this disease is diminished exercise capacity, thought to be caused by blood-gas imbalances, or from peripheral mechanisms such as reductions in skeletal muscle blood flow, or alterations in metabolism. PURPOSE: The purpose of this research was to determine the effects of endurance exercise training on the oxidative capacity of skeletal muscle in the elastase-induced emphysema hamster model. METHODS: Thirty-five adult male hamsters were utilized for this study. The hamsters were randomly divided by disease state; emphysema (EMP) or none (noEMP); activity level, endurance exercised trained (Ex), or sedentary (Sed); and dobutamine timing, prevention of diaphragm fatigue before simulated exercise stress (Prev), or treatments of diaphragm fatigue after simulated exercise (Tx). Cytochrome oxidase levels in the vastus lateralis, gastrocnemius, and soleus were analyzed. Group comparisons were made using an ANOVA. RESULTS: The emphysemic endurance trained hamsters showed significantly higher oxidative capacities (measured via μmol/min/g) in the vastus lateralis (Ex/EMP: 6.24 ± 2.68 vs. Sed/EMP: 3.56± 2.41, p<0.05). The endurance trained hamsters showed significantly higher oxidative capacities in both the treatment and prevention mechanisms of dobutamine administration in the vastus lateralis (Ex/Tx: 6.54 ± 2.30 vs. Sed/Tx: 4.34 ± 3.08 and, Ex/Prev: 5.45 ± 2.69 vs. Sed/Prev: 2.88 ± 1.55, p<0.05) and the soleus (Ex/Tx: 6.57 ± 2.92 vs. Sed/Tx: 6.09 ± 2.51 and, Ex/Prev: 5.83 ± 2.49 vs. Sed/Prev: 3.03 ± 0.68, p<0.05) when compared to those sedentary hamsters. However the hamsters that were sedentary were more responsive to the dobutamine treatment when compared to the dobutamine prevention in the vastus lateralis and soleus. CONCLUSION: Endurance training decreased the loss of oxidative capacity in hamster skeletal muscle that occurs with emphysema.