EFFECTS OF OXYGEN BREATHING ON INSPIRATORY MUSCLE FATIGUE DURING RESISTIVE LOAD IN CYCLING MEN

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1 JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2009, 60, Suppl 5, M.O. SEGIZBAEVA, N.P. ALEKSANDROVA EFFECTS OF OXYGEN BREATHING ON INSPIRATORY MUSCLE FATIGUE DURING RESISTIVE LOAD IN CYCLING MEN Laboratory of Respiration Physiology, Pavlov Institute of Physiology, Russian Academy of Science, Saint-Petersburg, Russia The aim of the present study was to determine the development of the inspiratory muscle fatigue in healthy human during incremental cycling to exhaustion under mild and heavy resistive loaded breathing in air and oxygen. Minute ventilation, tidal volume, respiratory rate, inspiratory mouth pressure, and parasternal EMG activities were recorded during an incremental cycling test under mild (12 cmh 2 O l -1 s -1 ) and heavy (40 cmh 2 O l -1 s -1 ) resistive loading in air and oxygen in 8 men. The degree of inspiratory muscle fatigue was evaluated by analysis of the dynamics of inspiratory mouth pressure, 'tension-time' index, and the fall of the high-to-low (H/L) ratio of the parasternal EMG. It was found that oxygen breathing slowed the development of inspiratory muscles fatigue evoked by incremental cycling only during mild resistive loading, whereas hyperoxia had not influence on inspiratory muscle endurance during heavy resistive loading. Key words: incremental exercise, inspiratory muscle fatigue, oxygen, resistive loading, tidal volume INTRODUCTION Progressive loss of force with repeated muscle contractions, or fatigue, is an event which can be observed in all skeletal muscles (1, 2). Inspiratory muscles fatigue occurs in subjects with varying degrees of fitness level during exhaustive exercise (3, 4) or during resistive load (5, 6). It potentially exists in patients with chronic obstructive pulmonary diseases (COPD) and may possibility be a cause of respiratory failure. There is some evidence that ventilatory muscle fatigue could contribute to exercise limitation in normal humans and patients with COPD or obstructive sleep apnea (7, 8). Since the resistive load and/or exercise increase both diaphragmatic and intercostals muscle activity, either the rib cage muscles or diaphragm, or both may be fatigued, depending on the relative strengths of the muscles involved (9). The factors which result in fatigue are complex and probably interactive. These factors may be high inspiratory muscles workload (10), inadequacy of muscle blood and/or oxygen supply (11), arterial hypoxemia (12), or neurohormonal and metabolic modifications (13). The effect of O 2 on fatigue of respiratory muscles is of particular interest, because decrements in force-generating capacity in this system can result in respiratory failure and inadequate gas exchange. It has been reported that in hyperoxia whole-body exercise performance is improved compared with that in air (14) and resistance to fatigue increases during resistive loads at rest (5). Conversely, hypoxia induced by inspiration of 13% O 2 exacerbated inspiratory muscle fatigue as evidenced by decreased endurance time and earlier shifts in the electromyogram frequency spectrum (1, 15). These results suggest that inspiratory muscles are particularly sensitive to changes in blood oxygen when they contract under heavy mechanical loads. However, there has been an opinion that in healthy humans, fatigue of inspiratory muscles occurs by a mechanism that is insensitive to changes in blood O 2 content (16). The purpose of this study was to determine the possible role of inspired O 2 in the development of respiratory muscle fatigue in healthy humans. To answer this question, healthy trained men exercised to exhaustion with mild and heavy resistive loads during air or oxygen breathing. The experimental design was aimed at comparing the rate of the inspiratory muscle fatigue development under two exercise conditions, where inspired gas mixtures varied while maintaining work rate and resistive load at a similar level. Study subjects MATERIAL AND METHODS The study was approved by a local Ethics Committee and was performed in accordance with the ethical standards of the Helsinki Declaration for experimentation on human subjects. All subjects were familiarized with the experimental procedures and gave informed consent. Eight healthy, nonsmoking trained male subjects participated in the study. Their mean age was 23.2±1.8 yr, height ±2.9 cm, weight ±4.8 kg, and vital capacity - 4.8±0.6l. All of them had no history of cardiorespiratory diseases and had ventilatory functions within normal limits. Experimental protocol The subjects breathed quietly without resistive load for 10 min to allow familiarization to the breathing circuit. An external respiratory resistance was then added and maintained for 3 min.

2 112 Then, subjects exercised in the sitting position on an electronically braked cycle ergometer (Jaeger). An incremental cycling test was performed until exhaustion. The workload on the ergometer was increased by 30 W every 3 min until the subject was no longer able to maintain the pedaling frequency at a constant level (60 per min). All subjects were encouraged to exercise for as long as possible. The last workload for which the subject was able to complete the full minute of cycling was designated as W max. Each subject took part in four sessions, each performed on a different days in randomized order. In the first trial, subjects exercised with a mild resistive load (12 cmh 2 O l -1 s -1 ) and in the second one, with a heavy load (40 cmh 2 O l -1 s -1 ); inspiring room air or 100% oxygen (air or O 2 test). Subjects were unaware of the gas being inspired. The resistive load was created with metallic diaphragms having holes of different diameter, which were applied to inspiratory and expiratory channels of the breathing circuit. Ventilation and alveolar CO 2 Inspiratory flow (V I ) was measured with a pneumotachograph (Fleish No. 5), connected to the inspiratory port of a low-resistance Hans Rudolph valve. The V I signal was recorded, and inspiratory time (T I ), total breath cycle (T T ), duty cycle (T I /T T ), and respiratory frequency (f) were measured from this tracing. Tidal volume (V T ) was obtained by integration of the V I signal, and minute ventilation (V E ) was calculated from V T and f. The partial pressure of CO 2 (P ET CO 2 ) in the alveolar gas was measured at the mouth-peace from the peak end-tidal values recorded by a mass spectrometer MX 6203 (Russia). Mouth pressure Mouth pressure (P MI ) was measured at the mouthpiece via a pressure tap connected to a differential pressure transducer (PDP 1000 MD, Russia). The maximum mouth pressure (P MImax ) was measured for each subject during performance of a maximum inspiratory effort against an occluded airway at functional residual volume. The P MImax maneuvers were repeated until three reproducible measurements, sustained for >1 s, were recorded. The highest obtained value was used for the analysis. The level of power developed by all inspiratory muscles was assessed by the tension-time index TT m =P MI /P MImax T I /T T, where P MI is peak inspiratory mouth pressure, P MImax is the maximum mouth pressure, and T I /T T is the ratio of inspiratory time to breathing cycle time (duty cycle). Muscle activity measurements Electromyographic activity (EMG) was recorded from the parasternal intercostals muscles using surface electrodes. Electrodes were placed in the second and third intercostal spaces, just right off the sternal line. EMG signals were amplified and filtered with a band width of Hz. All recorded signals were monitored on-line and were stored on a computer IBM PC. Fourier analysis was performed using VU POINT program (ver. 1.27). High-frequency and low-frequency bands were taken to calculate the H/L ratio of parasternal muscles at Hz and Hz for H and L, respectively. The mean value of H/L for the first 10 breaths at the start of exercising was assigned a value of 100% and used as a control level. The subsequent recording was analyzed to determine whether H/L decreased. Data analysis All subjects performed each test 3 times and the trial with maximum work performance was taken for statistical analysis. All data are reported in absolute values as means ±SE. Student's t-test was used to detect differences between the mean values of normoxic vs. oxygen trials during mild and heavy resistive loads, respectively. The level of significance was set at P<0.05. RESULTS AND DISCUSSION Effect of air and oxygen breathing during mild resistive loading Table 1 demonstrates respiratory parameters in healthy humans at rest and incremental exercise with mild resistive loading (MRL) during room air and oxygen breathing. No significant alterations in tidal volume, frequency, minute Table 1. Ventilatory variables during rest and incremental exercise with MRL in room air and oxygen breathing. ROOM AIR Parameters Rest Workload+MRL (% of maximum) R 0 R W, Wt ± ± ± ±9* V E, l/min 8.9± ± ± ± ± ±1.3* V T, l 0.91± ± ± ± ± ±0.34 f, cycle/min 9.9± ± ± ± ± ±2.1 P ETCO2, mm Hg 32.7± ± ± ± ± ±3.1 P mi, cm H 2 O 1.1± ± ±1.2* 17.1±1.9* 33.4±2.3* 27.5±2.1 H/L, % ±15 77±11 68±14* OXYGEN W, Wt ±7 105±13 158±15 210±11* V E, l/min 9.5± ± ± ± ± ±1.2* V T, l 0.98± ± ± ± ± ±0.4 f, cycle/min 11.1± ± ± ± ± ±2.3 P ETCO2, mm Hg 31.7± ± ± ± ± ±2.9 P mi, cm H 2 O 1.0± ± ±1.8* 12.9±1.6* 18.1±2.1* 25.2±2.5 H/L, % ±11 86±12 81±9* Data are means±se; W, exercise workload; V E, minute ventilation; V T, tidal volume; f, breath frequency; P ET CO 2, end-tidal partial pressure; P MI, inspiratory mouth pressure; H/L, high-to-low frequency ratio of parasternal EMG. *Significant difference between air and oxygen breathing, P<0.05.

3 113 Fig. 1. Tidal volume (left scale; ) and peak inspiratory mouth pressure (right scale; ) during incremental exercise with mild resistive loading in air and oxygen breathing. Fig. 2. Tension-time index during incremental exercise with mild (A) and heavy resistive loading (B) in air ( ) and oxygen ( ) breathing. **Significant difference between air and oxygen breathing. Fig. 3. Tidal volume (left scale; ) and peak inspiratory mouth pressure (right scale; ) during incremental exercise with heavy resistive loading in air and oxygen breathing. ventilation and P ET CO 2 were observed at rest during oxygen breathing compared with air breathing. There was a tendency for decreases in V E and f and increases in V T and P ET CO 2 during mild resistive loaded compared with unloaded breathing both in air and O 2, but this trend was not significant. Maximum work performed by the subjects was significantly higher during mildloaded oxygen than air breathing (210±11 and 181±9 W, respectively; P<0.05). V E increased with exercise in both tests, reaching a maximum value at the end of exercise. The increase in lung ventilation was achieved by increases in f and V T in all subjects. However, an increment of V E was lower in O 2 than in air tests (P<0.05), despite of higher hypercapnic drive during oxygen breathing. P ET CO 2 rose to 56.7±3.1 mmhg in air breathing and to 61.5±2.9 mmhg in oxygen breathing. An increment in P MI induced by exercise was also significantly lower in hyperoxic than normoxic conditions. The decrease in V E and P MI increments might be related to a fall in hypoxic stimulation evoked by oxygen breathing. As shown in Fig.1, V T and peak value of P MI decreased in air (P<0.05), but not oxygen, breathing during the final minutes of exercise. The decrease in P MI is suggestive of the development of inspiratory muscles fatigue during exercise performed at loaded air breathing. This suggestion is strengthened by a calculation of the tension-time index and H/L ratio of parasternal muscles. The tension-time index of inspiratory muscles significantly rose in MRL during incremental exercise at room air breathing (Fig. 2A). It is known that an increase in the tension-time index above the threshold level indicates inspiratory muscle fatigue. During oxygen breathing, the tension-time index did not rise above the

4 114 Table 2. Ventilatory variables during rest and incremental exercise with HRL in room air and oxygen breathing. ROOM AIR Parameters Rest Workload+HRL (% of maximum) R 0 R W, Wt ± ± ± ±9.1 V E, l/min 9.1± ± ± ± ± ±0.9 V T, l 0.82± ± ± ± ± ±0.21 f, cycle/min 9.9± ± ± ± ± ±1.9 P ETCO2, mm Hg 31.1± ± ± ± ± ±3.5 P mi, cm H 2 O 0.9± ± ± ± ± ±4.6 H/L, % ±14 67±13 61±13 OXYGEN W, Wt ± ± ± ±11.0 V E, l/min 9.8± ± ± ± ± ±1.1 V T, l 0.84± ± ± ± ± ±0.19 f, cycle/min 11.9± ± ± ± ± ±2.3 P ETCO2, mm Hg 30.9± ± ± ± ± ±3.9 P mi, cm H 2 O 1.0± ± ± ± ± ±2.4 H/L, % ±12 69±12 63±11 Data are means ±SE; W, exercise workload; V E, minute ventilation; V T, tidal volume; f, breath frequency; P ET CO 2, end-tidal partial pressure; PMI, inspiratory mouth pressure ; H/L, high-to-low frequency ratio of parasternal EMG. The differences between air and oxygen breathing were insignificant. fatigue threshold level. Further evidence of inspiratory muscle fatigue during exercise in air was a fall in the H/L ratio of the parasternal EMG toward the exercise end. Such a change in EMG power spectrum predicts the development of inspiratory muscle fatigue (17, 18). The H/L ratio was decreased by 32% during air breathing, but only 19% during oxygen breathing. Thus, the data obtained in the present study suggest that incremental exercise with mild resistive loading evokes the development of inspiratory muscles fatigue in air breathing. On the other hand, oxygen breathing slows the appearance of inspiratory muscles fatigue. The improved exercise performance in O 2 is associated with a delay in H/L fall, the absence of a decrease in peak P MI, and an increase in the tension-time index. These results are in agreement with those previously observed during resistive loading at rest (5, 6) and during exercise with unloaded breathing (14). In those previous studies, positive effects of hyperoxia on diaphragm function and exercise performance have also been found. Effect of air and oxygen breathing during heavy resistive loading The mean values of respiratory parameters during incremental exercise with heavy resistive loading (HRL) in air and oxygen breathing are presented in Table 2. At rest, HRL did not induce significant changes in the level of ventilation, respiratory rate, tidal volume, and P ET CO 2. However, the maintenance of a constant level of V E was due to a significant increase in inspiratory pressure. Peak value of P MI rose more than 700% of the control level (unloaded breathing). There were no differences in the value of maximum work performed by the subjects between air and oxygen breathing; 135±9 and 139±11 W, respectively. V E increased with exercise and its increment was alike same in both tests. P ET CO 2 rose to 64.6±3.5 mmhg during exercise in air and to 65.8±3.9 mm Hg in oxygen. Moreover, the dynamics of changes P MI and V T during incremental exercise in air and oxygen also were alike (Fig. 3); during the final minutes of cycling the values of P MI and V T decreased. The tension-time index of inspiratory muscles rose above the fatigue threshold level during exercise in both air and oxygen (Fig. 2B). The H/L ratio of the parasternal EMG decreased at the end of exercise by 39% in air and 37% in oxygen breathing. The data of the present study suggest that hyperoxia has not positive effect on inspiratory muscle function in exercise with heavy resistive loading. In this condition, inspiratory muscle fatigue develops with equal rate during exercise in both air and oxygen. One of the possible explanations of such results may be very high values of P MI and tension-time index in heavy resistive load in both tests. It is known that factors leading to respiratory muscle fatigue during exercise include increased work by respiratory muscles and reduced blood flow/oxygen availability (11). It is supposed that in forced hyperventilation the arterial supply to the inspiratory muscles is impaired due to occlusion of intramuscular vessels during intense muscular contractions and a shortening of the relaxation time of respiratory muscles in the expiratory phase (19). In conclusion, the present study demonstrates that inspiratory muscle fatigue occurs in healthy subjects during high-intensity exercise with inspiratory resistive loading. Oxygen breathing increases work performance and slows the development the inspiratory muscles fatigue evoked by incremental cycling during mild resistive loading, but fails to do so during heavy loads. Conflict of interests: None declared. REFERENCES 1. Jardim J, Farkas G, Prefault C, Thomas D, Macklem PT, Roussos C. 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