Attenuated inspiratory muscle metaboreflex in endurance-trained individuals

The inspiratory metaboreflex is activated during loaded breathing to task failure and induces sympathetic activation and peripheral vasoconstriction that may limit exercise performance. Inspiratory muscle training appears to attenuate the inspiratory metaboreflex in healthy subjects. Since whole body aerobic exercise training improves breathing endurance and inspiratory muscle strength, we hypothesized that endurance-trained individuals would demonstrate a blunted inspiratory muscle metaboreflex in comparison to sedentary individuals. We studied 9 runners (23±0.7 years; maximal oxygen uptake [VO2 max] = 53 ± 4 ml kg(-1) min(-1)) and 9 sedentary healthy volunteers (24±0.7 years; VO2 max = 37 ±2 ml kg(-1) min(-1)). The inspiratory muscle metaboreflex was induced by breathing against an inspiratory load of 60% of maximal inspiratory pressure (MIP), with prolonged duty cycle. Arterial pressure, popliteal blood flow, and heart rate were measured throughout the protocol. Loaded breathing to task failure increased mean arterial pressure in both sedentary and endurance-trained individuals (96±3 to 100±4 mmHg and 101±3 to 110±5 mmHg). Popliteal blood flow decreased in sedentary but not in trained individuals (0.179±0.01 to 0.141±0.01 cm/s, and 0.211±0.02 to 0.214±0.02 cm/s). Similarly, popliteal vascular resistance increased in sedentary but not in trained individuals (559±35 to 757±56 mmHg s/cm, and 528±69 to 558±64 mmHg s/cm). These data demonstrate that endurance-trained individuals have an attenuated inspiratory muscle metaboreflex.     

Idiopathic diaphragmatic paralysis—Satisfactory improvement of inspiratory muscle function by inspiratory muscle training

Daily inspiratory muscle strength and endurance training (IMT) was performed in a 44-year-old patient with idiopathic bilateral diaphragmatic paralysis (BDP) in addition to nocturnal non-invasive ventilation (NIV). After 4 months of training inspiratory muscle function improved satisfactorily whereas phrenic nerve latency remained pathological. Due to the improvement of inspiratory muscle capacity nocturnal NIV could be stopped without inducing nocturnal respiratory insufficiency.     

Mouth pressure twitches induced by cervical magnetic stimulation to assess inspiratory muscle fatigue

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% V(O(2),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 cmH(2)O and from 19.4+/-4.9 to 17.7+/-4.5 cmH(2)O, 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.     

Oxygen uptake kinetics and maximal aerobic power are unaffected by inspiratory muscle training in healthy subjects where time to exhaustion is extended

The aim of this study was to determine whether 4 weeks of inspiratory muscle training (IMT) would be accompanied by alteration in cardiopulmonary fitness as assessed through moderate intensity oxygen uptake (O₂) kinetics and maximal aerobic power (O_2max). Eighteen healthy males agreed to participate in the study [training group (Tra) n=10, control group (Con) n=8]. Measurements of spirometry and maximal static inspiratory mouth pressure (PI_max) were taken pre- and post-training in addition to: (1) an incremental test to volitional exhaustion, (2) three square-wave transitions from walking to running at a moderate intensity (80% ventilatory threshold) and (3) a maximal aerobic constant-load running test to volitional fatigue for the determination of time to exhaustion (T_lim). Training was performed using an inspiratory muscle trainer (Powerbreathe). There were no significant differences in spirometry either between the two groups or when comparing the post- to pre-training results within each group. Mean PI_max increased significantly in Tra (P<0.01) and showed a trend for improvement (P<0.08) in Con. Post-training T_lim was significantly extended in both Tra [232.4 (22.8) s and 242.8 (20.1) s] (P<0.01) and Con [224.5 (19.6) and 233.5 (12.7) s] (P<0.05). Post-training T_lim was significantly extended in Tra compared to Con (P<0.05). In conclusion, the most plausible explanation for the stability in O₂ kinetics and O_2max following IMT is that it is due to insufficient whole-body stress to elicit either central or peripheral cardiopulmonary adaptation. The extension of post-training T_lim suggests that IMT might be useful as a stratagem for producing greater volumes of endurance work at high ventilatory loads, which in turn could improve cardiopulmonary fitness.     

Effect of posture on inspiratory muscle electromyogram response to hypercapnia

Summary The aim of our study was to examine the effect of posture on inspiratory muscle activity response to hypercapnia. Recent research has revealed that in normal subjects the activation of the rib cage muscles and of the diaphragm is actually greater in the upright than in the supine position during resting tidal breathing. In this study we examined whether the upright position necessarily entails a greater activation of the inspiratory muscles also under conditions of ventilatory stress. For this purpose we compared the responses to CO₂-rebreathing in the supine and sitting positions in five volunteers, by simultaneously recording the electromyogram of the diaphragm (EMG_di) and the intercostal muscles (EMG_int). The electromyogram was recorded by means of surface electrodes to measure the EMG amplitude. While the slopes of ventilatory (V _E) response to increasing arterial CO₂ tension (P _aCO₂) were similar in the two positions, both the EMG_di-V _E and EMG_int-V _E relationship showed steeper slopes in the supine than in the sitting position. In each CO₂ run the increases in EMG_di were linearly related to those in EMG_int. This relationship was not affected by the body position. These results suggested that, in spite of similar ventilatory responses to CO₂-rebreathing in the lying and sitting positions, the supine position, in humans, required a higher activation of the inspiratory muscles.     

Augmented peripheral chemoreflex in patients with heart failure and inspiratory muscle weakness

We hypothesized that heart failure patients with inspiratory muscle weakness (IMW) present greater peripheral chemoreflex responsiveness and augmented exercise ventilatory oscillation compared to patients with preserved inspiratory muscle strength. We studied 19 heart failure patients: 9 with IMW (maximal inspiratory pressure [PImax] < 70% of predicted) and 10 with preserved inspiratory muscle strength. Inspiratory muscle strength was measured via pressure transducer. Peripheral chemoreflex was evaluated by the single-breath CO₂ test. Exercise ventilatory oscillation was determined as the ratio between amplitude and mean of each oscillation during incremental exercise. Patients with IMW had greater peripheral chemoreflex response (0.11 ± 0.03 l min⁻¹ Torr⁻¹) than those with preserved inspiratory muscle strength (0.07 ± 0.03 l min⁻¹ Torr⁻¹, p = 0.02). Moreover, there was a significant and inverse correlation between PImax and peripheral chemoreflex response (r = −0.57, p = 0.01). Likewise, there was a significant and inverse correlation between PImax and ventilatory oscillations (r = −0.46, p = 0.04). Our findings indicate that IMW is linked to increased peripheral chemoreflex and augmented exercise ventilatory oscillation in patients with chronic heart failure.     

Effect of acetazolamide on respiratory muscle fatigue in humans

Previous studies have demonstrated that carbonic anhydrase inhibition with acetazolamide reduces exercise capacity. The mechanism responsible for this early fatigue is unclear, but may be partly mediated by impaired respiratory muscle function. Inspiratory muscle strength and endurance were assessed in seven healthy men (age 28 ± 5 yrs, ±SD) by measuring maximal inspiratory pressure (MIP) and time to task failure during a constant-load breathing test (CLBT), respectively, under control (CON) and acetazolamide (ACZ; 500 mg/8 h po for 3 days) conditions that were separated by two weeks and randomized between subjects. In addition, MIP was measured before and after moderate-intensity cycling exercise to fatigue while pulmonary gas exchange, plasma pH, and ventilation were measured during exercise. ACZ did not alter pulmonary function (FVC, FEV1, MVV) or MIP measured at rest (CON, −157 ± 47 vs. ACZ, −154 ± 45 cmH₂O, p > 0.05), but decreased time to task failure during the CLBT (CON, 1340 ± 820 vs. ACZ, 698 ± 434 s; p = 0.01). Exercise duration during cycling exercise was reduced (p = 0.003) with ACZ (1090 ± 254 s) compared to CON (1944 ± 532 s) in the presence of a significantly lower plasma pH and higher ventilation compared to control (p < 0.05). Compared to resting values, MIP was reduced (p = 0.03) in ACZ but not CON at exhaustion. In conclusion, carbonic anhydrase inhibition with ACZ is associated with impaired respiratory muscle function at rest and following constant load cycling which may contribute to reduced exercise tolerance with carbonic anhydrase inhibition.     

A comparison of inspiratory muscle fatigue following maximal exercise in moderately trained males and females

Exercise-induced inspiratory muscle fatigue (IMF) has been reported in males but there are few reports of IMF in females. It is not known if a gender difference exists for inspiratory muscle strength following heavy exercise, as is reported in locomotor muscles. Therefore, the relationship between fatigue and subsequent recovery of maximal inspiratory pressure (MIP) following exercise to maximal oxygen consumption was examined in a group of moderately trained males and females. Eighteen males (23±3 years; mean ± SD) and 16 females (23±2 years) completed ten MIP and ten maximal handgrip (HG) strength maneuvers to establish baseline. Post-exercise MIP and HG were assessed successively immediately following a progressive intensity test on a cycle ergometer and at 1, 2, 3, 4, 5, 10, and 15 min. relative to fat-free mass was not statistically different between males (62±7 ml kg^–1 min^–1) and females (60±8 ml kg^–1 min^–1). Males had higher absolute MIP values than females at all time intervals (P<0.05). Immediately following exercise, MIP was significantly reduced in both genders (M=83±16%; F=78±15% of baseline) but HG values were not different than resting values. MIP values remained depressed for both males and females throughout the 15 min (P<0.05). Differences for MIP between males and females were not statistically significant at any measurement time (P>0.05). The findings in this study conclude that IMF, observed immediately following maximal exercise, demonstrated the same pattern of recovery for both genders.     

Effect of the leg muscle pump on the rise in muscle perfusion during muscle work in humans

The transient and steady-state effects of the calf muscle pump on the rise in muscle perfusion during rhythmic plantarflexions were investigated in 20 volunteers. Because a large hydrostatic column would increase the effect of a muscle pump, exercise in the supine and head-up tilted positions was compared. Within ~15 s of the start of muscle work, femoral artery flow (ultrasound Doppler) rose 0.37 L/min above rest in the supine and 0.5 L/min above rest in the tilted position. The latter is a significantly larger rise (P < 0.05). After 80 s of muscle work, femoral flow was stable at 0.38 and 0.39 L/min above rest in the supine and tilted positions, respectively. We conclude that the muscle pump contributes to muscle perfusion during the initial phase of muscle work, but that metabolic vasodilation is a more important determinant of muscle perfusion during steady-state muscle work.     

Acute and chronic responses of the upper airway to inspiratory loading in healthy awake humans: an MRI study

We assessed upper airway responses to acute and chronic inspiratory loading. In Experiment I, 11 healthy subjects underwent T(2)-weighted magnetic resonance imaging (MRI) of upper airway dilator muscles (genioglossus and geniohyoid) before and up to 10 min after a single bout of pressure threshold inspiratory muscle training (IMT) at 60% maximal inspiratory mouth pressure (MIP). T(2) values for genioglossus and geniohyoid were increased versus control (p<0.001), suggesting that these airway dilator muscles are activated in response to acute IMT. In Experiment II, nine subjects underwent 2D-Flash sequence MRI of the upper airway during quiet breathing and while performing single inspirations against resistive loads (10%, 30% and 50% MIP); this procedure was repeated after 6 weeks of IMT. Lateral narrowing of the upper airway occurred at all loads, whilst anteroposterior narrowing occurred at the level of the laryngopharynx at loads > or =30% MIP. Changes in upper airway morphology and narrowing after IMT were undetectable using MRI.     

Effect of graded changes in extracellular muscle volume on cardiovascular drives during static exercise

Summary The effects of graded changes in peripheral extracellular volume on heart rate and blood pressure during isometric exercise were studied in 12 healthy male subjects. Each subject performed four calf ergometer tests with each calf. In all tests, static plantar flexion of one foot was performed in a supine body position with the knee joint flexed to 90°. After a pre-exercise period of 18 min, during which the calf volume was manipulated, the subjects had to counteract a spring force of 120 N for 8 min. In the pre-exercise period the peripheral extracellular volume of the calf muscle to be tested was manipulated in four ways. Test 1: 15 min of rest in the exercise position. During the last 3.5 min, the calf volume was increased by venous congestion [80 mmHg (10.67 kPa) applied to the distal part of the thigh by pneumatic cuff]. Test 2: the same protocol as in test 1 but with 7.5-min venous congestion. Test 3: 15 min of venous congestion. Test 4: the calf volume was decreased by a negative hydrostatic pressure for 15 min (calf raised about 40 cm above heart level). To clamp the changed calf volume, the thigh cuff was rapidely inflated to 300 mmHg (40.0 kPa) at the end of the volume manipulation and the subjects remained resting for a further 3 min. In test 4, the leg of the subject was passively brought into the exercise position. The occlusion was maintained until 2 min after exercise. The calf volume manipulation led to changes ranging from +105 ml (test 3) to –134 ml (test 4) as measured by water displacement plethysmography. The blood pressure response to exercise was inversely related to the calf volume changes while the heart rate response during exercise showed no clearcut relationship to the pretreatments.     

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.     

Effect of exercise to exhaustion on myeloperoxidase and lysozyme release from blood neutrophils

Exercise sessions (swimming in rats and treadmill running in humans) resulted in stimulation of neutrophil degranulation in the experiments with animals and in the human study. Myeloperoxidase (MPO) (+67%) and lysozyme (+51%) quantities in the plasma of rats increased significantly immediately after exercise. The blood plasma lysozyme concentration was increased by 41% at the 6th min of treadmill exercise in athletes. The blood concentrations of neutrophil proteins normalized both in humans and animals at rest. The neutrophil protein concentrations in blood increased in parallel with the decrease of their level in leukocytes. The neutrophil capacity for an oxidative burst was not changed by the exercise, but decreased for 3–6 h in the post-exercise period. Such dynamics of the oxidative burst activity suggest a lack of association between this parameter and the degranulation process. The neutrophil proteins that appear in blood during degranulation can be involved in enhancing the bactericidal potency of blood, the activation of granulopoiesis, neutrophil efflux from bone marrow, and the conditioning of blood endothelium for leukocyte extravasation. Electronic Publication     

Consequences of exercise-induced respiratory muscle work

We briefly review the evidence for a hypothesis, which links the ventilatory response to heavy intensity, sustained exercise-to-exercise performance limitation in health. A key step in this linkage is a respiratory muscle fatigue-induced metaboreflex, which increases sympathetic vasoconstrictor outflow, causing reduced blood flow to locomotor muscles and locomotor muscle fatigue. In turn, the limb fatigue comprises an important dual contribution to both peripheral and central fatigue mechanisms, which contribute to limiting exercise performance. Clinical implications for respiratory limitations to exercise in patients with chronic obstructive lung disease (COPD) and chronic heart failure (CHF) are discussed and key unresolved problems are outlined.     

Effects of prolonged exercise to exhaustion on left-ventricular function and pulmonary gas exchange

The purpose of this study was to simultaneously examine left-ventricular (LV) function and pulmonary gas exchange during prolonged constant-rate cycling in an attempt to explain the exercise-induced impairment in gas exchange. Eleven competitive cyclists rode their racing bicycles on a computerized cycle trainer at 25 W below the lactate threshold until exhaustion (exercise time = 2.51 +/- 0.86 h). LV systolic function was evaluated with two-dimensional echocardiography while arterial blood gases were used to assess pulmonary gas exchange. All variables were assessed concurrently before, during, and after exercise. LV function and cardiac output increased at the onset of exercise and were maintained until exhaustion. The alveolar-arterial P(O(2)) difference (A-a D(O(2))) increased within 15 min of the onset of exercise, was unchanged through to exhaustion, and returned to baseline 5 min post-exercise. Gas exchange was not related to cardiovascular function at the onset, or at end exercise. The results indicate that the widening A-aD(O(2)) during exercise is due to a readily reversible change in gas exchange function.     

Heterogeneity of response to exercise of rat muscle pyruvate dehydrogenase complex

Muscle glucose uptake is greatly stimulated by moderate exercise, but full oxidation of the glucose to CO₂ depends on the activity of the pyruvate dehydrogenase (PDH) complex. Our aim was to determine how PDH complex in different muscle groups responds to varying periods of moderate exercise. Rats were run on a motor-driven treadmill for 5–30 min and muscle PDH complex activity was determined in heart, diaphragm and red quadriceps muscles after isolation of mitochondria in the presence of inhibitors of PDH complex interconversion. In heart and diaphragm muscle, exercise caused an increase in PDH complex activity after 5 min, but this was followed by a significant decrease in activity as exercise progressed. In red quadriceps muscle, PDH complex activity was reduced after 5 min of exercise and was decreased further as exercise continued. We conclude that increased duration of exercise can lead to reduced PDH complex activity in rat muscles. We propose that this is a consequence of elevated fatty acid oxidation, the products of which stimulate PDH kinase. This implies that increased glycolysis to lactate and increased fatty acid oxidation can simultaneously provide energy for contracting muscle.     

低氧复合运动对大鼠骨骼肌线粒体含量的影响

 目的：探讨低氧复合运动对线粒体含量的影响及线粒体生物合成和自噬在其中的作用。方法：雄性SD大鼠随机分为常氧对照（NC）组、常氧运动（NT）组、低氧对照（HC）组和低氧复合运动（HT）组。低氧干预为常压低氧帐篷,11.3%氧浓度持续暴露4周。运动干预为跑台训练（5°,15 m/min）,60 min/d,每周5 d,共4周。JC-1荧光探针检测线粒体膜电位;萤光素酶法检测线粒体ATP合成能力;Western blotting检测骨骼肌过氧化物酶体增殖物激活受体γ辅激活因子1（PGC-1α）、线粒体转录因子A（Tfam）、Bcl-2/腺病毒E1B 19kD相互作用蛋白3（Bnip3）、苄氯素1（beclin-1）、细胞色素C氧化酶亚基IV（COXIV）和电压依赖性阴离子通道1（VDAC-1）蛋白表达量。结果：HC组与NC组比较,线粒体膜电位、ATP合成能力及COXIV、VDAC-1、PGC-1α和Tfam蛋白表达显著降低（P<005或P<001）,Bnip3和beclin-1蛋白表达显著升高（P<005）。HT组与HC组比较,线粒体膜电位、ATP合成能力及COXIV、VDAC-1、PGC-1α、Tfam、Bnip3和beclin-1蛋白表达均显著升高（P<005或P<001）。结论：慢性低氧暴露提高了线粒体自噬但抑制了线粒体生物合成,导致线粒体含量减少。低氧复合运动促进低氧状态下骨骼肌线粒体自噬,并促进线粒体生物合成,从而提高线粒体含量及功能。     

Effects of increased muscle perfusion pressure on responses to dynamic leg exercise in man

Summary Ventilatory, cardiovascular and metabolic functions and work performance were studied in men performing incremental-load dynamic leg exercise until exhaustion.Part I: Responses to supine exercise were investigated in 8 subjects during exposure of the lower body to subatmospheric pressure at –6.67 kPa (–50 mm Hg) (Lower Body Negative Pressure, LBNP). Due to curtailment of stroke volume, cardiac output was reduced by LBNP over a wide range of work intensities, including heavy loads: ventilation, oxygen uptake and blood lactate concentrations increased with work load, but at lower rates than in the control condition.Part II: In 9 subjects, work performance was compared in three conditions: supine exercise with and without LBNP, and upright exercise. Performance in supine exercise was enhanced by LBNP, and was further improved in upright exercise. In supine exercise, the LBNP-induced reduction in blood lactate and enhancement of work performance are attributed to a more efficient muscle blood flow resulting from increased local perfusion pressure. This strongly suggests that the primary limitation of work performance was set by the peripheral circulation in working muscles rather than by cardiac performance. A similar mechanism may, in part, explain why work performance in dynamic leg exercise was greater in the upright than in the supine posture. It is also concluded that supine leg exercise during LBNP is a useful model of upright exercise, with regard to the central circulation and the circulation in working muscles.     

Effects of dynamic ischaemic training on human skeletal muscle dimensions

The effect of training under conditions of local leg ischaemia on muscle area and fibre dimensions was studied in nine males. Leg ischaemia was induced by enclosing the legs in a pressure chamber and sealing the opening with a rubber membrane at the level of the crotch. Air pressure over the legs was 50 mmHg. The subjects performed 16 sessions (45 min) of one-legged supine strenuous ischaemic training during 4 weeks. Exercise intensity was maintained as high as possible during the whole session. The contralateral leg served as a control leg and remained passive during exercise. Before and after the training period, muscle fibre dimensions were determined from biopsy samples taken from the m. vastus lateralis, and leg muscle dimensions were assessed by magnetic resonance imaging (MRI). In the trained leg, mean fibre area increased by 12% (P < 0.05). The MRI-assessed cross-sectional area of the vastus group increased by 4% (P=0.01). In the control leg, mean fibre area and the cross-sectional area of the vastus group were unchanged, while those of the adductor muscle group decreased by 4% (P < 0.05). It is concluded that a short period of strenuous ischaemic endurance training increases the cross-sectional area of the ischaemically trained muscle group, as measured both by MRI and from muscle biopsy samples. In contrast, the adductor muscles in the contralateral thigh showed a decreased cross-sectional area (as assessed by MRI), possibly due to the effects of the strenuous contralateral training, by mechanisms that have yet to be identified. Accepted: 26 December 1999