Cellular and molecular responses to increased skeletal muscle loading after irradiation

Irradiation of rat skeletal muscles before increased loading has been shown to prevent compensatory hypertrophy for periods of up to 4 wk, possibly by preventing satellite cells from proliferating and providing new myonuclei. Recent work suggested that stem cell populations exist that might allow irradiated muscles to eventually hypertrophy over time. We report that irradiation essentially prevented hypertrophy in rat muscles subjected to 3 mo of functional overload (OL-Ir). The time course and magnitude of changes in cellular and molecular markers of anabolic and myogenic responses were similar in the OL-Ir and the contralateral nonirradiated, overloaded (OL) muscles for the first 3-7 days. These markers then returned to control levels in OL-Ir muscles while remaining elevated in OL muscles. The number of myonuclei and amount of DNA were increased markedly in OL but not OL-Ir muscles. Thus it appears that stem cells were not added to the irradiated muscles in this time period. These data are consistent with the theory that the addition of new myonuclei may be required for compensatory hypertrophy in the rat.     

Human responses to propionic acid. II. Quantification of breathing responses and their relationship to perception

In 20 normal and four anosmic participants, instantaneous inhalation and exhalation flow rates were recorded in response to 15 s stimulations with clean air or propionic acid concentrations (0.16, 1.14, 8.22 and 59.15 p.p.m., v/v) that ranged from peri-threshold for normals to clearly supra-threshold for anosmics. Each odorant/irritant delivery to the face-mask began with an exhalation. This allowed concentration to reach full value before stimulus onset, defined as the point where the participant began to bring the stimulus into the nose by inhalation. Two seconds after this stimulus onset, normals exhibited cumulative inhaled volume (CIV) declines of 39 and 14%, and latencies of 500 and 710 ms, with presentations of 59.15 and 8.22 p.p.m., respectively. With anosmics, 59.15 p.p.m. caused a 19% decline in CIV that began at 730 ms. Examination of the first inhalation after stimulus onset shows that the CIV declines in normals were achieved by a progressive decline in volume (InVol), beginning with a slight drop at 1.14 p.p.m., and a marked decline in duration (InDur) with only the highest concentration. Anosmics exhibited declines in InDur and InVol with only the 59.15 p.p.m. stimulus, and these declines were much more modest than the changes seen in normals. Comparison of these breathing results with perceptual responses from this same experiment demonstrates that: (i) in normals, odor perception rises slightly, but breathing does not change, with the lowest concentration; (ii) the higher breathing sensitivity (declines in InVol) of normals is paralleled by both the higher nasal irritation of these individuals and the presence of odor sensation; (iii) InDur declines in normals only with a stimulus concentration sufficient to cause marked nasal irritation in anosmics; and iv) in anosmics, modest but reliable declines in both InDur and InVol mirror the marked elevation in nasal irritation magnitude seen with only the highest concentration. In view of the failure of prior work to provide evidence that olfactory activation alone can cause any of the breathing changes we observed, we conclude that some breathing parameters are quite useful as rapid and sensitive measures of nasal irritation that arises from activation of nasal trigeminal afferents alone or in combination with the olfactory nerve.     

Effect of inspiratory muscle fatigue on breathing pattern during inspiratory resistive loading

The purpose of this study was to determine whether induction of either inspiratory muscle fatigue (expt 1) or diaphragmatic fatigue (expt 2) would alter the breathing pattern response to large inspiratory resistive loads. In particular, we wondered whether induction of fatigue would result in rapid shallow breathing during inspiratory resistive loading. The breathing pattern during inspiratory resistive loading was measured for 5 min in the absence of fatigue (control) and immediately after induction of either inspiratory muscle fatigue or diaphragmatic fatigue. Data were separately analyzed for the 1st and 5th min of resistive loading to distinguish between immediate and sustained effects. Fatigue was achieved by having the subjects breathe against an inspiratory threshold load while generating a predetermined fraction of either the maximal mouth pressure or maximal transdiaphragmatic pressure until they could no longer reach the target pressure. Compared with control, there were no significant alterations in breathing pattern after induction of fatigue during either the 1st or 5th min of resistive loading, regardless of whether fatigue was induced in the majority of the inspiratory muscles or just in the diaphragm. We conclude that the development of inspiratory muscle fatigue does not alter the breathing pattern response to large inspiratory resistive loads.     

Effort sensation, chemoresponsiveness, and breathing pattern during inspiratory resistive loading.

Although inspiratory resistive loading (IRL) reduces the ventilatory response to CO2 (VE/PCO2) and increases the sensation of inspiratory effort (IES), there are few data about the converse situation: whether CO2 responsiveness influences sustained load compensation and whether awareness of respiratory effort modifies this behavior. We studied 12 normal men during CO2 rebreathing while free breathing and with a 10-cmH2O.l-1.s IRL and compared these data with 5 min of resting breathing with and without the IRL. Breathing pattern, end-tidal PCO2, IES, and mouth occlusion pressure (P0.1) were recorded. Free-breathing VE/PCO2 was inversely related to an index of effort perception (IES/VE; r = -0.63, P less than 0.05), and the reduction in VE/PCO2 produced by IRL was related to the initial free-breathing VE/PCO2 (r = 0.87, P less than 0.01). IRL produced variable increases in inspiratory duration (TI), IES, and P0.1 at rest, and the change in tidal volume correlated with both VE/PCO2 (r = 0.63, P less than 0.05) and IES/VE (r = -0.69, P less than 0.05), this latter index also predicting the changes in TI with loading (r = -0.83, P less than 0.01). These data suggest that in normal subjects perception of inspiratory effort can modify free-breathing CO2 responsiveness and is as important as CO2 sensitivity in determining the response to short-term resistive loading. Individuals with good perception choose a small-tidal volume and short-TI breathing pattern during loading, possibly to minimize the discomfort of breathing.     

A new method to measure nasal impedance in spontaneously breathing adults

As an alternative to standard rhinomanometric methods, we applied forced oscillations at the mouth in five normal subjects and determined their nasal impedance with a novel method involving flow subtraction. Pressure oscillations of constant amplitude were applied at the mouth of a subject both when the nostrils were open and when they were closed with a noseclip. The airflows measured under the two conditions were subtracted to yield the oscillating nasal airflow at the imposed pressure. The resultant pressure-flow relation defined the nasal impedance of the subject. For frequencies between 3 and 15 Hz, the transnasal pressure-flow relation was well described by a linear lumped parameter model consisting of a resistive and inertial element. Nasal resistance obtained with flow subtraction did not differ significantly from control measurements obtained while the subjects performed the Valsalva maneuver. In contrast, nasal inertance obtained with flow subtraction was approximately twice that obtained with the Valsalva method. The difference between inertances may reflect structural changes in nasopharyngeal dimensions that occur with the Valsalva maneuver. We conclude that the mechanical impedance of the nasal passage may be determined during spontaneous breathing from the response to imposed forced oscillations at the mouth. The noninvasive nature of this method suggests that it may be simpler to implement than traditional rhinomanometric methods.     

Motor responses to positive-pressure breathing in the developing opossum

The suckling opossum exhibits an expiration-phased discharge in abdominal muscles during positive-pressure breathing (PPB); the response becomes apparent, however, only after the 3rd-5th wk of postnatal life. The purpose of this study was to determine whether the early lack of activation represented a deficiency of segmental outflow to abdominal muscles or whether comparable effects were observed in cranial outflows to muscles of the upper airways due to immaturity of afferent and/or supraspinal pathways. Anesthetized suckling opossums between 15 and 50 days of age were exposed to PPB; electromyogram (EMG) responses in diaphragm and abdominal muscles were measured, along with EMG of larynx dilator muscles and/or upper airway resistance. In animals older than approximately 30 days of age, the onset of PPB was associated with a prolonged expiration-phased EMG activation of larynx dilator muscles and/or decreased upper airway resistance, along with expiratory recruitment of the abdominal muscle EMG. These effects persisted as long as the load was maintained. Younger animals showed only those responses related to the upper airway; in fact, activation of upper airway muscles during PPB could be associated with suppression of the abdominal motor outflow. After unilateral vagotomy, abdominal and upper airway motor responses to PPB were reduced. The balance between PPB-induced excitatory and inhibitory or disfacilitory influences from the supraspinal level on abdominal motoneurons and/or spinal processing of information from higher centers may shift toward net excitation as the opossum matures.     

Antioxidant responses of cortex neurons to iron loading

Brain cells have a highly active oxidative metabolism, yet they contain only low to moderate superoxide dismutase and catalase activities. Thus, their antioxidant defenses rely mainly on cellular reduced glutathione levels. In this work, in cortical neurons we characterized viability and changes in reduced and oxidized glutathione levels in response to a protocol of iron accumulation. We found that massive death occurred after 2 days in culture with 10 microM Fe. Surviving cells developed an adaptative response that included increased synthesis of GSH and the maintenance of a glutathione-based reduction potential. These results highlight the fundamental role of glutathione homeostasis in the antioxidant response and provide novel insights into the adaptative mechanisms of neurons subjected to progressive iron loads.     

Neuromuscular responses to explosive and heavy resistance loading

The EMG power spectrum may shift towards higher frequencies with higher movement velocities. Fatigue, on the other hand, can cause a decrease in the frequency components. The purpose of this study was to examine acute effects of explosive (EE) and heavy resistance (HRE) concentric leg press exercise on muscle force, EMG and blood lactate. The EE included five sets of ten repetitions with 40±6% of the isometric maximum at a 100° knee angle performed as explosively as possible. The same number of repetitions was performed in HRE but with a heavier load (67±7% of the isometric maximum at a 100° knee angle). Maximal isometric and single concentric actions of different loads, and an isometric fatigue test were measured before and after both exercises. Surface EMG was recorded from the vastus medialis muscles for analyses of average EMG (aEMG) and EMG power spectrum. Muscle fiber composition of the vastus lateralis was determined and blood lactate measured throughout the exercises. Mean power frequency and median frequency were higher during EE than during HRE (P<0.05). They increased during EE (P<0.05) as the exercise progressed, whereas during HRE no change or even slight decreases were observed. Signs of fatigue after pure concentric work were not observed after EE, and even after HRE, possibly due to the relatively small range of motion and short duration of action time, the fatigue was not that extensive. The relative number of fast twitch fibers was correlated (r=0.87, P<0.05) with the change in blood lactate in HRE. It was concluded that there may be a greater use of fast twitch motor units in explosive movements and that instead of fatigue, the present number of concentric actions in explosive exercise seems to have facilitated the neuromuscular system.