[Biology of muscle injury and repair].
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Humans↗
Biomedical subjects
A Grassino
Publications and source records attributed to A Grassino.
Expression of myosin heavy-chain isoforms in the respiratory muscles following inspiratory resistive breathing.
We investigated the effect of inspiratory resistive breathing (IRB) on the expression of the genes encoding fast and slow isoforms of myosin heavy chain (MyHC) in respiratory muscles. Eleven mongrel dogs were studied for baseline MyHC messenger RNA (mRNA) expression, seven of which were also used to study the effects of IRB. For this latter objective, awake and spontaneously breathing animals were subjected to 2 h of IRB (80 cm H(2)O/L/s) per day for four consecutive days. mRNA expression was assessed in the diaphragm, external intercostal muscle, and a limb muscle, using both slot- blot and in situ hybridizations with isoform-specific probes. A current semiquantitative scoring method (from 0 to 4) was used to quantify the in situ mRNA expression levels, and slot-blot data were analyzed with densitometry. Prior to IRB, slow- and fast-MyHC mRNA expression was moderate, similar, and homogeneous throughout the different regions of the diaphragm, with scores of 1.50 +/- 0.54 (mean +/- SD) for slow and 2.13 +/- 0.35 for fast mRNAs in the costal region of the diaphragm, and of 1.81 +/- 0.37 for slow and 2. 13 +/- 0.64 for fast mRNAs in the crural region of the diaphragm. Although expression of fast-MyHC mRNA remained unchanged after IRB, the relative expression of the mRNA for the slow isoform increased in costal (+30%), crural (+12%), and external intercostal (+27%) muscles. MyHC mRNA expression did not change in limb muscles. We conclude that breathing with a moderate inspiratory resistance for a short period induces the expression of slow MyHC in respiratory muscles.
Animals↗
Chronic alveolar hypoventilation helps to maintain the inspiratory muscle effort of COPD patients within sustainable limits.
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Biomechanical Phenomena↗
Influence of atracurium on the diaphragm mean action potential conduction velocity in canines.
BACKGROUND: It has been shown that progressive neuromuscular blockade (NMB) affects the electromyogram power spectrum and compound muscle action potential duration in skeletal muscle. These measures are linked to the mean muscle action potential conduction velocity (APCV), but no studies have confirmed a relation between the mean APCV and NMB. The aim of this study was to determine whether diaphragm mean APCV is affected by NMB. METHODS: The effects of NMB on diaphragm mean APCV were evaluated in five mongrel dogs. Progressive NMB was induced by slow intravenous infusion of atracurium. During spontaneous breathing, the diaphragm mean APCV was determined by electromyogram signals, in the time and frequency domains. The magnitude of NMB was quantified by the amplitude of the compound muscle action potential and by changes in muscle shortening during supramaximal stimulation of the phrenic nerve. RESULTS: Progressive NMB was associated with a decrease in diaphragm mean APCV. At approximately 70% reduction in the compound muscle action potential amplitude, diaphragm mean APCV had decreased more than 20%. Recovery after NMB was characterized by a restoration of the mean APCV to control values. CONCLUSION: This study shows that progressive NMB paralyzes motor units within the diaphragm in an orderly manner, and the blockade first affects muscle fibers with high APCV before it affects fibers with lower APCV.
Action Potentials↗
CO2-response in chronic obstructive pulmonary disease.
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Carbon Dioxide↗
Crural diaphragm activation during dynamic contractions at various inspiratory flow rates.
The purpose of this study was to evaluate the influence of velocity of shortening on the relationship between diaphragm activation and pressure generation in humans. This was achieved by relating the root mean square (RMS) of the diaphragm electromyogram to the transdiaphragmatic pressure (Pdi) generated during dynamic contractions at different inspiratory flow rates. Five healthy subjects inspired from functional residual capacity to total lung capacity at different flow rates while reproducing identical Pdi and chest wall configuration profiles. To change the inspiratory flow rate, subjects performed the inspirations while breathing across two different inspiratory resistances (10 and 100 cmH2O . l-1 . s), at mouth pressure targets of -10, -20, -40, and -60 cmH2O. The diaphragm electromyogram was recorded and analyzed with control of signal contamination and electrode positioning. RMS values obtained for inspirations with identical Pdi and chest wall configuration profiles were compared at the same percentage of inspiratory duration. At inspiratory flows ranging between 0.1 and 1.4 l/s, there was no difference in the RMS for the inspirations from functional residual capacity to total lung capacity when Pdi and chest wall configuration profiles were reproduced (n = 4). At higher inspiratory flow rates, subjects were not able to reproduce their chest wall displacements and adopted different recruitment patterns. In conclusion, there was no evidence for increased demand of diaphragm activation when healthy subjects breathe with similar chest wall configuration and Pdi profiles, at increasing flow rates up to 1.4 l/s.
Adult↗
Effects of lung volume on diaphragm EMG signal strength during voluntary contractions.
The use of esophageal recordings of the diaphragm electromyogram (EMG) signal strength to evaluate diaphragm activation during voluntary contractions in humans has recently been criticized because of a possible artifact created by changes in lung volume. Therefore, the first aim of this study was to evaluate whether there is an artifactual influence of lung volume on the strength of the diaphragm EMG during voluntary contractions. The second aim was to measure the required changes in activation for changes in lung volume at a given tension, i.e., the volume-activation relationship of the diaphragm. Healthy subjects (n = 6) performed contractions of the diaphragm at different transdiaphragmatic pressure (Pdi) targets (range 20-160 cmH2O) while maintaining chest wall configuration constant at different lung volumes. The diaphragm EMG was recorded with a multiple-array esophageal electrode, with control of signal contamination and electrode positioning. The effects of lung volume on the EMG were studied by comparing the crural diaphragm EMG root mean square (RMS), an index of crural diaphragm activation, with an index of global diaphragm activation obtained by normalizing Pdi to the maximum Pdi at the given muscle length (Pdi/Pdimax@L) at the different lung volumes. We observed a direct relationship between RMS and Pdi/Pdimax@L independent of diaphragm length. The volume-activation relationship of the diaphragm was equally affected by changes in lung volume as the volume-Pdi relationship (60% change from functional residual capacity to total lung capacity). We conclude that the RMS of the diaphragm EMG is not artifactually influenced by lung volume and can be used as a reliable index of diaphragm activation. The volume-activation relationship can be used to infer changes in the length-tension relationship of the diaphragm at submaximal activation/contraction levels.
Adult↗
Voluntary activation of the human diaphragm in health and disease.
Intersubject comparison of the crural diaphragm electromyogram, as measured by an esophageal electrode, requires a reliable means for normalizing the signal. The present study set out 1) to evaluate which voluntary respiratory maneuvers provide high and reproducible diaphragm electromyogram root-mean-square (RMS) values and 2) to determine the relative diaphragm activation and mechanical and ventilatory outputs during breathing at rest in healthy subjects (n = 5), in patients with severe chronic obstructive pulmonary disease (COPD, n = 5), and in restrictive patients with prior polio infection (PPI, n = 6). In all groups, mean voluntary maximal RMS values were higher during inspiration to total lung capacity than during sniff inhalation through the nose (P = 0.035, ANOVA). The RMS (percentage of voluntary maximal RMS) during quiet breathing was 8% in healthy subjects, 43% in COPD patients, and 45% in PPI patients. Despite the large difference in relative RMS (P = 0.012), there were no differences in mean transdiaphragmatic pressure (P = 0.977) and tidal volumes (P = 0.426). We conclude that voluntary maximal RMS is reliably obtained during an inspiration to total lung capacity but a sniff inhalation could be a useful complementary maneuver. Severe COPD and PPI patients breathing at rest are characterized by increased diaphragm activation with no change in diaphragm pressure generation.
Adult↗
Diaphragm interference pattern EMG and compound muscle action potentials: effects of chest wall configuration.
The effect of chest wall configuration on the diaphragm electromyogram (EMGdi) was evaluated in five healthy subjects with an esophageal electrode for both interference pattern EMGdi (voluntary contractions) and electrically evoked diaphragm compound muscle action potentials (CMAPs). Diaphragm CMAPs (both unilateral and bilateral) were evaluated for the baseline-to-peak amplitude (Ampl), the time from the onset of the CMAP to first peak (T1), root mean square (RMS), and center frequency (CF) values of the CMAP power spectrum. CF values from the interference pattern EMGdi power spectrum were also calculated. For CMAPs obtained at an electrode position least influenced by variations induced by electrode positioning, Ampl increased with diaphragm shortening from functional residual capacity (FRC) to total lung capacity (TLC) by 101 and 98% (unilateral and bilateral, respectively). Bilateral CMAP RMS values increased 116% from FRC to TLC. CMAP T1 values decreased with diaphragm shortening from FRC to TLC by 1.1 and 2.1 ms for the unilateral and bilateral stimulations, respectively, and CF increased for the bilateral diaphragm CMAPs with diaphragm shortening. CF values from the interference pattern EMGdi did not show any consistent change with chest wall configuration. Thus CF values of the interference pattern EMGdi obtained with an esophageal electrode can be considered reliable for physiological interpretation, at any diaphragm length (if electrode positioning and signal contamination are controlled for), contrary to the diaphragm CMAPs, which are sensitive to changes in chest wall configuration. It is speculated that the different results (over the effects of chest wall configuration on interference pattern EMGdi and diaphragm CMAPs) amy be because of summation properties of the signals and how these influence the EMG power spectrum.
Action Potentials↗
Relationship between chronic hypercapnia and inspiratory-muscle weakness in myotonic dystrophy.
We studied 134 patients with Steinert's myotonic dystrophy (MD) in order to determine the prevalence of chronic hypercapnia, the level of muscle weakness and forced expiratory volume at which hypercapnic respiratory failure is likely to occur, and how clinical assessment might help predict hypercapnic respiratory failure. Subjects were divided into five classes with a muscular disability rating scale (MDRS): 0 = no clinical impairment (n = 9), I = minimal signs of impairment (n = 11), II = distal weakness (n = 41), III = moderate proximal weakness (n = 62), and IV = nonambulatory (n = 11). The prevalence of hypercapnia (PaCO2 > or = 43 mm Hg) was found to be 0%, 27%, 29%, 45% and 55% for MDRS 0 to 4, respectively (p = 0.03). A multiple regression analysis limited to clinical data showed that daytime hypersomnolence was a significant cofactor with the MDRS (p = 0.01) in predicting PaCO2 (r = 0.40). Among respiratory parameters, FVC, respiratory muscle strength (RMS), and maximal inspiratory pressure against occluded airways (PImax) were found to be predictors of nearly equal strength, explaining 16%, 15%, and 14% of the PaCO2 variance, respectively. In multiple regression analysis, sex, daytime sleepiness, and the expected/observed FVC ratio for a given RMS were found to be significant cofactors with PImax in predicting PaCO2 (r = 0.51). It is concluded that respiratory insufficiency should be suspected in MD patients with proximal weakness or daytime sleepiness. The likelihood of hypercapnia also increases with volume restriction and respiratory muscle weakness. Our study suggests that the combination of inspiratory muscle weakness and loading plays a predominant role in the pathogenesis of chronic alveolar hypoventilation in MD patients. The occurrence of daytime hypersomnolence suggests that other factors, such as low central ventilatory drive or sleep apnea, might play an additional role.
Chronic Disease↗
Electromyographical evidence for exercise-induced diaphragm fatigue in patients with chronic cervical cord injury or prior poliomyelitis infection.
UNLABELLED: The purpose of this study was to determine, in exercising patients, how much diaphragm force increases before electromyographical evidence of diaphragm fatigue occurs. The study was performed in ten male patients with complete cervical cord injury (CCI) at the C5 to C8 levels, and five male patients with prior poliomyelitis infection (PPI) requiring chronic treatment with intermittent positive pressure ventilation (IPPV) at night. We studied the time course of the diaphragmatic tension-time index (TTdi), the centre frequency (CFdi) of the diaphragm electromyogram (EMGdi) power spectrum, and the ventilatory parameters, during steady-state submaximal arm/leg exercise. During exercise, early signs of diaphragm fatigue were present in seven out of 10 CCI patients and in four out of five PPI patients, as indicated by a reduction in CFdi. The increase in TTdi achieved before reductions in CFdi occurred was twofold in both the CCI and PPI patients. All patients except for the PPI patients, who demonstrated a reduction in CFdi, showed an increase in minute ventilation (VE), achieved by increasing both their tidal volume (Vt) and the breathing frequency (fb). The PPI patients demonstrating reductions in CFdi during exercise also increased their VE however, this was achieved by increasing fb while Vt remained constant. Following the reductions in CFdi, the CCI patients further increased their TTdi throughout the exercise test, while the PPI patients reduced their TTdi values. IN CONCLUSION: (1) During exercise, electromyographical evidence for diaphragmatic fatigue frequently occurred in the CCI and PPI patients studied; (2) Compared to the eightfold increase in TTdi seen in healthy subjects before reductions in CFdi occur, the TTdi values increased only two-fold before electromyographical evidence of diaphragm fatigue was present in these patients; (3) There is a clear discrepancy between the CCI and PPI patients who demonstrate electromyographical evidence of diaphragm fatigue, in terms of their ventilatory and TTdi responses.
Adult↗
Diaphragm function in patients with cervical cord injury or prior poliomyelitis infection.
Diaphragm function was evaluated in cervical cord injury patients (CCI), 1-3 years after injury (CCI(1-3)) and 10 years or more after injury (CCI(> or = 10)), as well as in a group of prior poliomyelitis infection patients (PPI), requiring intermittent positive pressure ventilation (IPPV) for about 6 h per night. Measurements included transdiaphragmatic pressure swings (delta Pdi) at rest, during maximal inspiratory efforts against closed airways (delta Pdi(max)) and during sniff manoeuvres (ie maximal inhalation through the nose, delta Pdi(sniff)), vital capacity normalized to age and height (VC(%pred)), tidal volume (Vt), relative inspiratory time (Ti/Ttot), breathing frequency (f(b)), and the tension-time index of the diaphragm (TTdi = delta Pdi/delta Pdi(max) x Ti/Ttot). The median VC(%pred) was 50% in the CCI(1-3) group and 57% in the CCI (> or = 10) group, but only 28% in the PPI group. Delta Pdi(max) values were similar for the CCI(1-3) (11.8 kPa) and CCI(> or = 10) (11.9 kPa) groups but were lower (71. kPa) in the PPI group. Due to the reduction in delta Pdi(max), the PPI group had higher delta Pdi/delta Pdi(max) values than the CCI groups, however, the TTdi was similar amongst the different groups studied. A submaximal exercise test in five cervical cord injury patients and in five polio patients with similar delta Pdi(max), delta Pdi(sniff) and TTdi values at rest revealed clear group differences with respect to force development, in that CCI patients showed significant increases in TTdi, while PPI demonstrated only minor changes. In CCI patients, an increase in ventilation was accompanied by an increase in delta Pdi/delta Pdi(max) while in contrast, the PPI patients showed no increase in delta Pdi/delta Pdi(max). We conclude that CCI patients, both recently and previously injured, have a similar maximal inspiratory force and are less impaired than the PPI patients. The TTdi at rest is similar in all groups, but the PPI patients react to inspiratory loads with little increases in TTdi, while the CCI patients increase their TTdi above fatiguing (0.15) levels. The different behaviours may be linked to loss of sensory pathways in the CCI patients.
Adult↗
Effects of pursed-lips breathing and expiratory resistive loading in healthy subjects.
To examine the effect of pursed-lips breathing (PLB) on breathing pattern and respiratory mechanics, we studied 11 healthy subjects breathing with and without PLB at rest and during steady-state bicycle exercise. Six of these subjects took part in a second study, which compared the effects of PLB to expiratory resistive loading (ERL). PLB was found to prolong expiratory and total breath durations and to promote a slower and deeper breathing pattern. During exercise, the compensatory increase that occurred in tidal volume was not sufficient to counter the reduction in breathing frequency, causing minute ventilation to be reduced. Although ERL similarly caused minute ventilation and breathing frequency to be decreased, unlike PLB, it produced no change in tidal volume and prolonged expiratory and total breath durations to a lesser extent. PLB and ERL increased the expiratory resistance to a comparable degree, also increasing the expiratory resistive work of breathing and promoting greater expiratory rib cage and abdominal muscle recruitment in response to the expiratory loads. End-expiratory lung volume, which was determined from inspiratory capacity maneuvers, was not altered by PLB; however, with ERL it was increased by 0.20 and 0.24 liter during rest and exercise, respectively. Inspiratory muscle recruitment patterns were not altered by PLB at rest, although small increases in the relative contribution of the rib cage/accessory muscles in conjunction with abdominal muscle relaxation occurred during exercise. Similar trends were observed with ERL. We conclude that, although ERL and PLB induce comparable respiratory muscle recruitment responses, they are not equivalent with respect to breathing pattern changes and effect on end-expiratory lung volume.
Adult↗
Influence of bipolar esophageal electrode positioning on measurements of human crural diaphragm electromyogram.
We aimed to describe how the human diaphragm electromyogram (EMGdi) is filtered at different positions within the esophageal hiatus, i.e., in the close proximity of the diaphragm, when obtained with an array of bipolar electrode pairs mounted on an esophageal catheter. We defined the electrically active crural diaphragm musculature that covers the esophagus as the electrically active region of the diaphragm (EARdi) and its center as the EARdi center. EMGdi signals were obtained via a multiple-array esophageal catheter consisting of seven sequential electrode pairs with three different electrode configurations. Subjects (n = 5) performed voluntary contractions of the diaphragm at functional residual capacity. Visual inspection of the signals revealed reversal of signal polarity on either side of the EARdi center. Extreme correlation values (r values close to -1 at 0-ms time offset) were observed for the correlation of signals on either side of the EARdi center. The root mean square (RMS) was reduced at the EARdi center; moving peripherally from the EARdi center (caudally and cephalad), the RMS increased to a peak (range of 2.1-4.1 dB for the different electrode configurations) and then decreased for the most peripheral electrode pairs. From a position where the RMS values peaked, center frequency values increased at the EARdi center (range of 26-29 Hz for the different electrode configurations). Computer simulation yielded similar data to the experimental results. We conclude that electrode positioning within the EARdi severely influences center frequency and RMS values and that the center of the EARdi can be identified via cross-correlation analysis.
Diaphragm↗
Chest wall muscle cross talk in canine costal diaphragm electromyogram.
The present paper describes the influence of cross talk from the abdominal and intercostal muscles on the canine diaphragm electromyogram (EMG). The diaphragm EMG was recorded with bipolar surface electrodes placed on the costal portion of the diaphragm (abdominal side), aligned in the fiber direction, and positioned in a region with a relatively low density of motor end plates. The results indicated that cross talk may occur in the diaphragm EMG, especially during conditions of loaded breathing and light general anesthesia. The cross-talk signals showed characteristics that were entirely different from the diaphragm EMG. Although the diaphragm EMG was typical for signals recorded with electrodes aligned in the fiber direction, the cross-talk signals were characteristic of those obtained with electrode pairs not aligned in the direction of the muscle fibers. Alterations in electrode positioning, interelectrode distance, and/or electrode surface area cannot guarantee the elimination of cross-talk signals, whereas spinal anesthesia at a high thoracic level will paralyze the sources of the cross talk and hence eliminate the cross-talk signals. By taking advantage of the differences in EMG signal characteristics for the diaphragm EMG and cross-talk signals, an index that has the capability to detect cross talk was developed.
Abdominal Muscles↗
Effects of muscle-to-electrode distance on the human diaphragm electromyogram.
It has been suggested that esophageal recordings of the diaphragm electromyogram (EMGdi) are influenced by changes in chest wall configuration. Whether the changes are of physiological or artifactual origin is unclear. For example, the distance between the esophageal electrode and the diaphragm is likely to alter with chest wall configuration and may lead to misinterpretations of EMGdi. The aims of this study were 1) to evaluate and quantify the effect of the muscle-to-electrode (ME) distance filter on EMGdi, as obtained with a multiple-array esophageal electrode, 2) to take advantage of the ME distance filter to locate the position of the diaphragm with respect to the electrode, and 3) to evaluate the influence of lung volume and chest wall configuration on EMGdi center frequency (CF) while controlling for the ME distance filter and signal quality. Five subjects performed six static contractions of the diaphragm at each of seven chest wall configurations, as evaluated by the method of K. Konno and J. Mead (J. Appl. Physiol. 22: 407-422, 1967). EMGdi was measured with seven pairs of electrodes mounted on an esophageal catheter. The pair of electrodes whose EMGdi power spectra were the least filtered by the ME distance was assumed to be closest to the diaphragm. The results of the study indicated that 1) EMGdi power spectra were strongly affected by the distance between the diaphragm and the electrodes. CF decreased by approximately 1 Hz/mm displacement away from the electrode pair closest to the diaphragm; and 2) no systematic relationship was found between changes in chest wall configuration and CF, when CF was measured from the electrode pair closest to the diaphragm. We conclude that the EMGdi CF can be reliably measured with a multiple-array esophageal electrode that covers the span of diaphragmatic excursion and by selecting the pair of electrodes that is the closest to the diaphragm.
Diaphragm↗
Ventilatory response to spontaneous resistive load variations during sleep.
We investigated the ventilatory response to spontaneous changes in resistive load during sleep in nine adult asthmatic patients, four of whom were snorers. All patients had a history of nocturnal worsening of respiratory symptoms and were submitted to a nocturnal polysomnographic study in a sleep laboratory. During the night, all patients showed spontaneous increases in pulmonary resistance due to bronchoconstriction. A temporary additional increase in inspiratory resistance (RI) was observed as a result of snoring. In all patients, a highly significant inverse linear relationship was found between ventilation (VE) and RI, but the slopes of the regressions varied considerably among patients; the decrease in VE was due to a reduced mean inspiratory flow. The most effective ventilatory compensation to increasing resistive load (lowest absolute values in the VE/RI slopes) was observed in two patients: one nonsnorer and one snorer. Effective VE compensation appeared to be dependent on the individual's combined adjustments of transpulmonary pressure (Ptp) and duty cycle (TI/TT). In fact, an increase in Ptp, linearly related to RI, was observed in all patients except one (a snorer during nonsnoring breathing); however, the Ptp increase was able to compensate VE only when TI/TT increased. We conclude that, in sleeping asthmatic patients, VE adaptation to increased spontaneous load is highly variable among patients and its effectiveness is related to individual strategies on the basis of adequate adjustments of neuromuscular output and timing of the breathing cycle.
Adult↗
An ATP-sensitive potassium channel blocker decreases diaphragmatic circulation in anesthetized dogs.
The goal of this study was to determine whether in the dog ATP-sensitive K+ channels blocked with glibenclamide affect diaphragmatic blood flow [phrenic arterial blood flow (Qpa)] during both spontaneous breathing at rest and increased diaphragmatic activity. A control group (no glibenclamide; n = 4) and an experimental group (50 mg/kg of glibenclamide; n = 5) were studied. During spontaneous breathing at rest, Qpa was 15.0 ml.min-1 x 100 g-1 and decreased by 5% in the presence of glibenclamide. Diaphragmatic pacing (30 min-1) generated by phrenic nerve pacing produced an initial diaphragmatic tension-time index of 0.25 in both groups. A 50% decay in transdiaphragmatic pressure was reached at 165 s in the experimental group compared with 421 s in the control group. Diaphragmatic pacing increased Qpa by 46% in the experimental group and 65% in the control group, yielding a 63% greater vascular resistance in the experimental group. Phrenic vein K+ content at rest was unchanged by the presence of glibenclamide, being 3.6 +/- 0.16 mmol/l compared with 3.5 +/- 0.19 mmol/l in the control group. Phrenic nerve pacing in the control group produced a 13% increase in phrenic vein K+ content, whereas in the experimental group a 16% decrease was observed. We suggest that ATP-sensitive K+ channels play an important role in the modulation of Qpa.
Adenosine Triphosphate↗