INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Although patients with tetraplegia contract the clavicular portion of the pectoralis major muscle to deflate the rib cage during forced expiration and during cough (1), their ability to raise intrathoracic pressure is markedly reduced. This reduction results from the paralysis of the abdominal and expiratory rib cage muscles and is such that in many patients, no dynamic compression of the intrathoracic airways occurs (4). Therefore, cough is ineffective and the clearance of airway secretions is markedly impaired.

Two strategies designed to augment the rise in intrathoracic pressure and achieve dynamic airway compression have been investigated. The first was based on the placement of a nonelastic strap around the abdomen so as to prevent the outward (paradoxical) displacement of the ventrolateral abdominal wall that occurs during forced expiration in most patients (2, 3). This procedure proved to be ineffective and did not produce any significant change in intrathoracic pressure (5). The second approach used electrical or magnetic stimulation of the abdominal muscles (6). The two studies in which pressures were actually measured, however, have provided conflicting results. Specifically, Linder (8) reported that stimulation during voluntary cough, compared with unassisted cough, causes substantial increases in maximum expiratory pressure at the mouth (MEP), whereas Lin and coworkers (9) did not observe any significant augmentation in MEP during stimulation applied at the end of a tidal inspiration. The potential therapeutic benefit of this strategy, therefore, remains unclear.

This prompted us to reinvestigate the effectiveness of magnetic stimulation of the abdominal muscles in a group of patients with chronic tetraplegia. We first measured the effects of the procedure on abdominal pressure during relaxation at various lung volumes; a group of matched healthy individuals was studied for comparison. We next examined the effects of the procedure on the rise in intrathoracic pressure during forced expiration in order to evaluate the potential occurrence of dynamic airway compression. Significant rises in abdominal and intrathoracic pressure were observed during stimulation, thus indicating that the chronically paralyzed muscles retain a definite force-generating ability. To understand this residual force, we assessed the thickness of the abdominal muscles.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Subjects

The study was performed in eight patients with tetraplegia and eight unaffected subjects matched for age, sex, height, and weight (Table 1). The patients had suffered accidental fracture-dislocation of the cervical spine between the fourth and seventh cervical vertebra and were studied 4 to 25 yr after injury. Completeness of the cord transection in each patient was established on the basis of a detailed neurological examination, which showed no detectable motor or sensory function below the level of injury. At the time of the studies, the patients were confined to wheelchairs and were in a clinical stable state with no respiratory symptoms. The control subjects were recruited from the hospital personnel; they were all nonsmokers, did not have any history of respiratory or neuromuscular disease, and had normal pulmonary function tests. The patients and control subjects were informed of the nature and extent of the investigation, and gave verbal consent to the procedures as approved by the Human Studies Committee of our institution.

Measurements

All measurements were carried out with the subject in the seated posture. After the restrictive garments were removed, functional residual capacity (FRC), vital capacity (VC), total lung capacity (TLC), and residual volume (RV) were determined in duplicate by the closed circuit helium dilution technique (model 2400; Sensormedics, Anaheim, CA). A conventional balloon-catheter system was then placed in the stomach to measure gastric pressure (Pga). The balloon was connected to a differential pressure transducer (Validyne, Northridge, CA) and filled with 1.0 ml of air; the air-filled system and the transducer, when tested by a square wave of 100 cm H₂O, responded with a time rise to 95% in < 50 ms. With the subject bending the trunk slightly forward and resting the forearms on the thighs, paired bilateral stimulation of the lower thoracic nerve roots was then performed. Stimuli were delivered with a 90-mm-diameter magnetic coil applied over the T10 spinal level and connected to a Magstim 250 stimulator (Magstim, Whitland, Dyfed, UK) (9). The interstimulus interval could be adjusted from 10 to 999 ms, which corresponded to a stimulation frequency of 100 to 1 Hz. All stimulations were applied during voluntary relaxation against a closed airway, with the subject wearing a noseclip.

Intensity profiles at FRC were first generated in each subject by using stimulation intensities between 20 and 100% of maximal stimulator output and a stimulation frequency of 30 Hz. Next, frequency profiles were generated while the stimulation intensity was maintained at 100% of maximal stimulator output. The frequencies were set at 20, 30, 40, 50, 75, and 100 Hz in the control subjects, while in the patients only frequencies of 30 and 100 Hz were used. The effect of lung volume was subsequently assessed. Thus, with the intensity and the frequency maintained at 100% and 30 Hz, respectively, stimulations were delivered at RV, midinspiratory capacity (FRC+), and TLC. To attain FRC+, the subjects were connected to a spirometer and instructed to breathe in to TLC and slowly expire until FRC+ was reached. Measurements were not obtained at RV in the patients because RV and FRC were quite similar owing to the marked reduction in expiratory reserve volume (ERV). At least three stimulations were performed in each condition.

When these measurements were completed, we assessed in each patient the effect of abdominal muscle stimulation on the pressures and expiratory flow rates (exp) during the course of a forced expiration. Because intrathoracic pressure, which is the driving pressure for flow, may be lower than Pga during such maneuvers, owing to the development of passive tension in the diaphragm (14), the gastric balloon was withdrawn to the lower third of the esophagus to record esophageal pressure (Pes). Flow was measured at the mouth with a heated Lilly-type pneumotachograph attached to a differential pressure transducer, and volume was obtained by digital integration of the flow signal. Calibration of flow was made with a calibrated rotameter (series 2000 variable area flowmeter; Si-Plan Electronics Research, Stratford upon Avon, UK); the response of the pneumotachograph was linear up to 700 L/min.

The patient first performed a series of two to four unassisted maximum expiratory VC maneuvers; the largest Pes achieved in these efforts was used as an index of expiratory muscle strength. Four to eight similar maneuvers were then obtained, during which the abdominal muscles were given a paired stimulation (frequency, 30 Hz; intensity, 100%). The lung volume at which the stimulation was delivered was selected by monitoring the flow-volume curve on an oscilloscope placed in front of the investigator. All signals were also recorded on a videotape recorder and an Olivetti PC (sample rate, 200 Hz).

In each patient and each control subject, we also measured the thickness of the rectus abdominis (RA), external oblique (EO), internal oblique (IO), and transversus abdominis (TA) muscles with the aid of a high-resolution 5-MHz ultrasound linear probe (Acuson 128 computed sonography system; Acuson, Mountain View, CA) (15). Measurements were obtained on the right side with the subject relaxing at FRC in the seated posture. For the EO, IO, and TA muscles measurements were made on the anterior axillary line, midway between the costal margin and the iliac crest; for the RA muscle, they were made 2-3 cm lateral to the umbilicus. Muscle thickness was measured with a built-in electronic caliper. All measurements were made in duplicate, and the average values were used for analysis.

Data Analysis and Conventions

For the stimulations during relaxation, gastric pressure was measured as the pressure difference between relaxation and the peak value; in each condition studied, the best value was taken for analysis. For the stimulations during forced expiration, we measured the changes in Pes and exp caused by stimulations delivered between 80 and 20% of the expiratory VC. Data are expressed as means ± SE. Statistical comparisons were made with t tests and ANOVA, when appropriate. A level of p < 0.05 was taken as significant.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Control Subjects

Figure 1 shows typical records of Pga obtained in a representative control subject (Figure 1A) during stimulation of the abdominal muscles at FRC, and Figure 2 summarizes the group values of Pga at all stimulation intensities. The magnitude of Pga increased with the stimulation intensity in all subjects (p < 0.001), such that with the intensity set at 100% of maximal output, it averaged 76.0 ± 11.7 cm H₂O. The Pga was also affected by lung volume, increasing to 88.9 ± 7.4 cm H₂O at TLC and decreasing to 59.6 ± 9.2 cm H₂O at RV (p < 0.001). On the other hand, with the intensity set at 100% of maximal output, Pga was independent of the stimulation frequency (30 Hz, 76.0 ± 11.7 cm H₂O; 100 Hz, 71.8 ± 10.9 cm H₂O). These results are in all respects similar to those previously reported in healthy subjects by Lin and colleagues (10) and Kyroussis and colleagues (12).

View larger version (64K): [in this window] [in a new window]   Figure 1.   Records of gastric pressure obtained in a representative control subject (A) and a patient with tetraplegia (B) during two consecutive stimulations (frequency, 30 Hz; intensity, 100%) of the abdominal muscles at FRC. Bars correspond to 10 cm H2O.

View larger version (15K): [in this window] [in a new window]   Figure 2.   Mean (± SE) changes in gastric pressure (Pga) elicited by paired stimulation (frequency, 30 Hz) of the abdominal muscles at FRC in eight patients with tetraplegia (closed circles) and eight matched unaffected subjects (open circles). Stimulation intensities were increased in each subject from 20 to 100% of maximal stimulator output.

Patients with Tetraplegia

All patients had a restrictive ventilatory impairment (Table 2). The VC and TLC were decreased to 66.1 and 82.3% of the predicted normal value (16), respectively, whereas RV was elevated in most patients. This elevation resulted from the reduced expiratory reserve volume (range, 0.17 to 1.23 L), and indeed all patients had severe expiratory muscle weakness with a maximum Pes during unassisted forced expiration of 19.2 ± 3.2 cm H₂O; in control subjects, Pes during forced expiration is at least 100-150 cm H₂O (17, 18).

The patients tolerated the procedure well and did not develop any involuntary muscle spasms in response to abdominal stimulation. As in the control subjects, stimulation induced a rise in Pga in each patient (Figure 1B), and the magnitude of the pressure rise increased with the stimulation intensity (Figure 2). However, the values achieved were substantially lower than those measured in the control subjects, and the difference was significant for all intensities above 60% of maximal stimulator output. Thus, with the stimulation intensity set at 100% of maximum, the mean Pga at FRC was 29.9 ± 3.7 cm H₂O (p = 0.002), and although this value increased to 43.0 ± 6.1 cm H₂O during stimulation at TLC (p < 0.002), it remained much lower than that recorded in the control group. The magnitude of Pga was not related to the time elapsed since the cord injury, and increasing the stimulation frequency from 30 Hz (29.9 ± 3.7 cm H₂O) to 100 Hz (27.8 ± 3.8 cm H₂O) did not introduce any significant change.

Twenty-five stimulations (2 to 4 per patient) were obtained between 80 and 20% of the expiratory VC and considered in the data analysis, and Figure 3 shows the tracings of Pes and exp versus lung volume in two representative patients. One stimulation was applied in each patient, after exhalation of 78% VC in patient 4 (Figure 3, left) and of 64% VC in patient 5 (Figure 3, right). In agreement with our previous observation (4), Pes increased rapidly at the beginning of the expiratory effort and then commonly decreased as expiration proceeded (Figure 3, top). However, the stimulation produced an abrupt rise in Pes in all patients, and in six of them this rise was consistently accompanied by a transient increase in exp in excess of the maximal flow attained during unassisted efforts (Figure 3, lower left). On the other hand, the rise in Pes in two patients (patients 5 and 3) did not result in any burst of flow. For all stimulations in the eight patients studied, the rise in Pes averaged 22.7 ± 4.5 cm H₂O; adding this value to that obtained at the same lung volume without stimulation yielded a mean value of 34.8 ± 4.9 cm H₂O. The corresponding net Pes value in the six patients who showed a flow transient during stimulation was 29.4 ± 4.6 cm H₂O, the average change in exp being 1.32 ± 1.0 L/s.

View larger version (24K): [in this window] [in a new window]   Figure 3.   Records of esophageal pressure (top) and expiratory flow rate (bottom) against lung volume during a forced expiratory vital capacity maneuver in two representative patients with tetraplegia. In each patient, the abdominal muscles were given one paired stimulation (frequency, 30 Hz; intensity, 100%) during the course of the maneuver. The stimulation produced an abrupt rise in pressure in both patients. However, an increase in flow in excess of the maximal flow attained during unassisted efforts was seen only in patient 4 (bottom left).

The values of abdominal muscle thickness measured in the control subjects and the patients are summarized in Table 3. Although the difference was not significant for the TA muscle, all muscles were thinner in the patients, such that the cumulated muscle thickness was reduced by 34% (p < 0.001). Muscle thickness was not related to the time postinjury but was significantly correlated with the Pga obtained during stimulation at FRC (p < 0.05) or TLC (p < 0.01); in other words, thicker abdominal muscles were associated with a greater Pga during stimulation (Figure 4).

View larger version (13K): [in this window] [in a new window]   Figure 4.   Relationship between the cumulated thickness of the abdominal muscles and the change in gastric pressure (Pga) obtained during paired stimulation (frequency, 30 Hz; intensity, 100%) of the abdominal muscles at TLC. Closed circles, patients with tetraplegia; open circles, control subjects.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Previous studies on a number of limb muscles have clearly established that the strength of the chronically paralyzed muscles is reduced in patients with tetraplegia. For example, maximal strength of the triceps brachii muscle in such patients, as assessed by electrical stimulation, is only 18% of that in unaffected control subjects (19). Other studies have reported a 30- 35% reduction in the maximal strength of the soleus (20) and thenar muscles (21). Therefore, even though different muscles may have different degrees of muscle weakness, the 60% decrease in abdominal muscle strength found in this study lies well within the range reported for limb muscles.

The weakness of limb muscles in patients with tetraplegia is primarily related to muscle fiber atrophy. Indeed, biopsies of the vastus lateralis muscle performed 6 and 24 wk after injury in patients with complete spinal cord transection have shown a 35% decrease in average fiber cross-sectional area (22). Studies using magnetic resonance imaging have also shown that the leg and thigh muscles in such patients have a 20 to 55% decrease in cross-sectional area (23). In agreement with these findings, our patients had a 34% decrease in abdominal muscle thickness. The additional observation that muscle thickness correlated well with muscle strength (Figure 4) also supports the contention that in these patients, muscle atrophy is the primary determinant of muscle weakness.

Our estimates of the degree of abdominal muscle strength and thickness might be approximate for two reasons. First, paired stimuli as used in the current study are not expected to produce maximal forces, and indeed, although Pga increased with increasing stimulation intensity in both the control subjects and the patients, pressure did not achieve any plateau (Figure 2). This indicates that the muscles were not maximally activated. However, a study of the effects of magnetic stimulation of the abdominal muscles in unaffected subjects has shown that MEP increased by only 86.5 ± 13.5 cm H₂O when trains of stimuli (frequency, 20 Hz; intensity, 70% of maximum) were applied for 2 s at the end of a tidal inspiration; yet, with the stimulus intensity set between 70 and 90% of maximum, a plateau of pressure was achieved (10). This value is similar to that found in our control group, and this suggests that our stimulations at 100% intensity were not far from producing maximal muscle activation.

The second reason for which the present estimate of abdominal muscle weakness may be approximate is related to the fact that most patients with tetraplegia have a protuberant abdominal wall when seated. This should lengthen the abdominal muscles and result in a reduction in muscle thickness and an increase in muscle force. Abdominal muscle length in dogs, however, increases by less than 15% during passive inflation from FRC to TLC (24), and it is likely that the effect of abdominal protuberance on muscle length is even smaller. Therefore, the degree of abdominal muscle weakness may have been underestimated in our patients, but the magnitude of this error was probably small.

The degree of abdominal muscle weakness observed in our patients appears to be greater than in the study of Linder (8), who reported in eight patients with chronic tetraplegia a mean MEP of 60.0 cm H₂O during cough assisted by abdominal stimulation. Lin and coworkers (9) also found an MEP of 66.4 cm H₂O in 13 patients with tetraplegia during abdominal muscle stimulation at the end of a tidal inspiration. Several factors related to the study protocols may account for this difference. First, Linder (8) superimposed the stimulations on forceful coughing efforts; the pressures measured therefore reflected contraction of both the rib cage and abdominal expiratory muscles. Second, the stimulations in both the study by Linder (8) and that by Lin and coworkers (9) were applied at volumes greater than FRC, and the current measurements have clearly confirmed the influence of lung volume on the pressure-generating ability of the abdominal muscles. Finally, the possibility exists that some of the patients studied by these investigators had incomplete cord transection and residual abdominal muscle function. Although we cannot demonstrate this at this stage, the values of MEP and ERV in these patients averaged 50-70% of the predicted normal values (9), whereas the values usually reported in patients with complete cervical cord transection (2, 5, 25) range between only 30 and 50% of predicted. Partial preservation of abdominal motor innervation in the patients of Lin and coworkers (9) could also explain the lack of significant difference between the MEP generated during spontaneous efforts and those measured during abdominal stimulation.

The eight patients of this study had complete spinal cord transection, yet abdominal muscle stimulation in two of them did not result in any burst of flow in excess of that achieved during unassisted expiratory efforts (Figure 3, lower right). This observation confirms the prominent role played by the rib cage muscles in the process of active expiration by patients with tetraplegia (1) and provides further evidence that contraction of these muscles may be sufficient to cause dynamic airway compression and expiratory flow limitation (4). In the other six patients, stimulation of the abdominal muscles elicited transient increases in both intrathoracic pressure and expiratory flow (Figure 3, left), thus indicating that dynamic airway compression was not achieved during unassisted efforts. However, the most important result of the present studies is that the net peak pressure achieved during stimulated efforts averaged 29.4 cm H₂O, and was therefore higher than the value of 10-15 cm H₂O required to initiate dynamic airway compression (4, 5, 26). By enhancing or producing dynamic airway compression, magnetic stimulation of the abdominal muscles might therefore improve the clearing of airway secretions in patients with tetraplegia. As a corollary, abdominal stimulation applied at regular intervals could be useful in reducing the prevalence and severity of respiratory infections.