A non-volitional skeletal muscle endurance test measures functional changes associated with impaired blood flow

Introduction

Mechanomyography (MMG) is a non-invasive measurement of the oscillations produced by surface skeletal muscles during contraction. Previous research has identified a strong correlation between declines in maximum peak-to-peak MMG amplitude and peak torque during stimulated fatigue in limb muscle. ¹ It was thus proposed that reductions in surface MMG during fatigue could reflect depressed Ca²⁺ transients in fatigued fibers that coincide with lower capability to generate force muscle. ¹ Further research has confirmed that MMG is an accurate and reliable methodology in estimating skeletal muscle function in both the contracted and relaxed state.^2–5

A muscle fatigue test was proposed in 2017 that assesses muscle twitch responses to a submaximal, constant current, electrical stimulation measured by mechanomyography. ⁶ The proposed test measures maximum peak-to-peak MMG amplitude (i.e., contraction magnitude) over the range of stimulation frequencies a clinical electrical stimulator can achieve that are still low enough to avoid fusing of the action potentials.^6,7 Submaximal, non-tetanic contractions are chosen because tetanic, higher force contractions may have immediate adverse effects in clinical populations such as orthopedic injury, ⁸ exercise-induce muscle injury, ⁹ occluded blood flow, ¹⁰ and reduced tolerability. ¹¹ The developers of this test have provided evidence that MMG provides a good proxy for torque over a single muscle twitch, ⁶ but the procedures should be examined to ensure they provide a valid measure of muscle function over the proposed intermittent fatigue test in muscles that are accessible in patients confined to a hospital bed. Patients confined to hospital beds experience reductions in weight-bearing activity due to immobilization consequently leading to decreases in skeletal muscle strength, size, and function. ¹² Intensive care unit acquired weakness (ICUAW) is associated with prolonged periods of recovery and a decreased quality of life ¹³ and as many as eighty percent of patients with ICUAW have functional impairments for up to 5 years after discharge. ¹⁴ Early diagnosis is thought to be crucial in the treatment of ICUAW.^15–17 Measuring changes in muscle function and joint torque through dynamometry is not a practical method in many clinical settings due to cost, spacing and resources. Traditional dynamometers are not portable, requiring a dedicated lab space for testing. This would require physically moving patient to a separate lab for strength assessments. In addition, multi-joint dynamometers generally cost tens of thousands of dollars per unit. Handheld dynamometry may overcome the cost and portability constraints for strength testing, but the proposed procedures using dynamometry still require the subject to voluntarily perform maximal contractions.^18–20 However, MMG measured through surface accelerometers could allow clinicians to evaluate skeletal muscle function via stimulation while patients are restricted to a hospital bed regardless of their level of consciousness. While the proposed procedures would allow us to assess skeletal muscle in these patients, the previous studies published using this test have not compared muscles between a state of high and low function.^6,21,22 More evidence is needed to confirm whether the aforementioned submaximal fatigue protocol can detect clinically relevant changes in muscle function when they should be present. A clinically relevant change would be of sufficient magnitude to cause disability, from either weakness or fatigue. ²³

It is well established that ischemic environments increase rates of fatigue,^24–30 and that MMG can be used to measure skeletal muscle fatigue.^31–38 If the proposed fatigue protocol is valid, it should be able to detect an increase in fatigue when the muscle is manipulated into an ischemic environment. Fatigue in this study is defined as a reduction in MMG amplitude from the peak-to-peak contraction amplitude observed over the entire stimulation period. We refer to this as a reduction in contraction magnitude. Inducing an ischemic environment should induce a clinically relevant decrease in skeletal muscle function because impaired blood flow is associated with clinical weakness ³⁹ and increased fatiguability. ⁴⁰ Healthy subjects were used in this study because there were concerns whether tourniquet use in clinical populations might elevate the risk for thrombosis. ⁴¹ Therefore, the purpose of this study was to provide evidence of validity for the proposed fatigue test procedures in the ankle dorsiflexor and wrist extensor muscles. This was achieved by first demonstrating that the acceleration measurements provided a valid approximation of force throughout each stimulation phase, and then determining whether data from the proposed fatigue protocol can detect reduced function in the ankle dorsiflexors and wrist extensors in response to occluded blood flow. The first hypothesis was torque would highly correlate with MMG measures. The second hypothesis was mean contraction magnitude would be demonstrably lower when the tourniquet was applied proximal to the target muscle since weakness and fatiguability are rapidly brought on by blood flow occlusion. The third hypothesis was that there would be differences in the magnitude of fatigue between muscle groups at different stage of the protocol.

Methods

Subjects

This study was reviewed and approved by the Georgia State University Institutional Review Board (IRB #: H18601). Subjects were recruited from the Georgia State University student body. All subjects provided written informed consent. Based on a health history form, subjects who failed to meet the American College of Sports Medicine (ACSM) guidelines for low risk were excluded from participation. ⁴² Table 1 provides a summary of subject characteristics.

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Table 1.

Subject characteristics.

	Experiment 1 (n = 6)	Experiment 2 (n = 10)
Gender (m, f)	5, 1	8, 2
Age	29.5 ± 6.3	33.6 ± 8.4
Height (m)	1.74 ± 0.14	1.79 ± 0.12
Weight (kg)	79.3 ± 14.6	83.5 ± 20.1
Body mass index [BMI] (kg/m2)	26.1 ± 2.7	25.8 ± 3.3

All values reported as mean ± SD.

Results

Discussion

The results from this study show that the mean contraction magnitude measured by MMG was strongly related to torque over the three stimulation frequencies. These results are in line with previous studies showing a strong relationship between torque and MMG in other muscle groups.^6,37,43,44 It is important to note that this correlation was found using values normalized to the peak contraction magnitude for both acceleration and torque respectively. This was done because the researchers wanted to remove differences in individual anatomy, such as leg length, that change the moment arm or angle of the joint and therefore torque. ⁴⁵ In addition, due to the use of federally approved clinical devices that would be used in a hospital setting, we were unable to match the force and acceleration profiles of every individual muscle contraction. The U.S. Food and Drug Administration’s Guidance Document for Powered Muscle Stimulators limits the maximum power density of these devices to 0.25 W/cm² based on the smallest electrode size available (Section 3 notes, paragraph 6, 1999). There was a limited ability to regress acceleration and torque values from the individual contractions produced during the protocol. Therefore, a mean contraction magnitude and torque over each stimulated frequency period was used to compare across all subjects in the first experiment. This first experiment provides some evidence that MMG data provides a valid approximation of skeletal muscle torque and/or the degree of weakness throughout the proposed constant current, intermittent fatigue protocol, but these results should be interpreted with caution since the sample size is small (n = 6).

In the second experiment, applying a tourniquet above the elbow resulted in significantly reduced contraction magnitudes for the 4 Hz, and 6 Hz stimulation periods compared to the control trial. A tourniquet applied above the knee resulted in overall reductions in contraction magnitude throughout the trial. Overall, the application of the tourniquet impaired submaximal evoked contractions. Prior to this study, we questioned whether our data would show any differences in muscle performance because the protocol used submaximal stimulations. These results suggest that the proposed assessment procedure could detect impaired muscle performance due to impaired blood flow. While we do not have measurements of maximal voluntary contractions to confirm the presence of fatigue, previous research indicates that occluding blood flow results in enhanced fatigue,^{24,25,27–30,46–48} and have also found that impairing blood flow results in enhanced fatigue during electrically induced contractions as evidence of fatigue intrinsic to the stimulated muscles.^46,47 In light of these previous findings in combination with research that shows strong relationship between MMG amplitude and produced torque across various contraction types,^49–52 we interpret the reduced evoked contraction magnitudes associated with the application of the tourniquet as a measurement of impaired muscle function resulting from fatigue stemming from occlusion. This supports previous findings which have shown that blood flow occlusion during exercise results in lower stimulated doublet force than just exercise alone. ⁴⁶ The current study provides the first evidence that the proposed test can detect a functional change in skeletal muscle using MMG. The authors believe that confirming the validity of these assessments in a healthy population during periods of altered skeletal muscle function supports further investigation of the stimulated fatigue assessments in ICU patients. The proposed methods have potential to be a convenient and less expensive clinical test to assess skeletal muscle function throughout an ICU visit. Accelerometry data collected during stimulated assessments could be used to identify muscle weakness when it is present and determine if therapies are sufficiently improving patient outcomes. This further research in the clinical population is warranted before developing guidelines for assessment.

Prior studies have reported on differences between muscle groups using this fatigue protocol. Willingham & McCully compared carpal flexor fatigue indices against gastrocnemius fatigue indices, finding significantly greater fatigue in the forearm. ⁶ The present study found the non-occluded ankle dorsiflexor produced lower contraction magnitudes across all three stages of the fatigue protocol compared to the non-occluded wrist extensor contractions. These differences persisted after occluding the blood flow, but by the 6 Hz stimulation period the differences were no longer significant. A potential explanation for this finding could be due to the fiber type composition of the two observed muscle groups. Fiber type composition has been previously proposed to explain differences in MMG amplitude and mean power frequency between resistance trained and aerobically trained men during a fatigue protocol. ⁵³ Research has shown high Type II fiber distribution in human tibialis anterior ⁵⁴ while human digital and wrist extensor muscles have a relatively higher distribution of MHC I content. ⁵⁵ In the current study, this may explain a more immediate onset of contraction magnitude depression in the occluded AD, where declines in contraction magnitudes of the occluded WE were more prevalent compared to control during in the second and third stages (i.e., 4 and 6 Hz). Given that this last stage (i.e., 6 Hz) occurred at approximately 6 minutes into the protocol, in combination with occlusion, it is likely that at this point there was a rapid onset of fatigue in lower threshold fibers of the wrist extensors. By the third stage during occlusion contraction magnitudes were not significantly different between the ankle dorsiflexors and wrist extensors. This demonstrates that the protocol can detect differences in occlusion-promoted contraction magnitude and therefore fatigue across skeletal muscles with varying characteristics (e.g., fiber type distribution). Future research would benefit from the use of muscle biopsy to evaluate the influence of fiber type composition on occlusion-induced stimulated fatigue response in clinical populations. It has been demonstrated that long periods of bed rest lead to a mismatched expression and production of MHC isoforms and a shift towards the Type II phenotype.^56,57 Future research should determine how fiber type composition may influence fatigue during periods of occlusion in the clinical bedridden population.

The results showed no effect from the trial order on the average contraction magnitude. This confirms that any effects observed were due to the application of the tourniquet and not from any carryover fatigue from the previous trials. While it is possible the subjects may not have fully recovered in the 10 min between trials, this does not appear to have significantly affected the results.

Limitations

The low sample size and population during the torque and MMG measurements limits our ability to generalize these findings to clinical populations. Future research should collect torque and MMG data using this protocol to confirm these findings. The absence of maximal voluntary contractions during the tourniquet experiment limit our ability to confirm that fatigue was present in the entire muscle during the second experiment. This limits the ability to assess whether changes observed throughout the stimulation protocol reflect the total force production capability of the muscle or just a deficit present in the stimulated muscle fibers. Therefore, we interpret our findings to mean a functional deficit was detected within the fibers activated during the electrical stimulation protocol.

Previous research has suggested that increased subcutaneous fat can reduce MMG amplitude during both voluntary and non-voluntary contractions.^58–60 This study recruited individuals who met the ACSM classification for low risk, to minimize any risks associated with tourniquet use. This may have had an unintended consequence of creating a subject pool with a more uniform distribution and lower overall subcutaneous fat than that of a clinical population. It is possible that differences in subcutaneous fat between the experimental muscle groups could have influenced MMG contraction magnitude during the assessment. Skinfold data for these sites were not recorded to test this limitation nor are the authors aware of previous research that has statistically compared skinfold differences in the forearm and tibia to determine the impact on stimulated torque or accelerometry reading. However, it should be noted that the use of a normalized contraction magnitude was used to compare the wrist extensors and ankle dorsiflexors which minimizes the effects of non-muscular physiological differences.

Conclusion

Data from this study indicate that an accelerometer measured muscle fatigue protocol using submaximal stimulation intensities is capable of detecting differences in muscle function between occluded and normal blood flow states in a healthy population. This could mean the proposed muscle test would be able to distinguish a clinically relevant change in muscle quality, but more research is needed to determine this. Based on the data it may be necessary to examine clinical data in a variety of reporting schemas to determine the best interpretation of test results. The use of these assessments would allow for evaluation of skeletal muscle function throughout a patient’s stay in order to evaluate the effects of therapies on ICU acquired weakness. Further research is needed to evaluate the use of the proposed stimulated fatigue test to identify ICUAW on bed-ridden ICU patients.