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Bicycle exercise training improves ambulation in patients with peripheral artery disease

Open AccessPublished:September 05, 2019DOI:https://doi.org/10.1016/j.jvs.2019.06.188

      Abstract

      Objective

      Exercise training has multiple beneficial effects in patients with arteriosclerotic diseases; however, the exact underlying mechanisms of the effects are not completely understood. This study aimed to evaluate the effectiveness of a supervised exercise program in improving gait parameters, including the variability and walking performance of lower limb movements, in patients with peripheral artery disease (PAD) and intermittent claudication (IC).

      Methods

      Sixteen patients with a history of PAD and IC were recruited for this study, and they completed a 3-month supervised bicycle exercise program. The ankle-brachial index and responses to quality of life (QOL) questionnaires were evaluated. Near-infrared spectroscopy was also performed to determine the hemoglobin oxygen saturation in the calf. Patients' kinematics and dynamics, including joint range of motion and muscle tension, were evaluated using an optical motion capture system. Computed tomography images of each muscle were assessed by manual outlining. Data were collected before and after the supervised bicycle exercise program, and differences were analyzed.

      Results

      Significant differences were not found in step length, ankle-brachial index, and hemoglobin oxygen saturation before and after the supervised bicycle exercise program; however, IC distance (P = .034), maximum walking distance (P = .006), and all QOL questionnaire scores (P < .001) showed significant improvement. Hip range of motion (P = .035), maximum hip joint torque (right, P = .031; left, P = .044), maximum tension of the gluteus maximus muscle (right, P = .044; left, P = .042), and maximum hip joint work (right, P = .048; left, P = .043) also significantly decreased bilaterally. Computed tomography images showed a significant increase in the cross-sectional area of the abdominal, trunk, and thigh muscles but not in that of the lower leg muscles after the supervised exercise program intervention.

      Conclusions

      In this study, bicycle exercise training improved the QOL and walking distance and decreased hip movement. The results showed that bicycling might be as useful as walking in patients with PAD.

      Keywords

      Article Highlights
      • Type of Research: Single-center prospective cohort study
      • Key Findings: No significant differences were noted in step length, ankle-brachial index, and oxygen saturation before and after a 3-month supervised exercise program in 16 patients with claudication. On the contrary, intermittent claudication distance, maximum walking distance, and quality of life questionnaire scores showed significant improvement after the exercise intervention.
      • Take Home Message: Bicycle exercise training improved the quality of life and walking distance; less hip movement was found in patients with peripheral artery disease.
      Intermittent claudication (IC) is one of the symptoms of peripheral artery disease (PAD) that could disturb daily activities and athletic performance. Treatment of IC includes medication, surgical intervention, and exercise training. Among them, exercise training is less invasive, inexpensive, and recognized as the first-line therapy for IC.
      The effects of exercise training on PAD patients have been previously studied. Meta-analyses of randomized trials reported that walking distance increases >100% after exercise training.
      • Gardner A.W.
      • Poehlman E.T.
      Exercise rehabilitation programs for the treatment of claudication pain. A meta-analysis.
      • Robeer G.G.
      • Brandsma J.W.
      • van den Heuvel S.P.
      • Smit B.
      • Oostendorp R.A.
      • Wittens C.H.
      Exercise therapy for intermittent claudication: a review of the quality of randomised clinical trials and evaluation of predictive factors.
      Moreover, exercise training leads to significant improvements in walking performance, physical activity, and perceived quality of life (QOL) in patients with PAD and IC.
      • Gardner A.W.
      • Montgomery P.S.
      • Flinn W.R.
      • Katzel L.I.
      The effect of exercise intensity on the response to exercise rehabilitation in patients with intermittent claudication.
      The potential mechanisms for this improvement are explained by various factors, namely, collateral circulation,
      • Nicholson C.D.
      • Angersbach D.
      • Wilke R.
      The effect of physical training on rat calf muscle, oxygen tension, blood flow, metabolism and function in an animal model of chronic occlusive peripheral vascular disease.
      • Weiss T.
      • Fujita Y.
      • Kreimeier U.
      • Messmer K.
      Effect of intensive walking exercise on skeletal muscle blood flow in intermittent claudication.
      • Yang H.T.
      • Dinn R.F.
      • Terjung R.L.
      Training increases muscle blood flow in rats with peripheral arterial insufficiency.
      endothelial function,
      • Lloyd P.G.
      • Yang H.T.
      • Terjung R.L.
      Arteriogenesis and angiogenesis in rat ischemic hindlimb: role of nitric oxide.
      • Niebauer J.
      • Cooke J.P.
      Cardiovascular effects of exercise: role of endothelial shear stress.
      muscle metabolism,
      • Terjung R.L.
      • Mathien G.M.
      • Erney T.P.
      • Ogilvie R.W.
      Peripheral adaptations to low blood flow in muscle during exercise.
      • Hiatt W.R.
      • Regensteiner J.G.
      • Hargarten M.E.
      • Wolfel E.E.
      • Brass E.P.
      Benefit of exercise conditioning for patients with peripheral arterial disease.
      • Hiatt W.R.
      • Regensteiner J.G.
      • Wolfel E.E.
      • Carry M.R.
      • Brass E.P.
      Effect of exercise training on skeletal muscle histology and metabolism in peripheral arterial disease.
      hemorheology,
      • Capecchi P.L.
      • Pasini F.L.
      • Cati G.
      • Colafati M.
      • Acciavatti A.
      • Ceccatelli L.
      • et al.
      Experimental model of short-time exercise-induced preconditioning in POAD patients.
      • Ernst E.E.
      • Matrai A.
      Intermittent claudication, exercise, and blood rheology.
      walking economy,
      • Hiatt W.R.
      • Regensteiner J.G.
      • Hargarten M.E.
      • Wolfel E.E.
      • Brass E.P.
      Benefit of exercise conditioning for patients with peripheral arterial disease.
      • Hiatt W.R.
      • Wolfel E.E.
      • Meier R.H.
      • Regensteiner J.G.
      Superiority of treadmill walking exercise versus strength training for patients with peripheral arterial disease. Implications for the mechanism of the training response.
      • Womack C.J.
      • Sieminski D.J.
      • Katzel L.I.
      • Yataco A.
      • Gardner A.W.
      Improved walking economy in patients with peripheral arterial occlusive disease.
      and inflammatory responses.
      • Edwards A.T.
      • Blann A.D.
      • Suarez-Mendez V.J.
      • Lardi A.M.
      • McCollum C.N.
      Systemic responses in patients with intermittent claudication after treadmill exercise.
      • Khaira H.S.
      • Maxwell S.R.
      • Shearman C.P.
      Antioxidant consumption during exercise in intermittent claudication.
      • Tisi P.V.
      • Hulse M.
      • Chulakadabba A.
      • Gosling P.
      • Shearman C.P.
      Exercise training for intermittent claudication: does it adversely affect biochemical markers of the exercise-induced inflammatory response?.
      Several studies have reported an association between vascular function and structure in the process of exercise training, which has been well reviewed by Green et al.
      • Green D.J.
      • Hopman M.T.
      • Padilla J.
      • Laughlin M.H.
      • Thijssen D.H.
      Vascular adaptation to exercise in humans: role of hemodynamic stimuli.
      The quality and quantity of gait muscles are other contributing factors to the improvement of walking ability. The mechanisms of impaired muscle strength in PAD patients have not yet been clarified. As study hypothesis, gait muscles and relevant joint movement might be affected after the exercise training, which would contribute to improvements in walking ability.
      An efficient computational algorithm for multibody systems was previously developed and applied to the musculoskeletal model of the human body.
      • Nakamura Y.
      • Yamane K.
      • Fujita Y.
      • Suzuki I.
      Somatosensory computation for man-machine interface LE from motion-capture data and musculoskeletal human model.
      It was assumed that the inverse dynamics method, which is a method for computing forces and moments of forces (torques) based on kinematics, and the computation of a musculoskeletal human model using motion capture data would aid in elucidating the mechanisms underlying PAD improvements after exercise training.
      This study aimed to examine the effects of a 3-month supervised exercise program (SEP) on lower limb and trunk movement variability in IC patients and to evaluate lower extremity kinematics and muscle morphology before and after the SEP intervention.

      Methods

       Participants

      All patients who attended an outpatient clinic of a vascular surgery unit in Tokyo, Japan, between January 2013 and December 2015 were screened for the study. Patients were diagnosed as having PAD according to their history of claudication and if they had an ankle-brachial index (ABI) <0.9. Patients with critical limb ischemia (rest pain or tissue loss), history of ischemic heart disease or cerebral infarction, neurologic or musculoskeletal disorders, and dementia and those aged >80 years with limited gait and balancing ability were excluded. Near-infrared spectroscopy (NIRS) is useful for evaluating the function of the extremities in PAD patients.
      • Komiyama T.
      • Shigematsu H.
      • Yasuhara H.
      • Muto T.
      Near-infrared spectroscopy grades the severity of intermittent claudication in diabetics more accurately than ankle pressure measurement.
      • Vardi M.
      • Nini A.
      Near-infrared spectroscopy for evaluation of peripheral vascular disease. A systematic review of literature.
      It is not an invasive modality, and it was used routinely for claudicants in this study. A key parameter of NIRS is the recovery time of oxygenated and deoxygenated hemoglobin from the end of the walk to baseline. Recovery time was reported to be correlated with the severity of IC.
      • Komiyama T.
      • Shigematsu H.
      • Yasuhara H.
      • Muto T.
      Near-infrared spectroscopy grades the severity of intermittent claudication in diabetics more accurately than ankle pressure measurement.
      Calf muscle hemoglobin oxygen saturation (So2) was also shown in NIRS, and it primarily reflects the relative balance between oxygen delivery and oxygen utilization of local tissue.
      • Gardner A.W.
      • Parker D.E.
      • Webb N.
      • Montgomery P.S.
      • Scott K.J.
      • Blevins S.M.
      Calf muscle hemoglobin oxygen saturation characteristics and exercise performance in patients with intermittent claudication.
      In this study, to evaluate ischemic changes in calf muscles, differences in So2 before and after SEP intervention were compared.
      Computed tomography (CT) angiography (Aquilion; Toshiba, Tokyo, Japan) was performed in all participants for analysis of disease anatomy and mass. The transverse CT image of the lower border of the third lumbar vertebra was assessed in each patient. The rectus abdominis, abdominal oblique, psoas major, and erector spinae muscles were evaluated as previously described.
      • Harimoto N.
      • Shirabe K.
      • Yamashita Y.I.
      • Ikegami T.
      • Yoshizumi T.
      • Soejima Y.
      • et al.
      Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma.
      • Matsubara Y.
      • Matsumoto T.
      • Aoyagi Y.
      • Tanaka S.
      • Okadome J.
      • Morisaki K.
      • et al.
      Sarcopenia is a prognostic factor for overall survival in patients with critical limb ischemia.
      The transverse CT image of the lower end of the ischial bone and middle of the fibula was assessed in each patient to analyze the rectus femoris, gluteus maximus, and lower leg muscles. Cross-sectional areas of each muscle were measured by manually outlining the CT images using software (Aquarius iNtuition; TeraRecon, Tokyo, Japan; Fig 1). The field range of the cross section was determined through discussion between M.K. and K.H.; thereafter, M.K. measured the field. ABI, NIRS, and CT angiography were performed before and after the SEP intervention.
      Figure thumbnail gr1
      Fig 1Gait data were processed using a software program to determine the position of markers. The musculoskeletal model was applied to analyze the kinematics and dynamics of each motion. EMG, Electromyography; PC, personal computer.
      All patients provided written informed consent. The protocol was approved by the institutional Research Ethics Committee of The University of Tokyo Hospital (No. 10208-(2)).

       Exercise program protocol

      All enrolled participants underwent a 3-month SEP conducted in the vascular unit of our hospital and performed using a bicycle ergometer (Aerobike 900U; Konami, Tokyo, Japan). A bicycle ergometer in the cardiac rehabilitation program was used, in which a treadmill was not included. The program consisted of a bicycling exercise 3 days per week. Exercise intensity was set at 70% of maximal load with 30 minutes per session. The exercise protocol also incorporated warm-up and cool-down sessions that involved stretches of the major lower limb muscle groups (total exercise time, 40-60 minutes).

       Data acquisition and procedures

      Twelve cameras (Raptor-4, Eagle; Motion Analysis, Santa Rosa, Calif) were used to collect the kinematic and kinetic data of patients during continuous walking on a treadmill (Daikou DK-8421B; Kobe Medicare, Kobe, Japan). Participants wore comfortable clothes and shoes for testing. Thirty-five markers were set on the body surface to capture the kinematic data (Fig 2). The participants were instructed to walk continuously on the treadmill at a speed of 2.4 or 3.6 km/h until they could not continue because of exhaustion or pain, and they were instructed to inform the investigator when claudication symptoms developed. At this point, three outcomes (step length, distance until IC, and maximum walking distance) were recorded. These data were collected before and after the SEP intervention at the laboratory of our institution where the treadmill was available for use. These features were not analyzed with structured walking because kinematic data could be accurately collected by walking on the treadmill at the same speed.
      Figure thumbnail gr2
      Fig 2Computed tomography (CT) showing the area of skeletal muscle in each region (gray). The abdominal rectus muscle, abdominal oblique muscle, psoas major muscle, erector spinae muscle, rectus femoris muscle, gluteus muscle, and calf muscles were analyzed.

       QOL scores

      QOL before and after the exercise program was evaluated with two QOL measures. Walking distance, walking speed, and stair climbing were reported as three domains of the Walking Impairment Questionnaire, a PAD-specific measure of self-reported limitations.
      • Nicolai S.P.
      • Kruidenier L.M.
      • Rouwet E.V.
      • Graffius K.
      • Prins M.H.
      • Teijink J.A.
      The walking impairment questionnaire: an effective tool to assess the effect of treatment in patients with intermittent claudication.
      Each domain is scored on a scale of 0 to 100 points, wherein 0 represents extreme limitation and 100 represents no difficulty in walking long distances, walking rapidly, or climbing three flights of stairs.
      • Nicolai S.P.
      • Kruidenier L.M.
      • Rouwet E.V.
      • Graffius K.
      • Prins M.H.
      • Teijink J.A.
      The walking impairment questionnaire: an effective tool to assess the effect of treatment in patients with intermittent claudication.
      The Vascular Quality of Life questionnaire is a disease-specific measure of QOL specifically developed for assessing PAD patients and is also sensitive to within-patient changes.
      • Mehta T.
      • Venkata Subramaniam A.
      • Chetter I.
      • McCollum P.
      Assessing the validity and responsiveness of disease-specific quality of life instruments in intermittent claudication.
      • Morgan M.B.
      • Crayford T.
      • Murrin B.
      • Fraser S.C.
      Developing the Vascular Quality of Life Questionnaire: a new disease-specific quality of life measure for use in lower limb ischemia.

       Motion capture data analysis

      Gait characteristics were identified using kinematic and kinetic data as previously described. A visual three-dimensional motion analysis software was used (Cortex; Motion Analysis) to determine the sequence of the three-dimensional positions for the markers. A musculoskeletal model was applied to analyze the kinematics and dynamics of each patient's motion
      • Nakamura Y.
      • Yamane K.
      • Fujita Y.
      • Suzuki I.
      Somatosensory computation for man-machine interface LE from motion-capture data and musculoskeletal human model.
      (Fig 2). Inverse kinematics computation with the kinematic properties determined the joint angle sequence. The measured joints were the hip, knee, and ankle. The maximum range of motion (ROM) of each joint angle was analyzed. Inverse dynamic computation and the inertial properties of each patient were used to compute the generated forces, which correspond to the joint torques. Mathematical optimization was carried out to distribute the joint angles to the joint torques and then to the muscle maximum tensions. The evaluation function of inverse kinematics analysis and inverse dynamics analysis were used to calculate the optimum joint angle and force. Joint torques were analyzed by integrating the average of one cycle. All data were normalized to a 1.0 gait cycle. Motion capture data were collected before and after the SEP.

       Statistics

      Statistical analysis was performed using JMP Pro software (version 11.2.1; SAS Institute, Cary, NC). Categorical variables were expressed as numbers and percentages, and continuous variables were expressed as mean ± standard deviation or standard error. Group differences were evaluated using the paired t-test for continuous variables with JMP Pro software. Statistical significance was defined as P < .05.

      Results

      Nineteen IC patients were recruited for this study. Three patients were excluded from the analysis because of worsened IC, brain infarction, and intolerance of the SEP. A summary of the patients' (n = 16) characteristics is shown in Table I. IC symptoms appeared on the lower leg of 11 patients and on the whole lower extremity of five patients. The occlusion or stenosis was located on the aortoiliac region in six patients and on the superficial femoral artery-popliteal region in 10 patients. Six patients had bilateral lesions.
      Table ICharacteristics of the study participants
      PAD patients (n = 16)
      Age, years71.4 ± 6.0
      Sex, male:female13:3
      BMI, kg/m223.2 ± 3.1
      Ex-smoker8 (50)
      Anatomic division
       Aortoiliac6 (37.5)
       SFA-popliteal10 (62.5)
      Location of IC, right:left9:7
      Rutherford I16 (100)
      Diseases
       Hypertension12 (75)
       Hyperlipidemia9 (56)
       Diabetes mellitus12 (75)
       Ischemic cardiac disease4 (25)
       Cerebrovascular disease1 (6.2)
       Spinal stenosis3 (18)
      Medication
       Antiplatelet agent16 (100)
       Statin8 (50)
       Beta inhibitor4 (25)
       ACE inhibitor2 (12)
       ARBs9 (56)
       Calcium antagonist7 (46)
      ACE, Angiotensin-converting enzyme; ARBs, angiotensin II receptor blockers; BMI, body mass index; IC, intermittent claudication; PAD, peripheral artery disease; SFA, superficial femoral artery.
      Categorical variables are presented as number (%). Continuous variables are presented as mean ± standard deviation.
      PAD features are shown in Table II. No significant differences were found in step length, ABI, and So2; however, IC distance (P = .034), maximum walking distance (P = .006), and all QOL questionnaire scores (P < .001) showed significant improvement after the SEP. Hip ROM (P = .035) and maximum hip torque (right, P = .031; left, P = .044) significantly decreased bilaterally. The maximum tension of the gluteus maximus muscle (right, P = .044; left, P = .042) and the maximum hip joint work (right, P = .048; left, P = .043) significantly decreased bilaterally (Table II).
      Table IIParameters of peripheral artery disease (PAD) and muscle maximum tension and joint work
      Before SEPAfter SEPP value
      Parameters of PAD
       ABI
      Right0.79 ± 0.190.77 ± 0.20.189
      Left0.77 ± 0.210.76 ± 0.19.621
      Parameter of NIRS
       Recovery time, seconds200.1 ± 151.6143.1 ± 104.8.144
       Right ΔSo2, %16.1 ± 12.614.0 ± 12.7.847
       Left ΔSo2, %17.7 ± 12.817.8 ± 13.3.947
      QOL score
       VascuQOL4.2 ± 0.95.7 ± 0.6<.001
       WIQ distance score68.7 ± 19.689.7 ± 14.6<.001
       WIQ speed score29.2 ± 13.361.2 ± 20.0<.001
       WIQ climbing score35.9 ± 18.476.0 ± 23.9<.001
      Right leg step length, m0.50 ± 0.080.50 ± 0.08.664
      Left leg step lengths, m0.51 ± 0.090.50 ± 0.08.872
      Length of IC with the treadmill, m160 ± 128228 ± 187.034
      Maximum walking distance, m453 ± 345702 ± 416.006
      Joint angles, degrees
       Right
      Hip max−13.6 ± 8.2−13.2 ± 9.4.826
      Hip ROM39.4 ± 5.637.6 ± 5.3.035
      Knee max60.7 ± 6.460.8 ± 6.7.951
      Knee ROM57.8 ± 6.756.6 ± 5.3.327
      Ankle max13.7 ± 5.313.2 ± 5.5.757
      Ankle ROM21.8 ± 5.122.4 ± 6.4.671
       Left
      Hip max−13.7 ± 8.2−13.3 ± 9.3.757
      Hip ROM39.2 ± 5.537.7 ± 5.1.037
      Knee max60.7 ± 6.461.2 ± 6.2.792
      Knee ROM57.9 ± 7.057.1 ± 4.9.505
      Ankle max13.7 ± 5.312.7 ± 6.4.608
      Ankle ROM21.7 ± 5.021.5± 8.2.866
      Maximum joint torque, N
       Right
      Hip88.0 ± 18.883.5 ± 19.7.031
      Knee62.5 ± 17.756.8 ± 17.7.251
      Ankle133.4 ± 20.1131.5 ± 26.1.759
       Left
      Hip88.1 ± 18.583.5 ± 20.2.044
      Knee62.3 ± 17.256.3 ± 17.6.213
      Ankle132.6 ± 18.7131.1 ± 25.6.813
      Muscle maximum tension and joint work
       Muscles maximum tension, N
       Right
      Multifidus muscle312.2 ± 116.9329.0 ± 137.6.611
      Gluteus maximus167.6 ± 31.6149.8 ± 44.2.044
      Rectus femoris980.1 ± 151.7961.8 ± 221.5.541
      Vastus intermedius544.0 ± 296.2743.3 ± 447.0.091
      Semimembranosus969.5 ± 114.4931.9 ± 128.2.225
      Gastrocnemius639.0 ± 9.3638.4 ± 13.0.798
      Soleus2000.3 ± 131.12027.4 ± 119.2.547
      Anterior tibial800.9 ± 23.6800.2 ± 50.0.957
       Left
      Multifidus muscle313.6 ± 116.0327.4 ± 139.4.683
      Gluteus maximus167.5 ± 31.5149.3 ± 44.6.042
      Rectus femoris980.0 ± 149.4962.8 ± 219.6.561
      Vastus intermedius551.9 ± 301.5734.8 ± 453.7.122
      Semimembranosus966.6 ± 118.3935.2 ± 128.5.314
      Gastrocnemius638.9 ± 9.2638.8 ± 12.8.974
      Soleus2028.1 ± 107.22027.6 ± 120.2.989
      Anterior tibial801.0 ± 23.6799.7 ± 50.0.917
      Joint work, Nm
       Right
      Hip87.2 ± 20.081.6 ± 20.4.048
      Knee62.5 ± 17.756.8 ± 17.7.193
      Ankle133.4 ± 20.1131.5 ± 26.1.410
       Left
      Hip87.3 ± 19.781.6 ± 20.9.043
      Knee62.3 ± 17.256.3 ± 17.6.111
      Ankle132.6 ± 18.7131.1 ± 25.6.319
      ABI, Ankle-brachial index; IC, intermittent claudication; NIRS, near-infrared spectroscopy; ROM, range of motion; So2, oxygen saturation; SEP, supervised exercise program; VascuQoL, Vascular Quality of Life questionnaire; WIQ, Walking Impairment Questionnaire.
      Values are reported as mean ± standard deviation.
      Cross-sectional CT images showed a significant increase in abdominal (abdominal rectus, P < .001; abdominal oblique, P = .023), trunk (psoas major, P = .005; erector spinae, P = .004), gluteus (right, P = .006; left, P = .016), and thigh (rectus femoris: right, P = .026; left, P = .012) muscles. However, this was not observed in the lower leg muscles (Table III).
      Table IIIOutlining computed tomography (CT) images of skeletal muscle area before and after intervention
      MuscleBefore SEP, cm2After SEP, cm2Change, %P value
      Abdominal rectus8.4 ± 2.89.3 ± 3.219.2<.001
      Abdominal oblique35.2 ± 12.837.4 ± 12.47.1.023
      Psoas major20.1 ± 4.721.4 ± 4.97.1.005
      Erector spinae33.7 ± 9.035.3 ± 9.64.5.004
      Right gluteus34.1 ± 7.036.7 ± 8.37.1.006
      Left gluteus32.7 ± 8.136.1 ± 9.110.4.016
      Right rectus femoris7.7 ± 2.38.3 ± 2.110.7.026
      Left rectus femoris7.2 ± 1.78.0 ± 1.911.9.012
      Right lower leg45.7 ± 10.445.6 ± 10.90.3.961
      Left lower leg43.9 ± 8.844.8 ± 8.82.1.389
      SEP, Supervised exercise program.
      Values are reported as mean ± standard deviation.
      Changes in kinematics after the SEP can be seen in further detail in Videos 1 and 2 (online only).

      Discussion

      After a 3-month structured exercise program using a bicycle ergometer, this study reported improvement in walking distance and questionnaire scores for patients with PAD and IC; however, no improvement was found in the other parameters (step length, ABI, and hemoglobin oxygen saturation). In addition, the effect of SEP was proven by analysis of the motion capture system (decrease in the hip ROM, hip joint torque, hip joint work, and maximum muscle tension of the gluteus maximus) and CT imaging (increase in the cross-sectional area of the abdomen, trunk, and thigh muscles, although not in the lower leg muscles).
      Impaired walking ability in IC patients may be a consequence of reduced leg muscle strength and endurance. The mechanisms that explain impaired muscle strength in PAD patients have not been fully elucidated. Therefore, it was initially assumed that exercise training would affect the muscle tension and relevant joint movements, resulting in improved walking ability. Although the muscle mass of the lumbar major muscle and thigh muscles increased with exercise training, there was less movement at the hip area after the SEP, indicating that the walking technique (including postural stability and walking economy) could be contributing more to the gait improvement than physiologic changes.
      There is one possible mechanism that may be considered to explain the effects of the SEP intervention in gait parameters. The muscles evaluated in this study (rectus abdominis, iliopsoas, erector spinae, rectus femoris, gluteus maximus) perform antigravity activity,
      • Ivanenko Y.
      • Gurfinkel V.S.
      Human postural control.
      and the increase in their cross-sectional area should increase the stability of the standing posture. In exercise physiology, “efficient walking” is defined as walking with less movement of the center of gravity.
      • Cavagna G.A.
      • Thys H.
      • Zamboni A.
      The sources of external work in level walking and running.
      The center of gravity in humans is located in front of the sacrum and moves periodically in the left, right, and vertical direction during walking.
      • Cavagna G.A.
      • Thys H.
      • Zamboni A.
      The sources of external work in level walking and running.
      • Kuo A.D.
      The six determinants of gait and the inverted pendulum analogy: a dynamic walking perspective.
      Walking with less periodic change involves less change in the center of gravity.
      • Cavagna G.A.
      • Thys H.
      • Zamboni A.
      The sources of external work in level walking and running.
      • Kuo A.D.
      The six determinants of gait and the inverted pendulum analogy: a dynamic walking perspective.
      A postural stabilization effect of the SEP would lead to lower energy expenditure compared with the pre-SEP state. Walking with less energy decreases the hip joint movement range, hip joint torque, and maximum muscle tension of the gluteus maximus muscle, which leads to an improvement in walking ability. In this study, changes in the center of gravity before and after exercise training could not be verified; therefore, gait efficiency was not completely proven. Cavagna et al
      • Cavagna G.A.
      • Thys H.
      • Zamboni A.
      The sources of external work in level walking and running.
      advocated analyzing the change in kinetic energy as a function of the position energy and kinetic energy of the center of gravity. Proving energy efficiency by focusing on the change in kinetic energy with normal controls is warranted in the future.
      This study did report the kinematic and muscle changes; however, this could be due to some physiologic changes (ie, improvement in the flow-mediated dilation of the patients' arterial vasculature and consequent improved walking tolerance) caused by the SEP, leading to better kinematics and thus improved muscle volume. These findings might constitute independent changes or combined biologic responses to SEP. However, there is no way to explain the exact mechanism for this improvement.
      Previous studies on motion analysis for PAD patients reported symptomatic improvement; however, they did not reveal a clear mechanism. Crowther et al
      • Crowther R.G.
      • Spinks W.L.
      • Leicht A.S.
      • Sangla K.
      • Quigley F.
      • Golledge J.
      The influence of a long term exercise program on lower limb movement variability and walking performance in patients with peripheral arterial disease.
      reported no significant effect on lower limb movement variability after an SEP. This might be because a two-dimensional capture technique was used in that study, which has been reported to increase measurement error.
      • Sih B.L.
      • Hubbard M.
      • Williams K.R.
      Correcting out-of-plane errors in two-dimensional imaging using nonimage-related information.
      King et al
      • King S.
      • Vanicek N.
      • Mockford K.A.
      • Coughlin P.A.
      The effect of a 3-month supervised exercise programme on gait parameters of patients with peripheral arterial disease and intermittent claudication.
      also failed to show significant changes in any of the gait parameters after an SEP, including peak hip extension, peak ankle plantar flexion, and peak vertical ground reaction force, which might be due to the lack of detailed muscle and biomechanical adaptations. The results of this study were obtained by both the three-dimensional motion capture system and detailed musculoskeletal analysis.
      In the evaluation and measurement of the muscle cross-sectional area on CT images, the modified method of previous reports was adopted for this study. The third lumbar vertebra is often used as a positional reference for tracing the muscle contour on the CT transverse image, with high reliability.
      • Harimoto N.
      • Shirabe K.
      • Yamashita Y.I.
      • Ikegami T.
      • Yoshizumi T.
      • Soejima Y.
      • et al.
      Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma.
      • Matsubara Y.
      • Matsumoto T.
      • Aoyagi Y.
      • Tanaka S.
      • Okadome J.
      • Morisaki K.
      • et al.
      Sarcopenia is a prognostic factor for overall survival in patients with critical limb ischemia.
      In addition to this standard index, the lower end of the ischial bone and the middle part of the fibula were evaluated as measurement standards in this study because the gluteus maximus, rectus femoris, and lower leg muscles were to be evaluated, which cannot be assessed by image evaluation at the position of the third lumbar vertebra.
      The point of this study is that SEP was performed by using a bicycle ergometer. The efficacy of bicycle exercise training is not well understood. On the contrary, the effects of walking have been widely reported.
      • McDermott M.M.
      • Ades P.
      • Guralnik J.M.
      • Dyer A.
      • Ferrucci L.
      • Liu K.
      • et al.
      Treadmill exercise and resistance training in patients with peripheral arterial disease with and without intermittent claudication: a randomized controlled trial.
      • McGuigan M.R.
      • Bronks R.
      • Newton R.U.
      • Sharman M.J.
      • Graham J.C.
      • Cody D.V.
      • et al.
      Resistance training in patients with peripheral arterial disease: effects on myosin isoforms, fiber type distribution, and capillary supply to skeletal muscle.
      • Parmenter B.J.
      • Raymond J.
      • Singh M.A.
      The effect of exercise on fitness and performance-based tests of function in intermittent claudication: a systematic review.
      • Ritti-Dias R.M.
      • Wolosker N.
      • de Moraes Forjaz C.L.
      • Carvalho C.R.
      • Cucato G.G.
      • Leao P.P.
      • et al.
      Strength training increases walking tolerance in intermittent claudication patients: randomized trial.
      In one of these studies, Parmenter et al
      • Parmenter B.J.
      • Raymond J.
      • Singh M.A.
      The effect of exercise on fitness and performance-based tests of function in intermittent claudication: a systematic review.
      reported that the strength of the lumbar and femoral muscles increased 1.42 times after training. In contrast, exercise training using a bicycle ergometer mainly affects the rectus femoris and biceps femoris.
      • Kim S.C.
      • Lee S.Y.
      • Lee Y.I.
      Leg muscle activation and distance setting of the leg cycle ergometer for use by the elderly.
      This study showed an increase in the cross-sectional area of the lumbar and femoral muscles, but no changes were found in the cross-sectional area of the lower leg muscles. The lower leg muscles are more exposed to ischemia; therefore, they have a reduced oxygen supply, decreasing protein synthesis ability. Accordingly, the strengthening effect might be smaller in the lower leg than in the thigh. These findings show that bicycle training might be as useful as walking. In addition, a new method of exercise training, concentrating only on hip pumping to help hip joint movement, might contribute to improving walking ability without performing walking exercise training. Further studies need to assess this speculation in the future.
      Changes in ABI, NIRS, and other important parameters were not observed in this study. However, exercise training has not been found to improve ABI in claudication patients.
      • Murphy T.P.
      • Cutlip D.E.
      • Regensteiner J.G.
      • Mohler E.M.
      • Cohen D.J.
      • Reynolds M.R.
      • et al.
      Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral artery disease.
      To reveal the mechanism, analysis with other modalities, such as angiography and plethysmography, is warranted in the future.
      This study has some limitations. First, a certain degree of error should be inevitable in this three-dimensional motion analysis. In the current system, patients' height and weight were used to optimize the model correspondence to patients' physique. However, the number of joints reproduced in the musculoskeletal model was 155.
      • Nakamura Y.
      • Hanafusa H.
      Inverse kinematic solutions with singularity robustness for robot manipulator control.
      To increase model precision, more parameters should be included, and improved calculations are necessary.
      A second limitation is the adequacy of the inverse kinematics analysis and inverse dynamics analysis. According to the calculation of inverse dynamics in previous reports, the evaluation function of inverse kinematics analysis is the mainstream nonlinear optimization method to obtain the coordinates that minimize the error from the target position.
      • Nakamura Y.
      • Hanafusa H.
      Inverse kinematic solutions with singularity robustness for robot manipulator control.
      • Zhao J.
      • Badler N.I.
      Inverse kinematics positioning using nonlinear programming for highly articulated figures.
      However, few previous studies have determined muscle tension from torque by inverse dynamics analysis. The evaluation function of inverse dynamics analysis is a theoretically derived solution method; however, further verification is warranted because it is not yet an established method.
      Third, the maximum voluntary strength could not be measured, which is considered to accurately reflect the strength of each muscle. For the measurement of the maximum voluntary strength, an isokinetic or isometric dynamometer would be required.

      Conclusions

      Bicycle exercise training improved the QOL and walking distance and decreased hip movement. The results of this study suggest that bicycle training might be as useful as walking exercise training in PAD patients.

      Author contributions

      Conception and design: MH, KH, HK, TM, YI, AM, YN
      Analysis and interpretation: MH, KH
      Data collection: YI, AM
      Writing the article: MH, KH, YI
      Critical revision of the article: KH, HK, TM, YI, AM, YN
      Final approval of the article: MH, KH, HK, TM, YI, AM, YN
      Statistical analysis: MH
      Obtained funding: Not applicable
      Overall responsibility: KH

      Appendix (online only).

      References

        • Gardner A.W.
        • Poehlman E.T.
        Exercise rehabilitation programs for the treatment of claudication pain. A meta-analysis.
        JAMA. 1995; 274: 975-980
        • Robeer G.G.
        • Brandsma J.W.
        • van den Heuvel S.P.
        • Smit B.
        • Oostendorp R.A.
        • Wittens C.H.
        Exercise therapy for intermittent claudication: a review of the quality of randomised clinical trials and evaluation of predictive factors.
        Eur J Vasc Endovasc Surg. 1998; 15: 36-43
        • Gardner A.W.
        • Montgomery P.S.
        • Flinn W.R.
        • Katzel L.I.
        The effect of exercise intensity on the response to exercise rehabilitation in patients with intermittent claudication.
        J Vasc Surg. 2005; 42: 702-709
        • Nicholson C.D.
        • Angersbach D.
        • Wilke R.
        The effect of physical training on rat calf muscle, oxygen tension, blood flow, metabolism and function in an animal model of chronic occlusive peripheral vascular disease.
        Int J Sports Med. 1992; 13: 60-64
        • Weiss T.
        • Fujita Y.
        • Kreimeier U.
        • Messmer K.
        Effect of intensive walking exercise on skeletal muscle blood flow in intermittent claudication.
        Angiology. 1992; 43: 63-71
        • Yang H.T.
        • Dinn R.F.
        • Terjung R.L.
        Training increases muscle blood flow in rats with peripheral arterial insufficiency.
        J Appl Physiol (1985). 1990; 69: 1353-1359
        • Lloyd P.G.
        • Yang H.T.
        • Terjung R.L.
        Arteriogenesis and angiogenesis in rat ischemic hindlimb: role of nitric oxide.
        Am J Physiol Heart Circ Physiol. 2001; 281: H2528-H2538
        • Niebauer J.
        • Cooke J.P.
        Cardiovascular effects of exercise: role of endothelial shear stress.
        J Am Coll Cardiol. 1996; 28: 1652-1660
        • Terjung R.L.
        • Mathien G.M.
        • Erney T.P.
        • Ogilvie R.W.
        Peripheral adaptations to low blood flow in muscle during exercise.
        Am J Cardiol. 1988; 62: 15E-19E
        • Hiatt W.R.
        • Regensteiner J.G.
        • Hargarten M.E.
        • Wolfel E.E.
        • Brass E.P.
        Benefit of exercise conditioning for patients with peripheral arterial disease.
        Circulation. 1990; 81: 602-609
        • Hiatt W.R.
        • Regensteiner J.G.
        • Wolfel E.E.
        • Carry M.R.
        • Brass E.P.
        Effect of exercise training on skeletal muscle histology and metabolism in peripheral arterial disease.
        J Appl Physiol (1985). 1996; 81: 780-788
        • Capecchi P.L.
        • Pasini F.L.
        • Cati G.
        • Colafati M.
        • Acciavatti A.
        • Ceccatelli L.
        • et al.
        Experimental model of short-time exercise-induced preconditioning in POAD patients.
        Angiology. 1997; 48: 469-480
        • Ernst E.E.
        • Matrai A.
        Intermittent claudication, exercise, and blood rheology.
        Circulation. 1987; 76: 1110-1114
        • Hiatt W.R.
        • Wolfel E.E.
        • Meier R.H.
        • Regensteiner J.G.
        Superiority of treadmill walking exercise versus strength training for patients with peripheral arterial disease. Implications for the mechanism of the training response.
        Circulation. 1994; 90: 1866-1874
        • Womack C.J.
        • Sieminski D.J.
        • Katzel L.I.
        • Yataco A.
        • Gardner A.W.
        Improved walking economy in patients with peripheral arterial occlusive disease.
        Med Sci Sports Exerc. 1997; 29: 1286-1290
        • Edwards A.T.
        • Blann A.D.
        • Suarez-Mendez V.J.
        • Lardi A.M.
        • McCollum C.N.
        Systemic responses in patients with intermittent claudication after treadmill exercise.
        Br J Surg. 1994; 81: 1738-1741
        • Khaira H.S.
        • Maxwell S.R.
        • Shearman C.P.
        Antioxidant consumption during exercise in intermittent claudication.
        Br J Surg. 1995; 82: 1660-1662
        • Tisi P.V.
        • Hulse M.
        • Chulakadabba A.
        • Gosling P.
        • Shearman C.P.
        Exercise training for intermittent claudication: does it adversely affect biochemical markers of the exercise-induced inflammatory response?.
        Eur J Vasc Endovasc Surg. 1997; 14: 344-350
        • Green D.J.
        • Hopman M.T.
        • Padilla J.
        • Laughlin M.H.
        • Thijssen D.H.
        Vascular adaptation to exercise in humans: role of hemodynamic stimuli.
        Physiol Rev. 2017; 97: 495-528
        • Nakamura Y.
        • Yamane K.
        • Fujita Y.
        • Suzuki I.
        Somatosensory computation for man-machine interface LE from motion-capture data and musculoskeletal human model.
        IEEE Trans Robot. 2005; 21: 58-66
        • Komiyama T.
        • Shigematsu H.
        • Yasuhara H.
        • Muto T.
        Near-infrared spectroscopy grades the severity of intermittent claudication in diabetics more accurately than ankle pressure measurement.
        Br J Surg. 2000; 87: 459-466
        • Vardi M.
        • Nini A.
        Near-infrared spectroscopy for evaluation of peripheral vascular disease. A systematic review of literature.
        Eur J Vasc Endovasc Surg. 2008; 35: 68-74
        • Gardner A.W.
        • Parker D.E.
        • Webb N.
        • Montgomery P.S.
        • Scott K.J.
        • Blevins S.M.
        Calf muscle hemoglobin oxygen saturation characteristics and exercise performance in patients with intermittent claudication.
        J Vasc Surg. 2008; 48: 644-649
        • Harimoto N.
        • Shirabe K.
        • Yamashita Y.I.
        • Ikegami T.
        • Yoshizumi T.
        • Soejima Y.
        • et al.
        Sarcopenia as a predictor of prognosis in patients following hepatectomy for hepatocellular carcinoma.
        Br J Surg. 2013; 100: 1523-1530
        • Matsubara Y.
        • Matsumoto T.
        • Aoyagi Y.
        • Tanaka S.
        • Okadome J.
        • Morisaki K.
        • et al.
        Sarcopenia is a prognostic factor for overall survival in patients with critical limb ischemia.
        J Vasc Surg. 2015; 61: 945-950
        • Nicolai S.P.
        • Kruidenier L.M.
        • Rouwet E.V.
        • Graffius K.
        • Prins M.H.
        • Teijink J.A.
        The walking impairment questionnaire: an effective tool to assess the effect of treatment in patients with intermittent claudication.
        J Vasc Surg. 2009; 50: 89-94
        • Mehta T.
        • Venkata Subramaniam A.
        • Chetter I.
        • McCollum P.
        Assessing the validity and responsiveness of disease-specific quality of life instruments in intermittent claudication.
        Eur J Vasc Endovasc Surg. 2006; 31: 46-52
        • Morgan M.B.
        • Crayford T.
        • Murrin B.
        • Fraser S.C.
        Developing the Vascular Quality of Life Questionnaire: a new disease-specific quality of life measure for use in lower limb ischemia.
        J Vasc Surg. 2001; 33: 679-687
        • Ivanenko Y.
        • Gurfinkel V.S.
        Human postural control.
        Front Neurosci. 2018; 12: 171
        • Cavagna G.A.
        • Thys H.
        • Zamboni A.
        The sources of external work in level walking and running.
        J Physiol. 1976; 262: 639-657
        • Kuo A.D.
        The six determinants of gait and the inverted pendulum analogy: a dynamic walking perspective.
        Hum Mov Sci. 2007; 26: 617-656
        • Crowther R.G.
        • Spinks W.L.
        • Leicht A.S.
        • Sangla K.
        • Quigley F.
        • Golledge J.
        The influence of a long term exercise program on lower limb movement variability and walking performance in patients with peripheral arterial disease.
        Hum Mov Sci. 2009; 28: 494-503
        • Sih B.L.
        • Hubbard M.
        • Williams K.R.
        Correcting out-of-plane errors in two-dimensional imaging using nonimage-related information.
        J Biomech. 2001; 34: 257-260
        • King S.
        • Vanicek N.
        • Mockford K.A.
        • Coughlin P.A.
        The effect of a 3-month supervised exercise programme on gait parameters of patients with peripheral arterial disease and intermittent claudication.
        Clin Biomech (Bristol, Avon). 2012; 27: 845-851
        • McDermott M.M.
        • Ades P.
        • Guralnik J.M.
        • Dyer A.
        • Ferrucci L.
        • Liu K.
        • et al.
        Treadmill exercise and resistance training in patients with peripheral arterial disease with and without intermittent claudication: a randomized controlled trial.
        JAMA. 2009; 301: 165-174
        • McGuigan M.R.
        • Bronks R.
        • Newton R.U.
        • Sharman M.J.
        • Graham J.C.
        • Cody D.V.
        • et al.
        Resistance training in patients with peripheral arterial disease: effects on myosin isoforms, fiber type distribution, and capillary supply to skeletal muscle.
        J Gerontol A Biol Sci Med Sci. 2001; 56: B302-B310
        • Parmenter B.J.
        • Raymond J.
        • Singh M.A.
        The effect of exercise on fitness and performance-based tests of function in intermittent claudication: a systematic review.
        Sports Med. 2013; 43: 513-524
        • Ritti-Dias R.M.
        • Wolosker N.
        • de Moraes Forjaz C.L.
        • Carvalho C.R.
        • Cucato G.G.
        • Leao P.P.
        • et al.
        Strength training increases walking tolerance in intermittent claudication patients: randomized trial.
        J Vasc Surg. 2010; 51: 89-95
        • Kim S.C.
        • Lee S.Y.
        • Lee Y.I.
        Leg muscle activation and distance setting of the leg cycle ergometer for use by the elderly.
        J Phys Ther Sci. 2014; 26: 1593-1595
        • Murphy T.P.
        • Cutlip D.E.
        • Regensteiner J.G.
        • Mohler E.M.
        • Cohen D.J.
        • Reynolds M.R.
        • et al.
        Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral artery disease.
        Circulation. 2011; 125: 130-139
        • Nakamura Y.
        • Hanafusa H.
        Inverse kinematic solutions with singularity robustness for robot manipulator control.
        J Dyn Sys Meas Control. 1986; 108: 163-171
        • Zhao J.
        • Badler N.I.
        Inverse kinematics positioning using nonlinear programming for highly articulated figures.
        ACM Trans Graph. 1994; 13: 313-336