Blood flow restriction in the presence or absence of muscle contractions does not preserve vasculature structure and function following 14–days of limb immobilization

Cohen, Jeremy N.; Slysz, Joshua T.; King, Trevor J.; Coates, Alexandra M.; King, Robert T.; Burr, Jamie F.

doi:10.1007/s00421-021-04715-3

Blood flow restriction in the presence or absence of muscle contractions does not preserve vasculature structure and function following 14–days of limb immobilization

Original Article
Published: 18 May 2021

Volume 121, pages 2437–2447, (2021)
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European Journal of Applied Physiology Aims and scope Submit manuscript

Jeremy N. Cohen¹,
Joshua T. Slysz^1,2,
Trevor J. King^1,3,
Alexandra M. Coates¹,
Robert T. King¹ &
…
Jamie F. Burr ORCID: orcid.org/0000-0002-5449-3352¹

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Abstract

Purpose

Limb immobilization causes local vasculature to experience detrimental adaptations. Simple strategies to increase blood flow (heating, fidgeting) successfully prevent acute (≤ 1 day) impairments; however, none have leveraged the hyperemic response over prolonged periods (weeks) mirroring injury rehabilitation. Throughout a 14-day unilateral limb immobilization, we sought to preserve vascular structure and responsiveness by repeatedly activating a reactive hyperemic response via blood flow restriction (BFR) and amplifying this stimulus by combining BFR with electric muscle stimulation (EMS).

Methods

Young healthy adults (M:F = 14:17, age = 22.4 ± 3.7 years) were randomly assigned to control, BFR, or BFR + EMS groups. BFR and BFR + EMS groups were treated for 30 min twice daily (3 × 10 min ischemia–reperfusion cycles; 15% maximal voluntary contraction EMS), 5 days/week (20 total sessions). Before and after immobilization, artery diameter, flow-mediated dilation (FMD) and blood flow measures were collected in the superficial femoral artery (SFA).

Results

Following immobilization, there was less retrograde blood velocity (+ 1.8 ± 3.6 cm s⁻¹, P = 0.01), but not retrograde shear (P = 0.097). All groups displayed reduced baseline and peak SFA diameter following immobilization (− 0.46 ± 0.41 mm and − 0.43 ± 0.39 mm, P < 0.01); however, there were no differences by group or across time for FMD (% diameter change, shear-corrected, or allometrically scaled) nor microvascular function assessed by peak flow capacity.

Conclusion

Following immobilization, our results reveal (1) neither BFR nor BFR + EMS mitigate artery structure impairments, (2) intervention-induced shear stress did not affect vascular function assessed by FMD, and (3) retrograde blood velocity is reduced at rest offering potential insight to mechanisms of flow regulation. In conclusion, BFR appears insufficient as a treatment strategy for preventing macrovascular dysfunction during limb immobilization.

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Data availability

Relevant study data are available from the corresponding author upon reasonable request.

Abbreviations

BFR:: Blood flow restriction
EMS:: Electric muscle stimulation
FMD:: Flow-mediated dilation
MAP:: Mean arterial pressure
MBV:: Mean blood velocity
NO:: Nitric oxide
OSI:: Oscillatory shear index
PWV:: Pulse wave velocity
SFA:: Superficial femoral artery
SR:: Shear rate
SR_60AUC :: Shear rate area-under-curve first 60 s

References

Atkinson G, Batterham AM (2013) Allometric scaling of diameter change in the original flow-mediated dilation protocol. Atherosclerosis 226:425–427. https://doi.org/10.1016/j.atherosclerosis.2012.11.027
Article CAS PubMed Google Scholar
Betik AC, Luckham VB, Hughson RL (2004) Flow-mediated dilation in human brachial artery after different circulatory occlusion conditions. Am J Physiol Hear Circ Physiol 286:442–448. https://doi.org/10.1152/ajpheart.00314.2003.-Different
Article Google Scholar
Bleeker MWP, De Groot PCE, Poelkens F et al (2005a) Vascular adaptation to 4 wk of deconditioning by unilateral lower limb suspension. Am J Physiol Hear Circ Physiol 288:H1747–H1755. https://doi.org/10.1152/ajpheart
Article CAS Google Scholar
Bleeker MWP, De Groot PCE, Rongen GA et al (2005b) Vascular adaptation to deconditioning and the effect of an exercise countermeasure: results of the Berlin Bed Rest study. J Appl Physiol 99:1293–1300. https://doi.org/10.1152/japplphysiol.00118.2005
Article PubMed Google Scholar
Bonnin P, Ben DA, Benessiano J et al (2001) Enhanced flow-dependent vasodilatation after bed rest, a possible mechanism for orthostatic intolerance in humans. Eur J Appl Physiol 85:420–426. https://doi.org/10.1007/s004210100483
Article CAS PubMed Google Scholar
Brown MD, Cotter MA, Hudlická O, Vrbová G (1976) The effects of different patterns of muscle activity on capillary density, mechanical properties and structure of slow and fast rabbit muscles. Pflügers Arch Eur J Physiol 361:241–250. https://doi.org/10.1007/BF00587288
Article CAS Google Scholar
Christiansen D, Eibye K, Hostrup M, Bangsbo J (2020) Training with blood flow restriction increases femoral artery diameter and thigh oxygen delivery during knee-extensor exercise in recreationally trained men. J Physiol 598:2337–2353. https://doi.org/10.1113/JP279554
Article CAS PubMed Google Scholar
Cohen J, Pignanelli C, Burr J (2020) The effect of body position on measures of arterial stiffness in humans. J Vasc Res 57:143–151. https://doi.org/10.1159/000506351
Article PubMed Google Scholar
Dhindsa M, Sommerlad SM, DeVan AE et al (2008) Interrelationships among noninvasive measures of postischemic macro- and microvascular reactivity. J Appl Physiol 105:427–432. https://doi.org/10.1152/japplphysiol.90431.2008
Article PubMed PubMed Central Google Scholar
Dinenno FA, Tanaka H, Monahan KD et al (2001) Regular endurance exercise induces expansive arterial remodelling in the trained limbs of healthy men. J Physiol 534:287–295. https://doi.org/10.1111/j.1469-7793.2001.00287.x
Article CAS PubMed PubMed Central Google Scholar
Egginton S, Hudlická O (1999) Early changes in performance, blood flow and capillary fine structure in rat fast muscles induced by electrical stimulation. J Physiol 515:265–275. https://doi.org/10.1111/j.1469-7793.1999.265ad.x
Article CAS PubMed PubMed Central Google Scholar
Gifford JR, Hanson BE, Proffit M et al (2020) Indices of leg resistance artery function are independently related to cycling V̇O2 max. Physiol Rep. 8:e14551. https://doi.org/10.14814/phy2.14551
Article PubMed PubMed Central Google Scholar
Groot HJ, Rossman MJ, Garten RS et al (2016) The effect of physical activity on passive leg movement-induced vasodilation with age. Med Sci Sports Exerc 48:1548–1557. https://doi.org/10.1249/MSS.0000000000000936
Article PubMed PubMed Central Google Scholar
Hamburg NM, McMackin CJ, Huang AL et al (2007) Physical inactivity rapidly induces insulin resistance and microvascular dysfunction in healthy volunteers. Arterioscler Thromb Vasc Biol 27:2650–2656. https://doi.org/10.1161/ATVBAHA.107.153288
Article CAS PubMed PubMed Central Google Scholar
Harris RA, Padilla J, Rink LD, Wallace JP (2006) Variability of flow-mediated dilation measurements with repetitive reactive hyperemia. Vasc Med 11:1–6. https://doi.org/10.1191/1358863x06vm641oa
Article PubMed Google Scholar
Hodges GJ, Stewart DG, Davison PJ, Cheung SS (2018) Episodic bouts of hyperaemia and shear stress improve arterial blood flow and endothelial function. Eur J Appl Physiol 118:795–803. https://doi.org/10.1007/s00421-018-3805-3
Article PubMed Google Scholar
Horiuchi M, Endo J, Thijssen DHJ (2015) Impact of ischemic preconditioning on functional sympatholysis during handgrip exercise in humans. Physiol Rep 3:1–9. https://doi.org/10.14814/phy2.12304
Article Google Scholar
Hudlicka O, Brown MD (2009) Adaptation of skeletal muscle microvasculature to increased or decreased blood flow: role of shear stress, nitric oxide and vascular endothelial growth factor. J Vasc Res 46:504–512. https://doi.org/10.1159/000226127
Article CAS PubMed Google Scholar
Hunt JEA, Walton LA, Ferguson RA (2012) Brachial artery modifications to blood flow-restricted handgrip training and detraining. J Appl Physiol 112:956–961. https://doi.org/10.1152/japplphysiol.00905.2011
Article PubMed Google Scholar
Joannides R, Haefeli WE, Linder L et al (1995) Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 91:1314–1319. https://doi.org/10.1161/01.CIR.91.5.1314
Article CAS PubMed Google Scholar
Johnson BD, Mather KJ, Newcomer SC et al (2012) Brachial artery flow-mediated dilation following exercise with augmented oscillatory and retrograde shear rate. Cardiovasc Ultrasound 10:1. https://doi.org/10.1186/1476-7120-10-34
Article Google Scholar
Jones H, Nyakayiru J, Bailey TG et al (2015) Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males. Eur J Prev Cardiol 22:1083–1087. https://doi.org/10.1177/2047487314547657
Article PubMed Google Scholar
Kim EJ, Park CG, Park JS et al (2007) Relationship between blood pressure parameters and pulse wave velocity in normotensive and hypertensive subjects: Invasive study. J Hum Hypertens 21:141–148. https://doi.org/10.1038/sj.jhh.1002120
Article CAS PubMed Google Scholar
King TJ, Schmitter SM, Pyke KE (2017) Assessment of flow-mediated dilatation in the superficial femoral artery using a sustained shear stress stimulus via calf plantar-flexion exercise. Exp Physiol 102:725–737. https://doi.org/10.1113/EP085980
Article CAS PubMed Google Scholar
Mettler JA, Magee DM, Doucet BM (2018) High-frequency neuromuscular electrical stimulation increases anabolic signaling. Med Sci Sports Exerc 50:1540–1548. https://doi.org/10.1249/MSS.0000000000001610
Article CAS PubMed Google Scholar
Morishima T, Restaino RM, Walsh LK et al (2016) Prolonged sitting-induced leg endothelial dysfunction is prevented by fidgeting. Am J Physiol - Hear Circ Physiol 311:H177–H182. https://doi.org/10.1152/ajpheart.00297.2016
Article Google Scholar
Mortensen SP, Mørkeberg J, Thaning P et al (2012) Two weeks of muscle immobilization impairs functional sympatholysis but increases exercise hyperemia and the vasodilatory responsiveness to infused ATP. Am J Physiol Hear Circ Physiol 302:2074–2082. https://doi.org/10.1152/ajpheart.01204.2011.-During
Article Google Scholar
Natsume T, Ozaki H, Saito AI et al (2015) Effects of Electrostimulation with Blood Flow Restriction on Muscle Size and Strength. Med Sci Sports Exerc 47:2621–2627. https://doi.org/10.1249/MSS.0000000000000722
Article PubMed Google Scholar
Naylor LH, Weisbrod CJ, O’Driscoll G, Green DJ (2005) Measuring peripheral resistance and conduit arterial structure in humans using Doppler ultrasound. J Appl Physiol 98:2311–2315. https://doi.org/10.1152/japplphysiol.01047.2004
Article PubMed Google Scholar
Naylor LH, Carter H, FitzSimons MG et al (2011) Repeated increases in blood flow, independent of exercise, enhance conduit artery vasodilator function in humans. Am J Physiol Hear Circ Physiol 300:664–669. https://doi.org/10.1152/ajpheart.00985.2010
Article CAS Google Scholar
Nielsen JL, Frandsen U, Jensen KY et al (2020) Skeletal muscle microvascular changes in response to short-term blood flow restricted training—exercise-induced adaptations and signs of perivascular stress. Front Physiol 11:556. https://doi.org/10.3389/fphys.2020.00556
Article PubMed PubMed Central Google Scholar
Padilla J, Simmons GH, Fadel PJ et al (2011) Impact of aging on conduit artery retrograde and oscillatory shear at rest and during exercise: role of nitric oxide. Hypertension 57:484–489. https://doi.org/10.1161/HYPERTENSIONAHA.110.165365
Article CAS PubMed Google Scholar
Patterson SD, Brandner CR (2018) The role of blood flow restriction training for applied practitioners: a questionnaire-based survey. J Sports Sci 36:123–130. https://doi.org/10.1080/02640414.2017.1284341
Article PubMed Google Scholar
Patterson SD, Hughes L, Warmington S et al (2019) Blood flow restriction exercise: considerations of methodology, application, and safety. Front Physiol 10:533. https://doi.org/10.3389/fphys.2019.00533
Article PubMed PubMed Central Google Scholar
Pyke KE, Tschakovsky ME (2005) The relationship between shear stress and flow-mediated dilatation: Implications for the assessment of endothelial function. J Physiol 568:357–369. https://doi.org/10.1113/jphysiol.2005.089755
Article CAS PubMed PubMed Central Google Scholar
Pyke KE, Dwyer EM, Tschakovsky ME (2004) Impact of controlling shear rate on flow-mediated dilation responses in the brachial artery of humans. J Appl Physiol 97:499–508. https://doi.org/10.1152/japplphysiol.01245.2003
Article PubMed Google Scholar
Rådegran G, Saltin B (2000) Human femoral artery diameter in relation to knee extensor muscle mass, peak blood flow, and oxygen uptake. Am J Physiol - Hear Circ Physiol 278:H162–H167. https://doi.org/10.1152/ajpheart.2000.278.1.h162
Article Google Scholar
Rakobowchuk M, Crozier J, Glover EI et al (2011) Short-term unilateral leg immobilization alters peripheral but not central arterial structure and function in healthy young humans. Eur J Appl Physiol 111:203–210. https://doi.org/10.1007/s00421-010-1636-y
Article PubMed Google Scholar
Restaino RM, Holwerda SW, Credeur DP et al (2015) Impact of prolonged sitting on lower and upper limb micro- and macrovascular dilator function. Exp Physiol 100:829–838. https://doi.org/10.1113/EP085238
Article PubMed PubMed Central Google Scholar
Restaino RM, Walsh LK, Morishima T et al (2016) Endothelial dysfunction following prolonged sitting is mediated by a reduction in shear stress. Am J Physiol Hear Circ Physiol 310:H648–H653. https://doi.org/10.1152/ajpheart.00943.2015
Article Google Scholar
Rudic RD, Bucci M, Fulton D et al (2000) Temporal events underlying arterial remodeling after chronic flow reduction in mice: correlation of structural changes with a deficit in basal nitric oxide synthesis. Circ Res 86:1160–1166. https://doi.org/10.1161/01.RES.86.11.1160
Article CAS PubMed Google Scholar
Rytter N, Carter H, Piil P et al (2020a) Ischemic preconditioning improves microvascular endothelial function in remote vasculature by enhanced Prostacyclin production. J Am Heart Assoc 9:e016017. https://doi.org/10.1161/JAHA.120.016017
Article CAS PubMed PubMed Central Google Scholar
Rytter N, Piil P, Carter H et al (2020b) Microvascular function is impaired after short-term immobilization in healthy men. Med Sci Sport Exerc 52:2107–2116. https://doi.org/10.1249/MSS.0000000000002369
Article CAS Google Scholar
Seals DR, Jablonski KL, Donato AJ (2011) Aging and vascular endothelial function in humans. Clin Sci 120:357–375. https://doi.org/10.1042/CS20100476
Article CAS Google Scholar
Shoemaker JK, Hogeman CS, Leuenberger UA et al (1998) Sympathetic discharge and vascular resistance after bed rest. J Appl Physiol 84:612–617. https://doi.org/10.1152/jappl.1998.84.2.612
Article CAS PubMed Google Scholar
Shoemaker JK, Badrov MB, Al-Khazraji BK, Jackson DN (2016) Neural control of vascular function in skeletal muscle. Compr Physiol 6:303–329. https://doi.org/10.1002/cphy.c150004
Article Google Scholar
Slysz JT, Burr JF (2018) The effects of blood flow restricted electrostimulation on strength and hypertrophy. J Sport Rehabil 27:257–262. https://doi.org/10.1123/jsr.2017-0002
Article PubMed Google Scholar
Slysz J, Stultz J, Burr JF (2016) The efficacy of blood flow restricted exercise: a systematic review and meta-analysis. J Sci Med Sport 19:669–675. https://doi.org/10.1016/j.jsams.2015.09.005
Article PubMed Google Scholar
Slysz J, Boston M, King R et al (2021) Blood flow restriction combined with electrical stimulation attenuates thigh muscle disuse atrophy. Med Sci Sport Exerc 53:1033–1040. https://doi.org/10.1249/MSS.0000000000002544
Article Google Scholar
Teixeira AL, Padilla J, Vianna LC (2017) Impaired popliteal artery flow-mediated dilation caused by reduced daily physical activity is prevented by increased shear stress. J Appl Physiol 123:49–54. https://doi.org/10.1152/japplphysiol.00001.2017
Article PubMed PubMed Central Google Scholar
Thijssen DHJ, Maiorana AJ, O’Driscoll G et al (2010) Impact of inactivity and exercise on the vasculature in humans. Eur J Appl Physiol 108:845–875. https://doi.org/10.1007/s00421-009-1260-x
Article PubMed Google Scholar
Thijssen DHJ, Bruno RM, Van Mil ACCM et al (2019) Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J 40:2534–2547. https://doi.org/10.1093/eurheartj/ehz350
Article PubMed Google Scholar
Thosar SS, Bielko SL, Mather KJ et al (2015) Effect of prolonged sitting and breaks in sitting time on endothelial function. Med Sci Sports Exerc 47:843–849. https://doi.org/10.1249/MSS.0000000000000479
Article PubMed Google Scholar
Tsang GMK, Green MA, Crow AJ et al (1994) Chronic muscle stimulation improves ischaemic muscle performance in patients with peripheral vascular disease. Eur J Vasc Surg 8:419–422. https://doi.org/10.1016/S0950-821X(05)80960-0
Article CAS PubMed Google Scholar
Vlachopoulos C, Aznaouridis K, Stefanadis C (2010) Prediction of cardiovascular events and all-cause mortality with arterial stiffness. A systematic review and meta-analysis. J Am Coll Cardiol 55:1318–1327. https://doi.org/10.1016/j.jacc.2009.10.061
Article PubMed Google Scholar
Vranish JR, Young BE, Stephens BY et al (2018) Brief periods of inactivity reduce leg microvascular, but not macrovascular, function in healthy young men. Exp Physiol 103:1425–1434. https://doi.org/10.1113/EP086918
Article PubMed Google Scholar
Wenner MM, Stachenfeld NS (2020) Counterpoint: Investigators should not control for menstrual cycle phase when performing studies of vascular control that include women. J Appl Physiol japplphysiol.00443.2020. https://doi.org/10.1152/japplphysiol.00443.2020
Williams JS, Dunford EC, MacDonald MJ (2020) Impact of the menstrual cycle on peripheral vascular function in premenopausal women: systematic review and meta-analysis. Am J Physiol Circ Physiol 319:H1327–H1337. https://doi.org/10.1152/ajpheart.00341.2020
Article CAS Google Scholar

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Funding

This work was supported by a Natural Science and Engineering Research Council (NSERC) Discovery grant (JFB).

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Authors and Affiliations

Human Health and Nutritional Sciences, University of Guelph, 50 Stone Road East, Guelph, ON, N1G 2W1, Canada
Jeremy N. Cohen, Joshua T. Slysz, Trevor J. King, Alexandra M. Coates, Robert T. King & Jamie F. Burr
Department of Medicine, Northwestern University, Chicago, USA
Joshua T. Slysz
Faculty of Kinesiology, McMaster University, Hamilton, Canada
Trevor J. King

Authors

Jeremy N. Cohen
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Joshua T. Slysz
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Trevor J. King
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Alexandra M. Coates
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Robert T. King
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Contributions

JTS and JFB conceived and designed the study; JTS, TJK, AMC and RTK collected data; JNC analyzed data; JNC, JTS, TJK and JFB interpreted results; JNC drafted the manuscript. All authors read and approved the final version of the manuscript.

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Correspondence to Jamie F. Burr.

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This study was approved by the institutional ethics review committee (REB# 17–12-006).

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Communicated by Ellen Adele Dawson.

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Cohen, J.N., Slysz, J.T., King, T.J. et al. Blood flow restriction in the presence or absence of muscle contractions does not preserve vasculature structure and function following 14–days of limb immobilization. Eur J Appl Physiol 121, 2437–2447 (2021). https://doi.org/10.1007/s00421-021-04715-3

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Received: 26 January 2021
Accepted: 07 May 2021
Published: 18 May 2021
Issue Date: September 2021
DOI: https://doi.org/10.1007/s00421-021-04715-3

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Blood flow restriction in the presence or absence of muscle contractions does not preserve vasculature structure and function following 14–days of limb immobilization