{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:25:17Z","timestamp":1790270717437,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"am","delay-in-days":326,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T00:00:00Z","timestamp":1617840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["19PRE34370079"],"award-info":[{"award-number":["19PRE34370079"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL135135"],"award-info":[{"award-number":["R01HL135135"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL152152"],"award-info":[{"award-number":["R01HL152152"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1351341"],"award-info":[{"award-number":["1351341"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>We present the first <jats:italic>in vivo<\/jats:italic> evidence that lymphatic contraction can entrain with an external oscillatory mechanical stimulus.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Lymphatic injury can alter collecting lymphatic contractility, but not much is known about how its mechanosensitivity to external pressure is affected, which is crucial given the current pressure application methods for treating lymphoedema.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show that oscillatory pressure waves (OPW), akin to intermittent pneumatic compression (IPC) therapy, optimally entrain lymphatic contractility and modulate function depending on the frequency and propagation speed of the OPW.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show that the OPW\u2010induced entrainment and contractile function in the intact collecting lymphatics are enhanced 28\u00a0days after a contralateral lymphatic ligation surgery.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The results show that IPC efficacy can be improved through proper selection of OPW parameters, and that collecting lymphatics adapt their function and mechanosensitivity after a contralateral injury, switching their behaviour to a pump\u2010like configuration that may be more suited to the altered microenvironment.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Intermittent pneumatic compression (IPC) is commonly used to control the swelling due to lymphoedema, possibly modulating the collecting lymphatic function. Lymphoedema causes lymphatic contractile dysfunction, but the consequent alterations in the mechanosensitivity of lymphatics to IPC is not known. In the present work, the spatiotemporally varying oscillatory pressure waves (OPW) generated during IPC were simulated to study the modulation of lymphatic function by OPW under physiological and pathological conditions. OPW with three temporal frequencies and three propagation speeds were applied to rat tail collecting lymphatics. The entrainment of the lymphatics to OPW was significantly higher at a frequency of 0.05\u00a0Hz compared with 0.1\u00a0Hz and 0.2\u00a0Hz (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0054 and <jats:italic>P<\/jats:italic>\u00a0=\u00a00.014, respectively), but did not depend on the OPW propagation speed. Lymphatic function was significantly higher at a frequency of 0.05\u00a0Hz and propagation speed of 2.55\u00a0mm\/s (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.015). Exogenous nitric oxide was not found to alter OPW\u2010induced entrainment. A contralateral lymphatic ligation surgery was performed to simulate partial lymphatic injury in rat tails. The intact vessels showed a significant increase in entrainment to OPW, 28\u00a0days after ligation (compared with sham) (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.016), with a similar increase in lymphatic transport function (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0029). The results suggest an enhanced mechanosensitivity of the lymphatics, along with a transition to a pump\u2010like behaviour, in response to a lymphatic injury. These results enhance our fundamental understanding of how lymphatic mechanosensitivity assists the coordination of lymphatic contractility and how this might be leveraged in IPC therapy.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp281206","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T06:41:36Z","timestamp":1614580896000},"page":"2699-2721","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Lymphatic injury alters the contractility and mechanosensitivity of collecting lymphatics to intermittent pneumatic compression"],"prefix":"10.1113","volume":"599","author":[{"given":"Anish","family":"Mukherjee","sequence":"first","affiliation":[{"name":"School of Electrical and Computer Engineering Georgia Institute of Technology  Atlanta GA 30332 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0713-4485","authenticated-orcid":false,"given":"Zhanna","family":"Nepiyushchikh","sequence":"additional","affiliation":[{"name":"George W. Woodruff School of Mechanical Engineering Georgia Institute of Technology  Atlanta Georgia 30332 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleftheria","family":"Michalaki","sequence":"additional","affiliation":[{"name":"George W. Woodruff School of Mechanical Engineering Georgia Institute of Technology  Atlanta Georgia 30332 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0384-1625","authenticated-orcid":false,"given":"J. Brandon","family":"Dixon","sequence":"additional","affiliation":[{"name":"George W. Woodruff School of Mechanical Engineering Georgia Institute of Technology  Atlanta Georgia 30332 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,8]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP277254"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005231"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094713"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep22930"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01097.2011"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/10739680600893909"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00677.2012"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14345"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04878.x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/10739680490476033"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.016642"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.04.006"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2016.0061"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002722"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00318.2015"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00342.2014"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2006.09.024"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1508330112"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1116152108"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-014-9416-7"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2017.0001"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1976.sp011557"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:BREA.0000032978.67677.9f"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041126"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.130401"},{"key":"e_1_2_5_27_1","unstructured":"MukherjeeA HooksJ&DixonJB(2018).Physiology: lymph flow. InLymphedema ed.LeeB\u2010B RocksonSG&BerganJ pp.91\u2013111.Springer International Publishing Cham. Available at:https:\/\/doi.org\/10.1007\/978\u20103\u2010319\u201052423\u20108_8."},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42142-9"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25383-y"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00369.2013"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0493-1"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13239-011-0054-6"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1089\/mab.2015.0041"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04867.x"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1413.010"},{"key":"e_1_2_5_36_1","first-page":"144","article-title":"Tissue fluid pressure and flow in the subcutaneous tissue in lymphedema \u2010 hints for manual and pneumatic compression therapy","volume":"17","author":"Olszewski WL","year":"2010","journal-title":"Phlebolymphology"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/GOX.0000000000000154"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00185.2013"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00322.2008"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00258.2006"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvsv.2019.01.002"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.soncn.2012.11.002"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(00)00727-0"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-017-1934-z"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2382"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.103.6.2787"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(01)00150-8"},{"key":"e_1_2_5_48_1","first-page":"188","article-title":"Intermittent pneumatic compression acts synergistically with manual lymphatic drainage in complex decongestive physiotherapy for breast cancer treatment\u2010related lymphedema","volume":"42","author":"Szolnoky G","year":"2009","journal-title":"Lymphology"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2010.12.027"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep19817"},{"key":"e_1_2_5_51_1","first-page":"113","article-title":"Influence of age and gender on human lymphatic pumping pressure in the leg","volume":"44","author":"Unno N","year":"2011","journal-title":"Lymphology"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00215"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1117\/1.JBO.17.6.066019"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46797-2"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070703"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2013.0016"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2009.0007"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1993.264.4.H1283"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00664.2015"},{"key":"e_1_2_5_60_1","first-page":"54","article-title":"Mouse tail models of secondary lymphedema: fibrosis gradually worsens and is irreversible","volume":"13","author":"Zhou C","year":"2020","journal-title":"Int J Clin Exp Pathol"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP281206","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP281206","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1113\/JP281206","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP281206","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T12:02:42Z","timestamp":1692878562000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP281206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,8]]},"references-count":59,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1113\/JP281206"],"URL":"https:\/\/doi.org\/10.1113\/jp281206","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,8]]},"assertion":[{"value":"2021-01-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}