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Despite that, the lymphatic system has been relatively neglected as a potential drug target and a source of adverse effects from CV drugs. Like the heart, the lymphatic vessels undergo phasic contractions to promote lymph flow against a pressure gradient. Dysfunction or failure of the lymphatic pump results in fluid imbalance and tissue oedema. While this can be due to drug effects, it is also a feature of breast cancer-associated lymphoedema, chronic venous insufficiency, congestive heart failure, and acute systemic inflammation. There are currently no specific drug treatments for lymphatic pump dysfunction in clinical use despite the wealth of data from pre-clinical studies. The aim of this study was to identify (i) drugs with direct effects on lymphatic tonic and phasic contractions with potential for clinical application, and (ii) drugs in current clinical use that have a positive or negative side effect on lymphatic function. We comprehensively reviewed all studies that tested the direct effect of a drug on the contractile function of lymphatic vessels. Of the 208 drugs identified from 193 studies, about a quarter had only stimulatory effects on lymphatic tone, contraction frequency, and\/or contraction amplitude. Of Food and Drug Administration-approved drugs, there were 14 that increased lymphatic phasic contractile function. The most frequently used class of drugs with inhibitory effects on lymphatic pump function were the calcium channels blockers. This review highlights the opportunity for specific drug treatments of lymphatic dysfunction in various disease states and for avoiding adverse drug effects on lymphatic contractile function.<\/jats:p>","DOI":"10.1093\/cvr\/cvab279","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T11:48:45Z","timestamp":1629287325000},"page":"2437-2457","source":"Crossref","is-referenced-by-count":36,"title":["Lymphatic contractile function: a comprehensive review of drug effects and potential clinical application"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7059-6618","authenticated-orcid":false,"given":"Peter S","family":"Russell","sequence":"first","affiliation":[{"name":"Applied Surgery and Metabolism Laboratory, School of Biological Sciences, University of Auckland , 3A Symonds Street, Private Bag 92019, Auckland Central, Auckland 1142 , New Zealand"},{"name":"Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland , Auckland , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0936-3281","authenticated-orcid":false,"given":"Jiwon","family":"Hong","sequence":"additional","affiliation":[{"name":"Applied Surgery and Metabolism Laboratory, School of Biological Sciences, University of Auckland , 3A Symonds Street, Private Bag 92019, Auckland Central, Auckland 1142 , New Zealand"},{"name":"Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland , Auckland , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie L","family":"Trevaskis","sequence":"additional","affiliation":[{"name":"Drug Delivery, Disposition andDynamics, Monash Institute of Pharmaceutical Sciences, Monash University , Parkville, Victoria , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-5432","authenticated-orcid":false,"given":"John A","family":"Windsor","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2157-0825","authenticated-orcid":false,"given":"Niels D","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6143-5866","authenticated-orcid":false,"given":"Anthony R J","family":"Phillips","sequence":"additional","affiliation":[{"name":"Applied Surgery and Metabolism Laboratory, School of Biological Sciences, University of Auckland , 3A Symonds Street, Private Bag 92019, Auckland Central, Auckland 1142 , New Zealand"},{"name":"Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland , Auckland , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"2022101813274293400_cvab279-B1","first-page":"H706","article-title":"Some consequences of capillary permeability to macromolecules: Starling's hypothesis reconsidered","volume":"250","author":"Renkin","year":"1986","journal-title":"Am J Physiol"},{"key":"2022101813274293400_cvab279-B2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.pathophys.2009.09.002","article-title":"Hydrodynamic regulation of lymphatic transport and the impact of 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