The lymphatic system and the cardiovascular (CV) system work together to maintain body fluid homeostasis. 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.

中文翻译：

---

淋巴收缩功能：药物作用和潜在临床应用的综合综述

淋巴系统和心血管 (CV) 系统协同工作以维持体液稳态。尽管如此，淋巴系统作为潜在的药物靶点和心血管药物不良反应的来源一直被相对忽视。像心脏一样，淋巴管经历阶段性收缩以促进淋巴液逆压力梯度流动。淋巴泵功能障碍或故障会导致体液失衡和组织水肿。虽然这可能是由于药物作用，但它也是乳腺癌相关淋巴水肿、慢性静脉功能不全、充血性心力衰竭和急性全身炎症的特征。尽管来自临床前研究的大量数据，目前临床使用中没有针对淋巴泵功能障碍的特定药物治疗。本研究的目的是确定 (i) 对具有临床应用潜力的淋巴强直和阶段性收缩有直接影响的药物，以及 (ii) 目前临床使用中对淋巴功能有积极或消极副作用的药物。我们全面回顾了所有测试药物对淋巴管收缩功能的直接影响的研究。在 193 项研究中确定的 208 种药物中，约四分之一仅对淋巴张力、收缩频率和/或收缩幅度有刺激作用。在食品和药物管理局批准的药物中，有 14 种增加了淋巴阶段性收缩功能。最常用的对淋巴泵功能有抑制作用的药物是钙通道阻滞剂。