Abstract
The lymphatic system performs important roles in various essential body functions, such as fluid homeostasis, trafficking of immune cells, and intestinal lipid absorption. Despite its important roles, the lymphatic system of the heart has largely been overlooked due to its grossly invisible nature. The cardiac lymphatic system plays important roles in myocardial fluid homeostasis, controlling inflammation and infection. Because this system can contribute to various stages of myocardial infarction and inflammation, the study of this lymphatic system can elucidate the pathologic process of many cardiovascular diseases. Also, the role of the cardiac lymphatic system should be considered in the management of patients with cardiac diseases with increased risk of myocardial edema such as myopericarditis or heart failure. In this chapter, we discuss how the cardiac lymphatic system can contribute to the regulation of cardiovascular disease and provide potential therapeutic applications related to this important network of vessels.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Mehlhorn U, Geissler HJ, Laine GA, Allen SJ (2001) Role of the cardiac lymph system in myocardial fluid balance. Eur J Cardiothorac Surg 20:424–427
Shimada T, Morita T, Oya M, Kitamura H (1990) Morphological studies of the cardiac lymphatic system. Arch Histol Cytol 53(Suppl):115–126
Johnson RA, Blake TM (1966) Lymphatics of the heart. Circulation 33:137–142
Riquet M, Hidden G (1991) Lymphatic drainage of the left atrium and ventricle of the heart. Surg Radiol Anat 13:238–240
Riquet M, Hidden G (1991) Lymphatic drainage of the right atrium and ventricle of the heart. Surg Radiol Anat 13:235–237
Miller AJ, DeBoer A, Pick R, Van Pelt L, Palmer AS, Huber MP (1988) The lymphatic drainage of the pericardial space in the dog. Lymphology 21:227–233
Leeds SE, Uhley HN, Meister RB, McCormack KR (1977) Lymphatic pathways and rate of absorption of 131I-albumin from pericardium of dogs. Lymphology 10:166–172
Miller AJ, Pick R, Katz LN (1964) The importance of the lymphatics of the mammalian heart: experimental observations and some speculations. Circulation 29(Suppl):485–487
Sun SC, Lie JT (1977) Cardiac lymphatic obstruction: ultrastructure of acute-phase myocardial injury in dogs. Mayo Clin Proc 52:785–792
Ludwig LL, Schertel ER, Pratt JW et al (1997) Impairment of left ventricular function by acute cardiac lymphatic obstruction. Cardiovasc Res 33:164–171
Wang YL, Wang XH, Liu YL, Kong XQ, Wang LX (2009) Cardiac lymphatic obstruction impairs left ventricular function and increases plasma endothelin-1 and angiotensin II in rabbits. Lymphology 42:182–187
Ishikawa Y, Akishima-Fukasawa Y, Ito K et al (2007) Lymphangiogenesis in myocardial remodelling after infarction. Histopathology 51:345–353
Feola M, Glick G (1975) Cardiac lymph flow and composition in acute myocardial ischemia in dogs. Am J Physiol 229:44–48
Park JH, Yoon JY, Ko SM et al (2011) Endothelial progenitor cell transplantation decreases lymphangiogenesis and adverse myocardial remodeling in a mouse model of acute myocardial infarction. Exp Mol Med 43:479–485
Miller AJ, Pick R, Johnson PJ (1971) The production of acute pericardial effusion: the effects of various degrees of interference with venous blood and lymph drainage from the heart muscle in the dog. Am J Cardiol 28:463–466
Miller AJ, Pick R, Kline IK, Katz LN (1964) The susceptibility of dogs with chronic impairment of cardiac lymph flow to staphylococcal vagular endocarditis. Circulation 30:417–424
Kondo T, Kitazawa R, Kawata E, Mori K, Kitazawa S (2009) Diffuse cardiac lymphatic involvement by metastatic neuroendocrine carcinoma mimicking hypertrophic cardiomyopathy: a case report. Cases J 2:9127
Uhley HN, Leeds SE, Sampson JJ, Friedman M (1969) The cardiac lymphatics in experimental chronic congestive heart failure. Proc Soc Exp Biol Med 131:379–381
Kong XQ, Wang LX, Kong DG (2007) Cardiac lymphatic interruption is a major cause for allograft failure after cardiac transplantation. Lymphat Res Biol 5:45–47
Noto N, Okada T, Abe Y et al (2012) Characteristics of earlier atherosclerotic involvement in adolescent patients with Kawasaki disease and coronary artery lesions: significance of gray scale median on B-mode ultrasound. Atherosclerosis 222:106–109
He Y, Rajantie I, Ilmonen M et al (2004) Preexisting lymphatic endothelium but not endothelial progenitor cells are essential for tumor lymphangiogenesis and lymphatic metastasis. Cancer Res 64:3737–3740
Karpanen T, Egeblad M, Karkkainen MJ et al (2001) Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res 61:1786–1790
Karkkainen MJ, Haiko P, Sainio K et al (2004) Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol 5:74–80
Nagy JA, Vasile E, Feng D et al (2002) Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med 196:1497–1506
Cao R, Bjorndahl MA, Gallego MI et al (2006) Hepatocyte growth factor is a lymphangiogenic factor with an indirect mechanism of action. Blood 107:3531–3536
Salven P, Mustjoki S, Alitalo R, Alitalo K, Rafii S (2003) VEGFR-3 and CD133 identify a population of CD34+ lymphatic/vascular endothelial precursor cells. Blood 101:168–172
Maruyama K, Ii M, Cursiefen C et al (2005) Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages. J Clin Invest 115:2363–2372
Religa P, Cao R, Bjorndahl M, Zhou Z, Zhu Z, Cao Y (2005) Presence of bone marrow-derived circulating progenitor endothelial cells in the newly formed lymphatic vessels. Blood 106:4184–4190
Kerjaschki D, Huttary N, Raab I et al (2006) Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants. Nat Med 12:230–234
Lee JY, Park C, Cho YP et al (2010) Podoplanin-expressing cells derived from bone marrow play a crucial role in postnatal lymphatic neovascularization. Circulation 122:1413–1425
Mehlhorn U, Davis KL, Burke EJ, Adams D, Laine GA, Allen SJ (1995) Impact of cardiopulmonary bypass and cardioplegic arrest on myocardial lymphatic function. Am J Physiol 268:H178–H183
Ullal SR, Kluge TH, Gerbode F (1972) Functional and pathologic changes in the heart following chronic cardiac lymphatic obstruction. Surgery 71:328–334
Gloviczki P, Solti F, Szlavy L, Jellinek H (1983) Ultrastructural and electrophysiologic changes of experimental acute cardiac lymphostasis. Lymphology 16:185–192
Witte MH, Dumont AE, Clauss RH, Rader B, Levine N, Breed ES (1969) Lymph circulation in congestive heart failure: effect of external thoracic duct drainage. Circulation 39:723–733
Laine GA, Allen SJ (1991) Left ventricular myocardial edema. Lymph flow, interstitial fibrosis, and cardiac function. Circ Res 68:1713–1721
Szlavy L, Koster K, de Courten A, Hollenberg NK (1987) Early disappearance of lymphatics draining ischemic myocardium in the dog. Angiology 38:73–84
Santos AC, de Lima JJ, Botelho MF et al (1998) Cardiac lymphatic dynamics after ischemia and reperfusion–experimental model. Nucl Med Biol 25:685–688
Kholova I, Dragneva G, Cermakova P et al (2011) Lymphatic vasculature is increased in heart valves, ischaemic and inflamed hearts and in cholesterol-rich and calcified atherosclerotic lesions. Eur J Clin Invest 41:487–497
Miller AJ, Pick R, Katz LN (1960) Ventricular endomyocardial pathology produced by chronic cardiac lymphatic obstruction in the dog. Circ Res 8:941–947
Symbas PN, Schlant RC, Gravanis MB, Shepherd RL (1969) Pathologic and functional effects on the heart following interruption of the cardiac lymph drainage. J Thorac Cardiovasc Surg 57:577–584
Weis M, von Scheidt W (1997) Cardiac allograft vasculopathy: a review. Circulation 96:2069–2077
Allen SJ, Geissler HJ, Davis KL et al (1997) Augmenting cardiac contractility hastens myocardial edema resolution after cardiopulmonary bypass and cardioplegic arrest. Anesth Analg 85:987–992
Lopez B, Querejeta R, Gonzalez A, Sanchez E, Larman M, Diez J (2004) Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure. J Am Coll Cardiol 43:2028–2035
Cui Y (2010) The role of lymphatic vessels in the heart. Pathophysiology 17:307–314
Cui Y (2010) Impact of lymphatic vessels on the heart. Thorac Cardiovasc Surg 58:1–7
Szlavy L, Adams DF, Hollenberg NK, Abrams HL (1980) Cardiac lymph and lymphatics in normal and infarcted myocardium. Am Heart J 100:323–331
Cairns JA, Holder DA, Tanser P, Missirlis E (1982) Intravenous hyaluronidase therapy for myocardial infarction in man: double-blind trial to assess infarct size limitation. Circulation 65:764–771
Roberts R, Braunwald E, Muller JE et al (1988) Effect of hyaluronidase on mortality and morbidity in patients with early peaking of plasma creatine kinase MB and non-transmural ischaemia. Multicentre investigation for the limitation of infarct size (MILIS). Br Heart J 60:290–298
Saltissi S, Robinson PS, Coltart DJ, Webb-Peploe MM, Croft DN (1982) Effects of early administration of a highly purified hyaluronidase preparation (GL enzyme) on myocardial infarct size. Lancet 1:867–871
Repa I, Garnic JD, Hollenberg NK (1990) Myocardial infarction treated with two lymphagogues, calcium dobesilate (CLS 2210) and hyaluronidase: a coded, placebo-controlled animal study. J Cardiovasc Pharmacol 16:286–291
Szlavy L, Repa I, Lengyel I, Lamboy L (1990) Calcium dobesilate (CLS 2210) protects the myocardium in early acute myocardial infarction: a preliminary randomized, double-blind, placebo-controlled study of its effects on biochemical markers. J Cardiovasc Pharmacol 15:89–95
Johnsson C, Hallgren R, Elvin A, Gerdin B, Tufveson G (1999) Hyaluronidase ameliorates rejection-induced edema. Transpl Int 12:235–243
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Park, JH., Jeong, JO. (2013). Therapeutic Applications Targeting the Cardiac Lymphatics in Heart Disease. In: Karunamuni, G. (eds) The Cardiac Lymphatic System. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6774-8_6
Download citation
DOI: https://doi.org/10.1007/978-1-4614-6774-8_6
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-6773-1
Online ISBN: 978-1-4614-6774-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)