Comparative and Developmental Anatomy of Cardiac Lymphatics

Abstract

The role of the cardiac lymphatic system has been recently appreciated since lymphatic disturbances take part in various heart pathologies. This review presents the current knowledge about normal anatomy and structure of lymphatics and their prenatal development for a better understanding of the proper functioning of this system in relation to coronary circulation. Lymphatics of the heart consist of terminal capillaries of various diameters, capillary plexuses that drain continuously subendocardial, myocardial, and subepicardial areas, and draining (collecting) vessels that lead the lymph out of the heart. There are interspecies differences in the distribution of lymphatic capillaries, especially near the valves, as well as differences in the routes and number of draining vessels. In some species, subendocardial areas contain fewer lymphatic capillaries as compared to subepicardial parts of the heart. In all species there is at least one collector vessel draining lymph from the subepicardial plexuses and running along the anterior interventricular septum under the left auricle and further along the pulmonary trunk outside the heart and terminating in the right venous angle. The second collector assumes a different route in various species. In most mammalian species the collectors run along major branches of coronary arteries, have valves and a discontinuous layer of smooth muscle cells.

Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction

“…42,43 Furthermore, the remarkable improvement of cardiac function seen with our lymphangiogenic therapy is likely attributable to a combination of both direct (interstitial fluid pressure normalization) and indirect (cardiac fibrosis) effects of limiting myocardial edema. Different from lymphatic networks in other organs, 44,45 notably the essential absence of smooth muscle cells on cardiac precollectors, and only sparse muscular cells on its collecting ducts, 30 the heart largely depends on extrinsic factors for regulation of its lymphatic drainage. Consequently, cardiac contractile (systolic) dysfunction is likely a major contributing factor to the insufficient cardiac lymphatic drainage observed post-MI.…”

Anatomy and roles of lymphatics in inflammatory diseases

“…45 Myocardial plexuses form a dense basket-like network of lymphatic capillaries that can rapidly adapt to changes in their functional load. [46][47][48][49][50] Myocardial lymphatics drain to larger lymphatic channels that follow arterioles to the interstitial connective tissue septa around the epicardium. The small capillaries of the subepicardial area pass radially and connect with larger bordering capillaries to form the capillaries of the subepicardial plexus.…”

Phenotypically heterogeneous podoplanin-expressing cell populations are associated with the lymphatic vessel growth and fibrogenic responses in the acutely and chronically infarcted myocardium

“…Based on the hitherto reported data, the adult cardiac lymphatic vasculature consists of a network of sub-epicardial and sub-endocardial vessels and a plexus of myocardial capillaries of various diameters and variable concentrations in the different regions of the heart [2–4, 10, 11]. By employing immunohistochemical labeling of proteins preferentially expressed in lymphatic endothelial cells, such as lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), membrane glycoprotein podoplanin, prospero homeobox-1 (Prox-1) transcription factor, or vascular endothelial growth factor-3 (VEGFR-3), it was established that the localization and morphology of CLVs are substantially altered in pathological conditions [7–9, 11–15].…”

“…By employing immunohistochemical labeling of proteins preferentially expressed in lymphatic endothelial cells, such as lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), membrane glycoprotein podoplanin, prospero homeobox-1 (Prox-1) transcription factor, or vascular endothelial growth factor-3 (VEGFR-3), it was established that the localization and morphology of CLVs are substantially altered in pathological conditions [7–9, 11–15]. Acutely after MI, the density of CLVs increases in the early phases of wound granulation and is further elevated at later stages of tissue repair, superseding the number of blood vessels (BVs) in the scar [9, 12–15].…”