An Acupoint-Originated Human Interstitial Fluid Circulatory Network

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An Acupoint-Originated Human Interstitial Fluid Circulatory Network

Traditional Chinese medicine (TCM) has a long history, and acupoints and meridians are important concepts within it. Since 1027, when the Tian Sheng Bronze Statue showing acupoints and meridians was introduced, it has evolved into the currently used acupoints and meridians atlas in TCM. In TCM, an acupoint is seen as a gateway for substances or bio-signals to enter or escape the meridians. But in modern medical science, the anatomical structures of main meridians remain largely unclear.

Explorations of Fluid Flow from an Acupoint

  • Early Studies: In the early 1960s, by hypodermic injection of a colored dye into animal acupoints, “Bonghan ducts” were claimed as conduit-like structures for fluid flow. Since the 1990s, these were re-investigated and renamed “primo-vessels” or “primo vascular system”. However, their anatomical and histological structures remained ambiguous, and the relationship with human acupoints was unclear.
  • Isotopic Tracer Studies: In the 1950s – 1990s, hypodermic injection of an isotopic tracer into human acupoints (hands or feet) allowed visualization of long – distance migration channels by radionuclide imaging. Meng et al found that the isotopic tracer (technetium – 99m) migrated long distances in limbs. The radiotracer migration channels from acupoints were distinct from non – acupoint and non – meridian points, and also different from intravenously injected isotopes and lymphotropic isotopes. This suggested an interstitial fluid (ISF) flow pathway rather than a conduit – like vessel. But there was a lack of comprehensive data for all acupoints on meridian lines, and histological structures couldn’t be clearly identified due to poor spatial resolution of scintigraphic images.
  • MRI Studies: Since 2006, contrast – enhanced magnetic resonance imaging (MRI) was used. Hypodermic injection of a paramagnetic tracer (gadolinium diethylene – triamine pentaacetic acid [Gd – DTPA]) into acupoints visualized two types of long – distance fluid flow pathways: smooth (continuous trajectory) and non – smooth (discontinuous trajectory). Neither colocalized with lymphatic vessels. If the injection point was an acupoint, both types could be observed; if not (near a vein), only smooth. But they didn’t totally match the 12 main meridian lines on the atlas.

Identifying ISF Pathways from an Acupoint

  • Ex Vivo Human Leg Sample: In a patient with severe foot gangrene, a fluorescent tracer was injected into the Kunlun acupoint before lower leg amputation. Dissection revealed four types of ISF flow pathways:
    • Cutaneous pathway (dermis and hypodermis).
    • Perivascular and adventitial connective tissues (PACT) pathway along venous vessels.
    • PACT pathway along arterial vessels.
    • Neural pathway (endoneurium, perineurium, and epineurium of a peripheral nerve).
    • These were composed of fibrous connective tissues (not endothelial cells), confirming distinct from blood/lymph flow and a long – distance ISF flow pathway.
  • Cadaver Studies: Using a mechanical automatic chest compressor on human cadavers (simulating heart beating and chest movements), a fluorescent tracer injected into the Shaoshang acupoint (thumb) showed a cutaneous and perivenous pathway to the right atrium. The cutaneous pathway was in hand and lower forearm (not above cubital fossa), containing dermic, hypodermic, and fascial tissues from the thumb. The PACT pathway was along veins, axillary sheath, superior vena cava, and into pericardium/epicardium. Micro – CT and confocal laser microscopy showed the structure of these pathways.

Explorations of Fluid Flow in Interstitial Connective Tissues

  • Early Observations: In the 1950s – 1970s, a linear fluorescent pathway was observed along elastic fibers of interstitial connective tissues in rabbits and cats. Fluorescein transport was faster than diffusion, and elastic fibers might have a transport/guide function. It was marked as a “low – resistance” or extravascular fluid pathway.
  • Tissue Channel Studies: The regional ISF flow after deriving from capillaries was studied. The movements of marked ISF in interstitial connective tissues were named prelymphatic or interstitial tissue channels. These were believed to connect with initial lymphatic vessels, forming a random network. But the spatial structures of these tissue channels and their surroundings in the gel – like interstitial matrix for fluid flow were not well – stained and identified.

ISF Circulation via PACT Pathways

  • In Vivo Imaging and Histological Identification: ISF flow along vascular adventitia has been identified in several veins and arteries of systemic and pulmonary circulation. In rabbits, peripheral ISF in ankle dermis flowed along veins (lower extremity, inferior vena cava, into epicardium forming pericardial fluid), with velocity 3.6 – 15.6 mm/s. It also entered capillaries/lymphatic vessels and merged into blood circulation. A constant ISF flow along veins and arteries of lower limbs was observed in mice. In rabbit pulmonary circulation, ISF flowed along pulmonary vein from lung to heart.
  • Unique Spaces in PACT Pathway: In live rabbits, ISF in a venous PACT pathway flowed in at least two layers (between covering fascia and adventitia, and through adventitia). The venous adventitia had fluorescently stained fibers and gel – like matrix. The spaces for constant ISF flow were named “interfacial zone or interspace” (solid – liquid interface). The pattern was “interfacial fluid flow”. There were two patterns of constant ISF flow in venous PACT pathways: longitudinal flow and diffusion (like an irrigation system).
  • Gel Pump Hypothesis: Based on the pattern of pulling ISF from a PACT pathway and gel – like matrix characteristics, a “gel pump” was proposed. Gel – like fibrous connective tissues (e.g., covering the cardiovascular system) can act as a driver. In human cadaver and live rabbit experiments, the “gel pump” (e.g., on the heart) “pulled” peripheral ISF via PACT pathways. The one – way gel pump mechanism suggests ISF flow in interstitial connective tissue is a capillary (or interfacial fluid) flow driven by an active force.

An Acupoint – Originated Interstitial Fluid Circulatory System

  • Pathway Types in Human Body: In humans, diverse types of long – distance ISF flow pathways (cutaneous, venous PACT, arterial PACT, fascial, neural) originate from acupoints. A working hypothesis was proposed:
    • One or more ISF flow pathways (including at least one cutaneous) connect with an acupoint.
    • An ISF circulatory network is between acupoints and associated visceral organs/tissues.
    • Regulated mainly by the cardiovascular system (heart beatings and respiratory movements).
    • Part of an ISF circulatory system, communicating with other body systems.
    • Can modulate the internal environment of visceral organs/tissues from acupoints.
  • Connectome Atlas: Using a mechanical automatic chest compressor and ventilator, a network of acupoint – originated ISF flow pathways from all fingers and toes can be found in cadavers. In live human subjects, it can be visualized by enhanced or specific MRI. According to TCM’s 12 main meridians, acupoint – originated ISF flow networks can be divided into 12 groups. If “nodes” (acupoints) and “lines” (ISF flow pathways) are defined, an acupoint – originated Human Interstitial Fluid Connectome Atlas (HIFCA) can be constructed. The re – flected projections and connections can be compared with TCM atlas and meridian – organ relations.

This research, supported by various grants (Beijing Hospital Clinical Research 121 Project, National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences), provides new insights into the physiological mechanisms related to acupoints and interstitial fluid flow, potentially opening new frontiers in medical applications.

doi:10.1097/CM9.0000000000001796

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