Review

Adaptive Medicine 6(2): 41-48, 2014 41DOI: 10.4247/AM.2014.ABE079

Corresponding author: Dr. Mario Bernardo-Filho, Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, fundos, 4º. andar, 20551-030, Rio de Janeiro, RJ, Brasil. Tel: +55-21-28688332, E-mail: bernardofilhom@gmail.com*World Health Organization. Acupuncture: review and analysis of controlled clinical trials. Geneva, Switzerland: World Health Organiza-tion; 2003.Received: February 15, 2014; Revised: May 5, 2014; Accepted: May 26, 2014.2014 by The Society of Adaptive Science in Taiwan and Airiti Press Inc. ISSN : 2076-944X. http://www.sast.org.tw

On the Interconnectedness of Meridian System and Zang-Fu: A Comparative Review and Its Implications

Deise Elisabete de Souza1, Daisy L.M. França2, Vasco Senna-Fernandes2, Danúbia da Cunha Sá-Caputo3, Sergio Guilhon2, Ailton Alexandre Vieira dos Santos2, Severo de Paoli4, Giuseppe Antonio Presta5, Shyang Chang6, and Mario Bernardo Filho1

1 Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofísica e Biometria, Laboratório de Radiofarmácia Experimental, Rio de Janeiro, RJ, Brasil

2Academia Brasileira de Arte e Ciência Oriental, Rio de Janeiro, RJ, Brasil3Mestrado Profissional em Saúde, Medicina Laboratorial e Tecnologia Forense, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil4Universidade Estácio de Sá, Rio de Janeiro, RJ, Brasil5Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil, and6Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan, Republic of China

In recent decades, the interest in complementary and alter- native medicine has stimulated research in various meth- odologies and approaches worldwide. Among them, acu- puncture in Traditional Chinese Medicine (TCM) has been studied by many researchers as a very efficacious and economic treatment procedure. According to the funda- mental theory of TCM, acupuncture efficacy depends heavily on the premise that diseases of visceral organs can be cured via puncturing their corresponding meridians. It is believed that the normal flow of Qi and Xue to Zang- Fu (visceral organs) can be thus restored. Hence, vali-dating the interconnectedness of Zang-Fu and meridian system is of paramount importance in clinical practice. In this review article, radiopharmaceuticals that have been used in nuclear medicine to evaluate the functions of organs are examined at first. Then, variations on the uptake of radiopharmaceuticals in different visceral or- gans of Wistar rats after acupuncture stimulation of dif- ferent meridians are compared. Trying to decipher their interconnectedness, bioavailability results of radiopharma- ceuticals in combination with the modern conceptualiza- tions of meridian system and Five-Phase theory are invoked. Finally, implications in acupuncture therapeutics and the physiology of internal organs based on the aforementioned results are conjectured. This review, hopefully, will spark more research on using acupuncture as an integrative approach in studying physiology, pathophysiology and treatment of visceral organs.

Key Words: acupuncture, Five-Phase theory, meridian system, radiopharmaceuticals, TCM, Zang-Fu

Introduction

In recent decades, there is a dramatic growth of in-terest in complementary and alternative medicine (CAM) worldwide. This new trend of integrative approach has stimulated researches on various mo-dalities of healing and healthcare related to CAM. Among the numerous CAM therapies, acupuncture of traditional Chinese medicine (TCM) has been a subject of intense interest* (21). According to TCM, the human body, just like the macrocosm, is consid- ered as a microcosm of inseparable whole. In addition, this dynamic and intrinsically coordinated body inter- acts constantly with the environment (8). Based on this kind of holistic natural philosophy, the physiolo-gy, pathology, diagnosis, prevention and treatment of diseases in TCM have been described in ancient time by a collection of terse concepts such as Qi, Ying- Yang, and Five-Phases etc. due to lack of mathemati- cal machinery. To describe the microcosm and its complex dynamical interactions with the macrocosm, it is understandable that such a description of holistic natural philosophy is too primitive. Rigorous mathe- matical representation and modern characterization are required to avoid misinterpretation and misunder- standing.

An emerging theory of meridian system and acupuncture mechanism that can explain conclusively why acupuncture is efficacious in treating various kinds of diseases has been proposed recently (8-11). It is

42 de Souza, França, Senna-Fernandes, Sá-Caputo, Guilhon, dos Santos, de Paoli, Presta, Chang and Bernardo-Filho

based on a so-called “chaotic wave theory of fractal continuum” which was intended for a modern in-terpretation of ancient Chinese natural philosophy. When this theory is applied to TCM, the meridian system can be deciphered as a self-similar complex network of neurovascular bundles and smaller branches which connect internally with the viscera or Zang-Fu, and externally with the limbs and sensory organs. Basically, it is believed that either the mac-rocosm or the microcosm is a continuum with fractal structure and their components would interact among themselves in terms of chaotic waves. As to the mech- anism of acupuncture therapeutics, this theory of meridian system conjectures that the neurovascular bundles actually connect internally with the visceral organs and brain so that the stimulation of meridian which may be far away from the locations of symp-toms can yet treat the diseases via adjusting the im- pedances of the interconnected neurovascular bundles. This plausible theory is partially based on the concrete experiments of squid giant axon in neuroscience and the vascular system of dogs in hemodynamics. It, so far, has been very successful in explaining the mech-anisms of acupuncture analgesia and therapeutics of various diseases (10, 11). For instance, blepharitis in the eyelids can be satisfactorily treated by acupunc-turing in the feet (3). Moreover, the same principle can be used to unify the mechanism of French au-riculotherapy with that of Chinese acupuncture (2). Yet, in order to understand fully Zang-Fu on one hand, and their relationships with meridian system on the other hand, more concrete experiments are imperative. After all, their relationship can help acupuncturists decide which meridians to choose when dealing with diseases of various visceral organs in clinical practice.

Recall that in the reference No. 9, it was men- tioned that nuclear tracers used to track the indi- vidual trajectory of acupuncture meridians in both humans and animals were not very successful. How- ever, radiopharmaceuticals used in nuclear medicine (4, 5, 12, 14, 20, 22, 25, 26, 31, 32, 36) can be very useful in studying the relationship between merid-ian system and Zang-Fu in vivo and in vitro (6, 23, 27-30, 33-35, 40). Variations on the uptake of a ra-diopharmaceutical in an organ may help reveal the important connection between them. In this review paper, it will be firstly examined the relevance of radiopharmaceuticals that have been used in nuclear medicine. Then, variations on the uptake of a radio- pharmaceutical in visceral organs of Wistar rats after puncturing specific acupoints of related meridian will be used to examine the interconnectedness between meridian system and Zang-Fu. Finally, the combina- tion of (i) bioavailability results provided by the use of specific radiopharmaceuticals in controlled experi- ments after the stimulation of acupoint with needle

and (ii) modern conceptualizations of meridian system and Five-Phases theory based on the chaotic wave theory of fractal continuum will be able to help us illu- minate, at least partially, their interconnectedness.

Radiopharmaceuticals in Nuclear Medicine

In nuclear medicine, radionuclides that are used to label cellular or molecular structures with biological interest are called radiopharmaceuticals (26). They are used to study the physiology and pathology asso-ciated with organs or systems so as to aid in the di-agnosis and/or treatment of diseases. Investigations about the blood flow, metabolism and morphology of a target in organism (25, 26, 32) through in vivo and in vitro investigations have been carried out (4-6, 12, 14, 20, 22, 23, 27-31, 33-36, 40). Variations on the uptake of a radiopharmaceutical in a specific organ may be related to its pathological conditions or normal physiological response due to certain outside stimula- tion. Single photon emission computerized tomography (SPECT) and positron emission tomography (PET) are two modalities of conventional nuclear medicine im-ages. Technetium-99m (99mTc) is the main radionu-clide used to get 99mTc-radiopharmaceuticals used in SPECT while fluorine-18 (18F) is mostly used in the preparation of PET-radiopharmaceuticals (25, 26). The 99mTc, as sodium pertechnetate, is milked from 99mTc/99Molibidenium generator, and in this chemical form it is used in clinical studies and researches. Under controlled conditions, this salt is utilized to get many 99mTc-radiopharmaceuticals (26). 99mTc-methylene- diphosphonic (99mTc-MDP) and 99mTc-sodium pertech- netate (Na99mTcO4) are two widely used radiopharma- ceuticals in the nuclear medicine (25, 26).

For instance, the Na99mTcO4 in clinical nuclear medicine is applied to study the thyroid and detect gastrointestinal clinical conditions such as intestinal hemorrhages, Merckel’s diverticulum disease, and ectopic gastric tissues (4, 26, 32). The pertechnetate anion is distributed throughout the vasculature and interstitial fluids by a slow diffusion mechanism and it is also concentrated in various organs including stomach and intestines (26). However, the bioavailability of Na99mTcO4 can be changed under many circumstances by intrinsic factors, such as blood flow, capillary permea- bility, membrane transport, intracellular interactions, biotransformation and others (26, 32).

The 99mTc-MDP, on the other hand, is used to identify bone areas mainly due to its strong affinity of hydroxyapatite crystals present in the mineral phase of the bone with the diphosphonate compounds (5, 20, 26, 31, 36). Its quantitative measurements in bone would also reflect blood flow and osteoblastic activity (26). The differential accumulation of the radiophar- maceutical is related to diseased tissue on the basis of

Interconnectedness of Meridian System and Zang-Fu 43

perfusion (5, 31). Furthermore, bone scintigraphy with 99mTc-MDP is a method in evaluating patients with chronic low back pain, and it is useful in identifying a broad range of diseases including skeletal metas-tases, fractures, spondylolysis, osteoid osteomas and sacroilitis (7, 20, 31, 36).

Radiopharmaceuticals in Acupuncture

Various methods, such as those used in nuclear medicine, have been utilized to obtain scientific evidence of TCM. In particular, the use of radiop-harmaceuticals has been adopted to obtain scientific information about the clinical effects of TCM (6, 23, 27, 33, 40). For instance, Souza et al. (33) have pub- lished a review about the use of nuclear medicine methodologies to assess acupuncture effects. In that review, the use of PET and SPECT after the stimula- tion of some important and frequently used acupoints is reported. The treatments of diseases and relevant clinical findings have also been indicated. The aim of this review, in the following, is to reveal findings in controlled studies of Wistar rats by our research group according to the variations of uptake in radio- pharmaceuticals of visceral organs so as to understand their interconnectedness with the meridian system in the theories of acupuncture and TCM.

In Table 1, the selected papers involving the up- take of radiopharmaceuticals in Zang-Fu organs are shown (28-30, 34, 35). From this Table, it is possible to see the radiopharmaceuticals used, acupoints stimu- lated, and types of stimulations adopted.

General Experimental Method

In order to illustrate clearly the procedures used in the papers of Table 1, the general experimental method in studying the interconnectedness of meridian sys-tem and Zang-Fu via the bioavailability of a radio-

pharmaceutical under acupuncture will be provided next. Firstly, as indicated in Fig. 1, the animals were separated into two groups: the control group (CG) and experimental group (EG). While the animals of CG were not treated with acupuncture, the animals of EG were needled in specific acupoints. After the administration of a radiopharmaceutical, the animals were later sacrificed and the organs isolated. The radio- activity was counted in each organ and the percentage of the injected dose (%ID) determined. Afterwards, statistical analysis was performed to compare the %ID in the CG and EG.

Manual Stimulation of Stomach-36 (ST36 or Zusanli) and Its Effects on Wistar Rats

ST36 of the Stomach Meridian is one of the most fre-

Table 1. Publications involving the acupoints, types of stimulation, and uptakes of radiopharmaceuticals in Zang-Fu

Publication Radiopharmaceutical Acupoint Type of the stimulation Reference

Acupunct. Electrother. Res. 31:33-44, 2006.

Sodium pertechnetate Zusanli(ST36)

Manual 28

Am. J. Chinese Med. 35:977-986, 2007.

Sodium pertechnetate Sanyinjiao(SP6)

Manual 34

J. Acupunct. Meridian Stud. 2:135-146, 2009

Sodium pertechnetate Zusanli(ST6)

Electric 29

Evid. Based. Complement. Alternat. ed. 2011; 2011:823941

Sodium pertechnetate Zusanli (ST36) and Sanyinjiao (SP6)

Manual 30

Med. Acupunct. 23:93-99, 2011 99mTc-methylenediphosphonate Taixi (KI3) Manual 35

Fig. 1. General experimental method in studying the intercon-nectedness of meridian system and Zang-Fu via the bio- availability of a radiopharmaceutical under acupuncture.

Wistar rats

Administration of the radiopharmaceutical

Animals sacrificed and the organs isolated

Radioactivity determined in each organ

Statistical analysis to comparet the %ID in the CG and EG

Determination of the percentage of injected dose (%ID) in organ

Insertion of needle in the acupointNo treatment

Experimental group - EGControl group - CG

44 de Souza, França, Senna-Fernandes, Sá-Caputo, Guilhon, dos Santos, de Paoli, Presta, Chang and Bernardo-Filho

quently used and studied acupoints in TCM due to a substantial history of its beneficial claims. Lu et al. (18) reported that the therapeutic potential of ST36 may be related to the high concentration of larger-than-normal proportion of A-β afferent fibers at the site of this point in rats, containing more myelinated fibers compared to other non-acupoints sites. The loca- tion of ST-36 is 3-cun below the knee, 3-cun below Dubai (ST-35), one finger breadth lateral to the ante-rior crest of the tibia, in tibialis anterior muscle (29, 38). In clinical research, ST36 has been used suc-cessfully to study the (a) regulatory effects on gas-trointestinal tract function that can either strengthen the contraction and digestive function of a weak stomach or relax the spasms of a stressed stomach, (b) alleviations of abdominal pain and spasms related to the stomach, kidneys or gallbladder, and (c) other clinical conditions (7, 16, 39). Stimulating ST36 was also found to be highly beneficial for reducing cancer cell te- lomere to practically zero for malignant tumors includ- ing brain tumors. In animal studies, the acupuncture stimulation at ST36 is frequently used to study acu-puncture effects on various physiological regulatory mechanisms and control systems changes, such as pain control, gastrointestinal, cardiovascular or neurologi- cal activities, immunological response, and others (7, 16, 24, 38).

The effects of acupuncture on the bioavailability of the radiopharmaceutical Na99mTcO4 in Wistar rats have been investigated with manual stimulation (28). The animals of the experimental group were treated by inserting stainless steel needles bilaterally at ST36 point. For comparison, the animals of the control group were untreated. The radiopharmaceutical Na99mTcO4 (3.7MBq) was then administered in each animal of the experimental group by the ocular plexus 10 min after every needle insertion. The rats were sacrificed 25 min later, their organs were then isolated and the radioactivity in each organ was determined by a well gamma counter. The percentage of injected radiop-harmaceutical dose per gram of tissue (%ID/g) was assessed for each organ as follows. The %ID/g has in-creased significantly (P < 0.05) from the control group to experimental group in pancreas (from 0.15 ± 0.03 to 0.91 ± 0.17), stomach (from 3.51 ± 0.22 to 7.98 ± 0.69), spleen (from 0.42 ± 0.15 to 0.99 ± 0.11), brain (from 0.09 ± 0.04 to 0.19 ± 0.09), lung (from 0.85 ± 0.15 to 1.89 ± 0.29), liver (from 0.61 ± 0.03 to 1.29 ± 0.10), kidneys (from 0.15 ± 0.03 to 0.91 ± 0.17), heart (from 0.31 ± 0.02 to 0.81 ± 0.17) and testis (from 0.14 ± 0.03 to 0.47 ± 0.01). The details can be obtained in Senna-Fernandes et al., 2006 (25). The amount of radiopharmaceutical in stomach has increased the most even though the ratio of increase is about the same as that of other visceral organs after stimulation of Zusanli.

Manual Stimulation of Spleen-6 (SP6 or Sanyinjiao) and Its Effects on Wistar Rats

SP6 of the Spleen Meridian is another acupoint that has been widely used and studied in acupuncture. It is located in the posterior border of the tibia, 0.5 mm above the medial malleolus. It is also an important tonification acupoint for many disorders, such as gy-necological, genitourinary, allergic, immunological and psychosomatic diseases, insomnia, and pain con-trol (15, 38). For instance, acupuncture at SP6 has been shown to reduce acetic-acid-induced visceral nociception, it can also inhibit glutamate-induced noci- ception, as well as both neurogenic and inflammatory nociceptive responses induced by injection of forma- lin in mice.

An important investigation (34) was carried out to evaluate the effect of end-organ response induced by acupuncture in the acupoint SP6 on the bioavail-ability of the radiopharmaceutical sodium pertech-netate in Wistar rats. Rats were randomly divided in an experimental group in which the animals were bilaterally stimulated at acupuncture point SP6 with stainless steel needles and the control group was not stimulated. Ocular plexus administration of radio-pharmaceutical was carried out 10 min after every needle insertion in all animals. Ten more min later, the animals were sacrificed and their organs were isolated. The radioactivity of the Na99mTcO4 was determined in a well gamma counter and the percentage of in- jected dose per gram of tissue (%ID/g) was determined for each organ as follows. The %ID/g was signifi-cantly reduced (P < 0.05) in the small intestine of the experimental group (0.56 ± 0.09) when compared to the control group (0.82 ± 0.18). Moreover, the %ID/g has also decreased, although not very significantly, from the control group to experimental group in pan-creas (from 0.57 ± 0.09 to 0.48 ± 0.13), stomach (from 1.60 ± 0.39 to 1.41 ± 0.27), spleen (from 0.46 ± 0.15 to 0.43 ± 0.05), kidneys (from 0.78 ± 0.12 to 0.74 ± 0.16), liver (from 0.59 ± 0.05 to 0.57 ± 0.11), heart (from 0.44 ± 0.08 to 0.41 ± 0.10) and testis (from 0.17 ± 0.03 to 0.15 ± 0.02), except for lung (from 0.81 ± 0.18 to 0.91 ± 0.12). The details can be obtained in Souza et al., 2007 (34). These numerical results suggest that the radiopharmaceutical dose per gram of visceral organs and tissues have almost all decreased in rats. Hence, one of the implications is that the amount of vascular flow to each visceral organ is possibly reduced for it is proportional to the amount of radio-pharmaceutical dose. At least, the vascular flows to visceral organs cannot be more than that of the con-trol group after stimulation of Sanyinjiao.

Incidentally, to compare the results of SP6 in the Spleen Meridian (34) with the previous results of stimu- lation in the ST36 of Stomach Meridian, the dosages

Interconnectedness of Meridian System and Zang-Fu 45

in the stomach, jejunum, ileum, cecum, transverse and rectum from the animals of the treated groups were found to have significant differences (P < 0.05) from those of the animals of the control group (28).

Manual Stimulation of Kidney-3 Acupoint (KI3 or Taixi) and Its Effects on Wistar Rats

KI3 is the third acupoint of the Kidney Meridian. It is a relatively shallow acupuncture point located on the medial aspect of the foot. Its innervation is attributed to the medial crural cutaneous nerve on the course of the tibial nerve (41). The acupoint Taixi, according to anatomical landmarks of the rat’s anatomy, is located in the depression between the medial malleolus and the tendon calcaneus (Achilles’ tendon) (41). The main indications of this acupoint are for the treatment of lower back pain (19, 37, 38), bronchial asthma (42), urogenital disorders, enuresis, dysmenorrheal, amen-orrhea, erectile dysfunction and cystitis (13, 38). Sjödgren’s syndrome (17) and the clinical manifesta-tion of darkness under the eyes and facial edema (1) can also be treated with the stimulation of this acu-point.

An experimental study (35) was used to inves- tigate the effects of stimulation of Taixi on the bioavail- ability of the radiopharmaceutical 99mTc-MDP in male Wistar rats. They were bilaterally stimulated at KI3 with stainless steel needles in the experimental group. The animals of the control group were not stimulated. Ocular plexus administration of 99mTc-MDP (7.4 MBq) was taken 10 min after needle insertion in the rats. After 180 min, the animals were sacrificed, the organs isolated, the radioactivity determined in a well gamma counter, and the percentage per gram of tissue of in- jected dose (%ID/g) was determined as follows. The %ID/g was significantly decreased (P < 0.05) in the large intestine of the rats in the experimental group (0.167 ± 0.056) as compared to control group (0.370 ± 0.142) and in bone of 0.562 ± 0.054 as to 0.873 ± 0.282 in the control group. As to the radioactivity uptakes in the %ID/g, almost all of the visceral organs have also decreased, although not very significantly, from the control group to experimental group in pancreas (from 0.024 ± 0.011 to 0.016 ± 0.005), stomach (from 0.046 ± 0.021 to 0.043 ± 0.021), spleen (from 0.059 ± 0.031 to 0.033 ± 0.007), kidneys (from 1.251 ± 0.414 to 0.925 ± 0.310), liver (from 0.036 ± 0.010 to 0.030 ± 0.013), heart (from 0.020 ± 0.004 to 0.018 ± 0.006), except for lungs (from 0.036 ± 0.014 to 0.045 ± 0.018). The details can be obtained in Souza et al., 2011 (29). These numerical results suggest that the radiopharma- ceutical dose per gram of visceral organs and tissues have almost all decreased slightly in rats, except for the lungs. Hence, one of the implications is that the amount of vascular flow to each visceral organ is clearly

reduced for it is proportional to the amount of radio pharmaceutical dose. Again, at least, the vascular flows to visceral organs cannot be more than that of the control group after stimulation of Taixi.

Electroacupuncture of Zusanli with 2 and 100 Hz and Its Effects on Wistar Rats

In an investigation (29), the bioavailability of Na99mTcO4 in rats was used to understand the effects of electroa- cupuncture at Zusanli at two different frequencies (2 and 100 Hz). Wistar rats were firstly treated by electroa-cupuncture at 2 Hz at ST36 bilaterally, and later the same site at 100 Hz bilaterally. The Na99mTcO4 (7.4 MBq) was administrated via the ocular plexus and, 20 min before sacrifice, blood was withdrawn for radio- labeling assays. In the bioavailability analysis, organs and tissues were isolated, then their radioactivity de-termined in terms of the percentage of injected dose per gram of organ or tissue (%ID/g). Whole blood was separated and then the plasma and blood cells were isolated, and the samples also precipitated with 5% trichloroacetic acid to separate the soluble and insoluble fractions of plasma and blood cells. These evaluations were assessed as percentage of injected dose (%ID) in blood (%ID/blood).

The results showed significant differences in the %ID/g in some organs and tissues in comparison with the control group to the animals submitted to electroacupuncture (2 Hz), as in spleen (from 0.67 ± 0.33 to 0.99 ± 0.24), liver (from 0.72 ± 0.29 to 1.23 ± 0.23), stomach (from 3.49 ± 1.43 to 4.23 ± 0.79), small intestine (from 0.91 ± 0.37 to 1.32 ± 0.68) and thyroid (from 5.20 ± 1.25 to 7.72 ± 2.08). These results are, however, consistent with the manual acupuncture.

Moreover, the stimulation with electroacupunture (100 Hz) shows that the treatment interferes with the uptake of the radiopharmaceutical in stomach (from 3.49 ± 1.43 to 6.59 ± 2.12), urinary-bladder (from 1.50 ± 0.74 to 2.59 ± 0.94) and thyroid (from 5.20 ± 1.25 to 8.84 ± 1.01). These results are also consistent with the manual acupuncture. However, in the blood labeling analyses, electroacupunture at 2 Hz significantly in-creased the fixation on the insoluble fraction of the blood cells (P < 0.0001) from 34.57 ± 7.29 to 70.43 ± 3.17 and electroacupunture at 100 Hz significantly in- creased this fixation from 34.57 ± 7.29 to 62.22 ± 10.98.

Interconnectedness of Zang-Fu and Meridian System and Its Clinical Implications

In order to explain the variations on the uptake of ra- diopharmaceuticals in different visceral organs of rats after acupuncture stimulation of different meridians, modern conceptualizations of meridian system and Five- Phase theory are required. The new characterizations

46 de Souza, França, Senna-Fernandes, Sá-Caputo, Guilhon, dos Santos, de Paoli, Presta, Chang and Bernardo-Filho

of these ancient concepts are essentially based on a recently proposed “chaotic wave theory of fractal con- tinuum” originally intended for the modern interpreta- tion of ancient Chinese natural philosophy. Recall in Part 1 of the review series (8, 9), the general concepts of Qi, Yin-Yang and Five-Phases in the Chinese na- tural philosophy were characterized in terms of modern dynamical systems. First of all, Qi could be defined as a dynamical system and then Yin-Yang as a hyperbolic flow on the dynamical system. Finally, the concept of Five-Phases could be defined as the Markov parti- tion of dynamical system under this Yin-Yang hyper- bolic map. That hyperbolic flow was topologically semi-conjugate to the sub-shift of finite type deter-

mined by a transition matrix

0 1 1 1 00 1 1 1 00 1 1 1 01 0 0 0 11 0 0 0 1

A

. The

symbolic dynamics associated with A, a sub-shift of finite types, is very useful in describing the intercon-nectedness of Zang-Fu visceral organs. In one ap-plication, for instance, the rows and columns of this 5 by 5 transition matrix A can represent the admissi-bility of one-step transition of vascular flows among the Five-Phases, i.e., heart, spleen, kidney, liver, and lung in sequential order, respectively. For example, the entry A12 in the transition matrix is equal to 1 and it would represent that vascular flow from heart to spleen is admissible in one-step or within one-cycle of the systemic circulation. By the same token, A41 is also equal to 1 and it would represent that the back vascular flow from liver to heart is also admissible within one-cycle of systemic circulation. However, the value of A52 is 0 and that would indicate the vascular flow directly from lung to spleen within one-cycle is not admissible. Hence, the state transition matrix A would be able to generate admissible trajectories of vascular flows among the visceral organs in terms of this kind of symbolic dynamics. Notice that A2 repre- sents the state transition of vascular flows in two-steps, i.e., systemic circulation within two complete cycles. It is clear from the matrix multiplication that no entry will be 0 after A multiplies itself more than once under normal physiological conditions. As a result, the vascular flow of Zang-Fu organs will be mixed among themselves after two cycles of systemic cir- culation. Entries will become 0’s instead of 1’s de- pending on whether the routes are blocked or not. In case of pathological conditions, certain routes of the vascular flow may be blocked and the corresponding matrix entries in that case would be set to 0’s instead of 1’s.

The meridian system, as indicated in the Intro-

duction section, is the complex network of neurovas-cular bundles and their smaller branches (8-10, 21). As a result, the blood would be properly distributed in the body according to different physiological con-ditions (8-10, 21). It is known that acupuncture at acupoints of different meridians will modify the im-pedances of that corresponding neurovascular bun-dles. Due to the magneto-electric inductive effects, it is believed that the neurovascular flows to the cor-responding Zang-Fu would also be modified. With these basic ideas in mind, one can now investigate the implications of previous experimental results.

First of all, the bioavailability of radiopharma-ceutical Na99mTcO4 in Wistar rats after stimulation at ST36 of Stomach Meridian has indicated that the uptakes of radioactivity in stomach, spleen, kidneys, liver, lung and heart in rats have all been increased (28). One of the possible reasons for the increase of bioavailability in Na99mTcO4 can be ascribed to the increase of blood flow in Zang-Fu after 10 min. It is then proper and fitting to say that the stimulation of ST36 in the Stomach Meridian can increase blood flow not only to its corresponding visceral organ stomach, but also all other visceral organs via the mixing prop- erty of Five-Phases. In clinical practice, the implica- tion could be that if somehow the vascular flow of stomach is stagnant, partially or totally blocked, then stimulation of ST36 can increase the vascular flow to stomach and treat the corresponding symptoms.

Next, the bioavailability of Na99mTcO4 in Wistar rats after stimulation at SP6 of Spleen Meridian has indicated that the uptakes of radioactivity in stomach, spleen, kidneys, liver, and heart in rats have almost all been decreased except for the lungs (34). It is quite possible that, in this case, the decrease of bio-availability in Na99mTcO4 is due to the decrease of blood flow to Zang-Fu. Hence, the stimulation of SP6 in the Spleen Meridian can decrease the blood flow to almost all visceral organs via the mixing prop- erty of Five-Phase theory. In clinical practice, the im- plication would be that if there is hemorrhage in certain visceral organ, except for the lungs, stimulation of SP6 can decrease the vascular flow to those places and stop the hemorrhage problem thereof. In particular, the decrease of bioavailability of the Na99mTcO4 in small intestine is more prominent. As indicated (11), acu- puncture may play an active role in treating cancers per se by reducing blood flow to the cancerous region firstly. Hence, in the case of cancer in small intestine, acupuncture of SP6 may provide a potential procedure for cure. By the same token, the same acupuncture pro- cedure might help cancerous patients to avoid malignant metastasis in Zang-Fu for the vascular flow to those places could be reduced. Of course, this conjecture will need more clinical observations from the cooperation of the whole medical community of the world. But,

Interconnectedness of Meridian System and Zang-Fu 47

it is worth the efforts.Then, the bioavailability of 99mTc-MDP in Wistar

rats after stimulation at KI3 of Kidney Meridian has also indicated that the uptakes of radioactivity in stomach, spleen, kidneys, liver, and heart in rats have all been decreased, except for the lungs (35). It is quite possible that, in this case, the decrease of bioavailability of the 99mTc-MDP is again due to the decrease of blood flow to Zang-Fu. Hence, the stimulation of KI3 in the Kidney Meridian can also decrease the blood flow to almost all visceral organs. In clinical practice, the implication would be that if there is hemorrhage in the visceral organ, stimulation of KI3 can decrease the vascular flow to it and cure the problem. In particular, the decreases of bioavailability in 99mTc-MDP in large intestine and bone are most prominent. Hence, in the cases of cancer of large intestine and bone, acupuncture at KI3 may provide a decrease of blood supply to those regions. As a result, it may provide a potential treat-ment for cure (11). Again, this conjecture will need more imperative clinical evidence from the medical community of the world. In the same vein, acupunc-ture at KI3 might free those cancerous patients from the fear of metastasis because the vascular flows to most of the visceral organs will be reduced.

Finally, when one looks at the results of elec-troacupuncture at ST36, most of them are consistent with those of manual acupuncture, except on the blood labeling analyses. For example, electroacupuntures at 2 and 100 Hz will both significantly increase the fixation on the insoluble fraction of the blood cells (P < 0.0001).

To recapitulate, the stimulation of “Yang” me- ridian of Stomach seems to increase the vascular flow to Zang-Fu while those “Yin” meridians of Spleen and Kidney tend to decrease vascular flows to Zang-Fu organs. The clinical implications of these results can be very important in dealing with serious problems such as cancer and its metastasis in clinical practice.

Conclusion

In TCM, meridian system is said to be interconnected with Zang-Fu. Diseases of visceral organs can be cured via puncturing their corresponding meridians for the normal neurovascular flows to Zang-Fu can be thus restored. In this review, variations on the uptake of radiopharmaceuticals in different visceral organs of Wistar rats after acupuncture stimulation of different meridians have been used to validate the premise. How- ever, to accurately decipher experimental results, modern conceptualizations of meridian system and Five-Phase theory have to be invoked. Moreover, potential clinical implications of acupuncture therapeutics have also been conjectured. In particular, it is possible to speculate

that an active role in cancer treatment that acupunc-ture can play has been emphasized. It is hoped that this review will not only (i) encourage more research on the integrative approach of acupuncture in dealing with various diseases, but also (ii) help clinicians in selecting the proper meridians when dealing with visceral diseases during their clinical practice.

Acknowledgments

This work was supported in part under grants of the CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico - National Counsel of Tech-nological and Scientific Development) and FAPERJ (Fundação Carlos Chagas Filho de Amparo à Pes-quisa do Estado do Rio de Janeiro) and UERJ.

References

1. Barrett, J.B. Acupuncture and facial rejuvenation. Aesthetic Surg. J. 25: 419-424, 2005.

2. Bernardo-Filho, M., Sá-Caputo, D.C., Marin, P.J. and Chang, S. The mechanism of auriculotherapy: a case report based on the fractal structure of meridian system. African J. Tradit. Comple-ment. Altern. Med. 11: 30-37, 2014.

3. Bernardo-Filho, M., Sá-Caputo, D.C., Pedrini, A.G. and Chang, S. Alleviation of symptoms in blepharitis with acupuncture and vibration in an oscillating platform: a case report. Adapt. Med. 6: 32-37, 2014.

4. Blackmon, K.N. and Rao, A.G. Ectopic kidney mimicking a Meckel’s diverticulum on Tc-99m pertechnetate scan. Clin. Nucl. Med. 36: e228-e230, 2011.

5. Blake, G.M., Park-Holohan, S.J., Cook, G.J.R. and Fogelman, I. Quantitative studies of bone with the use of 18F-fluoride and 99mTc- methylene-diphosphonate. Semin. Nucl. Med. 31: 28-49, 2001.

6. Campbell, A. Point specificity of acupuncture in the light of recent clinical and imaging studies. Acupunct. Med. 24: 118-122, 2006.

7. Chang, C.S., Chou, J.W., Ko, C.W., Wu, C.Y. and Chen, G.H. Cu-taneous Electrical stimulation of acupuncture points may enhance gastric myoelectrical regularity. Digestion 66: 106-111, 2002.

8. Chang, S. Physiological rhythms, dynamical diseases and acupunc- ture. Chinese J. Physiol. 53: 77-90, 2010.

9. Chang, S. The meridian system and mechanism of acupuncture- a comparative review. Part 1: the meridian system. Taiwan. J. Obstet. Gynecol. 51: 506-514, 2012.

10. Chang, S. The meridian system and mechanism of acupuncture- a comparative review. Part 2: mechanism of acupuncture analgesia. Taiwan. J. Obstet. Gynecol. 52: 14-24, 2013.

11. Chang, S. The meridian system and mechanism of acupuncture- a comparative review. Part 3: mechanisms of acupuncture therapies. Taiwan. J. Obstet. Gynecol. 52: 173-184, 2013.

12. Freitas, R.S., Moreno, S.R.F., Lima-Filho, G.L., Fonseca, A.S. and Bernardo-Filho, M. Effect of a commercial extract of Paullinia cupana (guaraná) on the binding of 99mTc-DMSA on blood con-stituents: an in vivo study. Appl. Radiat. Isot. 65: 528-533, 2007.

13. Fu, B., Lun, X. and Gong, Y. Effects of the combined therapy of acupuncture with herbal drugs on male immune infertility-a clini-cal report of 50 cases. J. Tradit. Chin. Med. 25: 186-189, 2005.

14. Gomes, M.L., Mattos, D.M., Freitas, R.S., Diré, G.F., Lima, E.A., Souza, S.M. and Bernardo-Filho M. Evaluation of the effect of mitomycin-C on the bioavaliability of technetium-99m-labelled so- dium pyrophosphate in mice. Cell. Mol. Biol. 48: 757-759, 2002.

15. Kim, J.H., Chung, J.Y., Kwon, Y.K., Kim, K.J., Yang, C.H., Hahm,

48 de Souza, França, Senna-Fernandes, Sá-Caputo, Guilhon, dos Santos, de Paoli, Presta, Chang and Bernardo-Filho

D.H., Lee, H.J., Pyun, K.H. and Shim, I. Acupuncture reduces alcohol withdrawal syndrome and c-Fos expression in rat brain. Am. J. Chinese Med. 33: 887-896, 2005

16. Kim, H.W., Kwon, Y.B., Ham, T.W., Roh, D.H., Yoon, S.Y., Lee, H.J., Han, H.J., Yang, I.S., Beitz, A.J. and Lee, J.H. Acupoint stimula-tion using bee venom formalin-induced pain behavior and spinal cord fos-expression in rats. J. Vet. Med. Sci. 65: 349-355, 2003.

17. Liu, W., Liu, B. and Zheng, H.X. Observation on therapeutic effect of acupuncture and moxibustion in 60 cases of Sjödgren syn-drome. Zhongguo Zhen Jiu 25: 101-102, 2005.

18. Lu, G.W. Characteristics of afferent fiber innervation on acupunc-ture points zusanli. Am. J. Physiol. 245: R606-R612, 1983.

19. MacPherson, H., Thorpe, L., Thomas, K. and Campbell, M. Acu-puncture for low back pain: traditional diagnosis and treatment of 148 patients in a clinical trial. Complement. Ther. Med. 12: 38-44, 2004.

20. McCarthy, E.F. Histopathologic correlates of a positive bone scan. Semin. Nucl. Med. 27: 309-320, 1997.

21. Moffet, H.H. How might acupuncture work? A systematic review of physiologic rationales from clinical trials. BMC Complement. Altern. Med. 6: 25-32, 2006.

22. Moreno, S.R.F., Silva, A.L.C., Dire, G., Honeycut, H., Carvalho, J.J., Nascimento, A.L., Pereira, M., Rocha, E.K., Oliveira-Timoteo, M., Amobio, A., Orej, B., Bernardo-Filho, M. and Caldas, L.Q.A. Ef-fect of oral ingestion of an extract of the herb Uncaria tomentosa on the biodistribution of sodium pertechnetate in rats. Braz. J. Med. Biol. Res. 40: 77-80, 2007.

23. Newberg, A.B., Lariccia, P.J., Lee, B.Y., Farrar, J.T., Ma, L.L. and Alavi, A. Cerebral blood flow effects of pain and acupuncture: a preliminary single-photon emission computed tomography imag-ing study. J. Neuroimaging 15: 43-49, 2005.

24. Omura, Y., Shimotsura, Y., Ooki, M. and Noguchi, T. Estimation of the amount of telomere molecules in different human age groups and the telomere increasing effect of acupuncture and shiatsu on St.36, using synthesized basic units of the human telomere mol-ecules as reference control substances for the bi-digital O-ring test resonance phenomenon. Acupunct. Electrother. Res. 23: 185-206, 1998.

25. Perkins, A.C. Tumour imaging and therapy. In: The Cancer Clock. UK: edited by Missailidis, S., Wiley & Sons. 2007; pp. 135-157.

26. Saha, G.B. Fundamentals of nuclear pharmacy, New York: Springer Verlag, 2010.

27. Schlünzen, L., Vafaee, M.S. and Cold, G.E. Acupuncture of LI-4 in anesthetized healthy humans decreases cerebral blood flow in the putamen measured with positron emission tomography. Anesth. Analg. 104: 308-311, 2007.

28. Senna-Fernandes, V., França, D., Moreno, S.F., Santos-Filho. S., Rogers, P.A., Bernardo-Filho, M. and Guimarães, M.A. The effect of “Zusanli” (ST. 36) acupuncture on the bio-availability of so-dium pertechnetate in Wistar rats. Acupunct. Electrother. Res. 31: 33-44, 2006.

29. Senna-Fernandes, V., França, D.L., Santos, K.C., Sousa, R.S., Silva, D., Cortez, C.M., Bernardo-Filho, M. and Guimarães, M.A. Effect of Zusanli (ST.36) electroacupuncture at two frequencies on the bioavailability of (99m)Tc-sodium pertechnetate and on labeling of blood constituents in rats. J. Acupunct. Meridian Stud. 2: 135-146, 2009.

30. Senna-Fernandes, V., França, D.L.M.¸ Souza, D.E., Santos, K.C.M., Sousa, R.S., Manoel, C.V., Santos-Filho, S.D., Bernardo-Filho, M. and Guimarães, M.A. Acupuncture at ‘Zusanli’ (St.36) and ‘Sanyinjiao’ (SP.6) points on the gastrointestinal tract: A study of the bioavailability of 99mTc-sodium pertechnetate in rats. Evid. Based. Complement. Alternated. 2011: 823941, 2011.

31. Sethi, R.S., Mittal, B., Bhattacharya, A. and Singh B. Tc99m MDP bone SPECT in a case of osteomyelitis of the skull. Indian J. Nucl. Med. 25: 25-26, 2010.

32. Sharp, P.F., Gemmel, H.G. and Murray A.D. Practical nuclear medicine. London: Oxford University Press, 2005.

33. Souza, D.E., Rebello, B.M., Silva-Filho, R.C., Agostinho, R.T., Bastos, S.R.C. and Bernardo-Filho M. Nuclear medicine methods in the assessment of acupuncture effects: a short review. Braz. Arch. Biol. Techn. 50: 105-110, 2007.

34. Souza, D.E., Senna-Fernandes, V., Brito, L.C., Souza, R.S.S., França, D., Manoel, C.V., Almeida, M.C. and Bernardo-Filho, M. Acupunc- ture stimulation at Sanyinjiao: effect on the sodium pertechnetate bioavailability in rats. Am. J. Chin. Med. 35: 977-986, 2007.

35. Souza, D.E., Souza, R.S.S., Manoel, C.V., Pereira, M.O., Carmo, F.S., Fonseca, A. and Bernardo-Filho, M. Acupuncture stimulation at Taixi point: effect on technetium-99m methylenediphosphonate bioavailability in rats. Med. Acupunct. 23: 93-99, 2011.

36. Spencer, H.T., Sokol, L.O., Glotzbecker, M.P., Grant, F.D., d’Hemecourt, P.A., Micheli, L.J. and Trevesv, S.T. Detection of pars injury by SPECT in patients younger than age 10 with low back pain. J. Pediatr. Orthop. 33: 383-388, 2013.

37. Stockert, K., Schneider, B., Porenta, G., Rath, R., Nissel, H. and Eichler, I. Laser acupuncture and probiotics in school age children with asthma: a randomized, placebo-controlled pilot study of therapy guided by principles of Traditional Chinese Medicine. Pediatr. Allergy Immunol. 18: 160-166, 2007.

38. Stux, G. and Pomeranz, B. Basics of acupuncture. Berlin Heidelberg: Springer, 1998

39. Takahashi, T. Acupuncture for functional gastrointestinal disor-ders. J. Gastroenterol. 41: 408-417, 2006.

40. Yin, L., Jin, X., Qiao, W., Sun, J., Shi, X., Tian, J., Yin, D., Yao, S., Shao, M., Zeng, H., Shan, B., Tang, Y. and Zhu, K. PET imaging of brain function while puncturing the acupoint ST36. Chinese Med. J. 116: 1836-1839, 2003.

41. Zeredo, J.L., Sasaki, K.M. and Toda, K. High-intensity laser for acupuncture-like stimulation. Lasers Med. Sci. 22: 37-41, 2007.

42. Zhang, W.P. Effects of acupuncture on the pulmonary function and heart rate variability in different state of bronchial asthma. Zhen Ci. Yan Jiu. 32: 42-48, 2007.