Investigation of the Cellular Pharmacological Mechanism and Clinical Evidence of the Multi-Herbal Antiarrhythmic Chinese Medicine Xin Su Ning.

Xin Su Ning (XSN), a China patented and certified multi-herbal medicine, has been available in China since 2005 for treating cardiac ventricular arrhythmia including arrhythmia induced by ischemic heart diseases and viral myocarditis, without adverse reactions being reported. It is vitally important to discover pharmacologically how XSN as a multicomponent medicine exerts its clinical efficacy, and whether the therapeutic effect of XSN can be verified by standard clinical trial studies. In this paper we report our discoveries in a cellular electrophysiological study and in a three-armed, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Conventional electrophysiological techniques were used to study the cellular antiarrhythmic mechanism of XSN. Data was then modeled with computational simulation of human action potential (AP) of the cardiac ventricular myocytes. The clinical trial was conducted with a total of 861 eligible participants randomly assigned in a ratio of 2:2:1 to receive XSN, mexiletine, or the placebo for 4 weeks. The primary and secondary endpoint was the change of premature ventricular contraction (PVC) counts and PVC-related symptoms, respectively. This trial was registered in the Chinese Clinical Trial Register Center (ChiCTR-TRC-14004180). We found that XSN prolonged AP duration of the ventricular myocytes in a dose-dependent, reversible manner and blocked potassium channels. Patients in XSN group exhibited significant total effective responses in the reduction of PVCs compared to those in the placebo group (65.85% vs. 27.27%, P < 0.0001). No severe adverse effects attributable to XSN were observed. In conclusion, XSN is an effective multicomponent antiarrhythmic medicine to treat PVC without adverse effect in patients, which is convincingly supported by its class I & III pharmacological antiarrhythmic mechanism of blocking hERG potassium channels and hNaV1.5 sodium channel reported in our earlier publication and prolongs AP duration both in ventricular myocytes and with computational simulation of human AP presented in this report.

[Distribution laws of Chinese medical syndrome types and analyses of risk factors in senile hypertension patients: a clinical study].

OBJECTIVE: To explore the distribution laws of TCM syndrome types and to analyze the distribution of dynamic blood pressure curve, atherosclerosis, and age in senile hypertension patients. METHODS: Totally 1 131 senile hypertension patients were recruited from 7 provinces and municipal cities. Features of TCM syndromes, classification and distribution curves, and syndrome distribution laws were observed. The distribution curves of dynamic blood pressure, carotid atherosclerosis, and age were compared in each TCM syndrome types. RESULTS: There were four main syndrome types in 736 cases (56.15%), i.e., excessive accumulation of phlegm-dampness syndrome (210 cases, 16.02%), yin deficiency and hyperactivity of yang syndrome (177 cases, 13.50%), Gan-Shen yin deficiency syndrome (79 cases, 6.03%), and deficiency of qi and yin syndrome (252 cases, 19.22%). Besides, there were two more sub-types, i.e., collateral obstruction by blood stasis syndrome and collateral obstruction by phlegm and stasis. Circadian blood pressure monitor was completed in 211 cases. Of them, abnormal circadian blood pressure occurred in 152 cases (accounting for 72. 38%); yin deficiency and hyperactivity of yang syndrome, excessive accumulation of phlegm-dampness syndrome, deficiency of qi and yin syndrome plus collateral obstruction by blood stasis syndrome were most often seen. Color ultrasound of carotid artery was performed in 660 patients of main syndromes. The incidence was quite higher in those of excessive accumulation of phlegm-dampness syndrome (182 cases, 27. 58%), deficiency of qi and yin syndrome plus collateral obstruction by blood stasis syndrome or collateral obstruction by phlegm and stasis (322 cases, 48.79%). Yin deficiency and hyperactivity of yang syndrome was dominant in patients 60 -79 years old, while deficiency of qi and yin syndrome and Gan-Shen yin deficiency syndrome were dominant in patients older than 80 years. CONCLUSIONS: Excessive accumulation of phlegm-dampness syndrome, yin deficiency and hyperactivity of yang syndrome, Gan-Shen yin deficiency syndrome, and deficiency of qi and yin syndrome were main syndrome types in senile hypertension patients. There was statistical difference in the distribution curves of blood pressure, atherosclerosis, and age of various TCM syndrome types.

[Distribution characteristics of syndrome types in essential hypertension].

OBJECTIVE: To investigate the distribution characteristics of syndrome types of traditional Chinese medicine (TCM) in essential hypertension and to explore the distribution rule of TCM syndromes. METHODS: A multicenter, large-sample survey method of clinical epidemiology was applied to choose the patients with essential hypertension from North, Middle, and South China. A questionnaire was designed and filled in, then 477 untreated patients with first-diagnosed essential hypertension were selected and the information was recorded into FileMaker database. A cluster analysis method was utilized to study the TCM syndrome distribution rule of essential hypertension. RESULTS: Two-step cluster analysis was done from 3 to 7 clusters. Seven clusters were appropriate, which included deficiency of heart and kidney qi, hyperactivity of liver-yang, deficiency of yin and yang, stagnation of phlegm-dampness, phlegm-heat (subtype of stagnation of phlegm-dampness), blood stasis obstructing collaterals, and other syndromes. The symptoms presenting high percentage in each cluster were more significant in TCM theory. The syndromes of hyperactivity of liver-yang (24.1%) and stagnation of phlegm-dampness (27.1%) presented the high percentages, and deficiency of heart and kidney qi (10.1%), deficiency of yin and yang (8.4%), and blood stasis obstructing collaterals (9.0%) presented the low percentages. CONCLUSION: As compared with the current syndrome differentiation criteria, two-step cluster analysis results not only include the syndromes of deficiency of yin and yang, hyperactivity of liver-yang, stagnation of phlegm-dampness, but also cover qi deficiency and blood stasis.

[Potential of using pattern diagnosis of traditional Chinese medicine to improve the clinical use of antihypertensive agents].

Despite the availability of six classes of antihypertensive agents, control of blood pressure and improving patients' quality of life remain far from ideal. There is a wide variability in terms of the hypotensive effect and side effect profile for the same antihypertensive agent used in different patients. How to select the right agent to provide the most beneficial results in terms of efficacy and improvement of quality of life as well as to decrease clinical symptoms and minimize adverse reactions is an important therapeutic challenge. It has been suggested that clinical usage of pattern (Zheng) diagnosis of traditional Chinese medicine may improve the accuracy in selecting the right antihypertensive agents with improved efficacy and deceased adverse effects. Limited research in this area suggested the calcium channel blocker may work better in treating phlegmatic damp excess pattern and blood stasis pattern while beta-blockers may be more beneficial in the liver yang rising pattern. On the other hand, angiotensin converting enzyme inhibitors may be more suitable in a yin deficiency and yang hyperactivity pattern as well as combined liver and kidney yin deficiency pattern. More research studies using this innovative approach in improving the selection of antihypertensive agents including mechanistic studies are urgently needed.

[Exploration of TCM syndrome differentiation of coronary heart disease and coronary arteriography].

Coronary arteriography (CAG) examination is the widely accepted gold standard for diagnosis of coronary heart disease (CHD) nowadays. In order to explore the situation and value of CAG applied in TCM syndrome differentiation of CHD, and to facilitate the research on disease-syndrome diagnosis of CHD in integrated traditional Chinese and Western medicine (ICWM), the relationship between coronary arterial pathological changes and the TCM syndrome types was probed through reviewing literatures concerning the application of CAG in studying syndrome differentiation of CHD since 2000. The results showed that syndrome types are correlated to the severity and number affected of coronary artery branches. Along with the aggravation of CHD, TCM syndrome typing become even more complicated. There is a gap between the previous detectable index for CHD as well as the TCM syndrome typing and clinical practice. CAG is of vital importance in exploring rules of integrated syndrome differentiation and disease diagnosis of CHD. Therefore, to launch a nationwide multi-centric study on large sample of syndrome differentiation with ICWM is necessary, which should be based on the evidence-based medicine and by dint of the modern medical detecting technique to conduct the study comprehensively in combining differentiation of syndrome and disease, and in both macroscopic and microscopic views.

[Gaseous signaling molecule and study on activating blood circulation and removing stasis].

The finding of gaseous signaling molecule NO, CO and H2S, and the advocacy of "gas biology" concept have provided a novel thinking for the study of Huoxue Huayu (HXHY, a traditional Chinese medicine method of promoting blood circulation to remove blood stasis). The concept "Qi" in TCM and gaseous signaling molecule are correlated in respects of their source and mesomeric function. Study of HXHY could only be deepened through an overall cognition on blood stasis syndrome with the view of Qi-blood correlation.