Clinical And Animal Research On Acute Coronary Syndrome Treated By Wutou Chishizhi Tang

【Background】Acute Coronary Syndrome (ACS) covers the spectrum of clinical conditions ranging from unstable angina (shortened as UA) to non-ST-segment elevation myocardial infarction (shortened as NSTEMI) and ST-segment elevation myocardial infarction (shortened as STEMI) Present studies show that it is difficult to separate the three precisely because they have no clear boundary, and their basic pathology and path physiology are almost the same, which takes place due to the unstable coronary plaque rupture and then cause thrombosis, which will stop the blood supply to the heart or even sudden death.ACS is a disease with poor prognosis, its incidence has now increased year by year, which will do great harm to people's health, now it has become a focus in the research field of cardiovascular.The clinical manifestation of ACS is similar to a Traditional Chinese Medicine (shortened as TCM) disease named "chest pain" and "true heart pain. Zhang Zhongjing in his famous medical works " Synopsis of Prescriptions of Golden Cabinet" mentioned that "insufficiency of yang" maybe the most important pathogenic mechanism of it and used "Wutou Chishizhi Tang" to treat patients diagnosed as "purplish clots caused by insufficiency of yang syndrome"In recent years, evidence-based studies have shown that insufficiency of yang, cold coagulation may be the main TCM syndrome type of unstable angina, acute myocardial infarction. Small sample studies show that-Wutou Chishizhi Tang safe and effective treatment of unstable angina pectoris.【Objective】This thesis aims to lay the foundation for further research through the establishment of Integrated Traditional and Western treatment group and western medicine group, the comparison of their efficacies, the evaluation of ACS Wutou Chishizhi Tang on the clinical efficacy and safety, and the randomized, prospective animal study on its possible mechanism.[Methods] The author used a randomized, single blind methods in clinical research. From September,2008 to March,2010, the author collected 77 patients who met the diagnosis criterion of AMI and UA/NSTEMI from the First Affiliated hospital of Guangzhou TCM University and the second TCM hospital of Guangdong Province. We randomly divided them into the treatment group and the control group. Both groups used the modern standard western medicine, yet the treatment group used Wutou Chishizhi Tang, and the control group used a TCM placebo decoction (made of licorice, millet sprout, malt). Both groups took medicine twice a day and 200ml each time till the end of hospitalization. While in hospital, symptoms including physical feeling, adverse reactions after taking the drugs, cardiovascular events would be recorded. Vital signs, electrocardiogram, blood and urine and stool regular Test as well as liver and kidney function would be checked twice, the effect index such as blood coagulation, C-reactive Protein, interleukin-6, Fibrinogen would also be checked.In the preliminary animal experiment, the experimenter used different dose of vasopressin (Pit) in Animal experiments as to find out the most suitable dose by comparing the effect of myocardial ischemia time, heart rate through ECG monitoring as well as all adverse events. In the randomized controlled trials, after myocardial ischemia animal models were produced, the experimenter would give Wutou Chishizhi Tang through the duodenum puncture, and would check the serum troponin (cTNI), hydroxyl radical, superoxide dismutase (SOD) levels changes in order to assess the possible pathways.[Results] The statistics shows that TCM symptom scores have a good correlation with that of severity of ACS, i.e. patients who have higher symptom scores are in a more serious condition. In terms of healing effect, in the treatment group, there are 22 cases of remarkable change on angina symptoms 14 effective cases,4 noneffective cases, and the total efficiency rate is 90%. In comparison, in the control group, there are 16 cases of remarkable change,19 effective cases and 2 noneffective cases, and the total efficiency rate is 94.59%, and there is no significant difference. In terms of the improvement of TCM symptom, statistics in the treatment group is 27.38%, and 15.16% in the control group. The difference is of statistically significant, especially for the qi-deficiency of heart, yang deficiency symptoms (P<0.05). And for blood stasis, phlegm obstruction, both group shows no significant difference though there is a trend of better improvement in the treatment group than in the control group, and no patient in both groups got worse. Laboratory indicators shows no significant difference between two groups(P> 0.05). When Comparing the adverse events, the author found four patients in two groups had experienced vomiting after taking TCM decoction, mostly were caused bt acute myocardial infarction. There are only only two people in the treatment group who cannot tolerate Wutou Chishizhi Tang, There are no significant difference in terms of thirsty, headache or other adverse events rate between the two groups. Patients of both groups had not experienced angina, arrhythmia, new heart failure, sudden cardiac death, and so on during hospitalization observation. The treatment group were treated with surgery or PCI after thrombolysis did not affect the clotting time.Animal experiments suggest that the administration of vasopressin via vein is better than intraperitoneal injection, and intravenous injection may be an ideal modeling approach. Effect of myocardial ischemia, stability is positively correlated with dose, however, the greater dose we used, the more possibility of causing adverse events as malignant arrhythmias, hematuria, sudden death myocardial injury and so on. Vasopressin could not change myocardial infarctionAnimals randomized controlled trial suggested that the treatment group improved a little better than the control group by ECG assessment, which recover the ST segment depression. laboratory indicators such as SOD, hydroxyl radical show no significant improvement after treatment. During the experiment no rats had the manifestations of heart-beating rate rising, ventricular tachycardia, sudden death and other adverse events.[Conclusion] 1. There is a high correlation between symptom scores and disease scale in that the higher the scores, the more serious a patient will be. And patients with yang deficiency are usually with the symptom of phlegm obstruction, blood stasis, which is in accordance with the TCM theory "Weak pulse at yang and wiry pulse at yin ". The table can be used not only to evaluate patients with ACS disease, but also to describe and evaluate the efficacy of TCM in a more comprehensive and objective manner. Therefore, it can reflect the comprehensiveness and objectivity of TCM by comparison to that of the change of chest pain, the amount of nitroglycerin, ECG.2, Wutou Chishizhi Tang is safe and effective for ACS patients. Patients treated with TCM improve better than that in the control group, especially for "yang deficiency" and "heart qi deficiency" type.No patient got worse after treatment3. Animals experiments suggest a mild and non-significant effect of acute Wutou Chishi Zhi Tang on myocardial ischemia, and no improvement for the SOD, and other indicators of hydroxyl radical. So the author considers the possible mechanism may be the expansion of coronary spasm, but further studies would be needed in the future so as to find out the mechanism. During the experiment, rats show no arrhythmia, hematuria and so on, and no increasing trend of cTNI, which suggests that the drug is safe.4,This study used intravenous infusion of vasopressin in ischemic modeling, which have shown better effect than previously method used, but some rats came to hematuria due to larger dose of pituitary. The reason we think is that high-dose vasopressin may act not only on coronary but also on other vital artery such as the renal artery, mesenteric artery, the carotid artery and so on, so many important organs will be damaged during the injection, which may difficultly evaluate drug efficacy. I personally believe that vasopressin may not be the best medicine for making drug-producing- myocardial- ischemia model.5. The present research shows that Wutou Chishizhi Tang does not have the advantage in the improvement of chest pain in comparison to western medicine, but does have the advantage in overall syndromes. So while in acute period of ACS, useing TCM drugs may not improve the ischemic symptoms, but may have an improvement in terms of overall syndromes. The reasons that symptom scores improved in the standards have not yet reached the estimated standard may be due to the insufficient time for observation. Thus for the future TCM-related intervention researches, we should focus no more on myocardial ischemia change in the acute phase, but should extend the observation time, through which we may finally reflect the real value and assessment for TCM drugs used in CAD. Furthermore, describing TCM effect by means of life quality description maybe more appropriate, and thus can embody the remedial values of TCM.