| Myocardial ischemia has been arousing the global attention due to its high incidence and mortality rates in recent years, which severely threaten human's health and life quality. Numerous experiments have been done to probe into the mechanisms of the pathophysiology of myocardial ischemia. However, the specific mechanisms are still unclear up to now due to its extreme complexity. Thus, it is necessary now to investigate the occurrance and development mechanism of myocardial ischemia and look for the right targeted drugs with good therapeutic effect and less side effect. Drug therapy is still the major treatment in clinical practice for ischemia. Xinbikang Capsule is a Chinese drug compound with the composition of traditional Chinese medicine Danshen, Sanqi etc, which have been proved to have preventive effects on the myocardial ischemia.Objective:In this project, we aim to find the interventional role of Xinbikang Capsule on the acute myocardial ischemia canine model built by ligating the left anterior descending of coronary artery. The cardio-protective effects of Xinbikang capsule has been investigated by observation of myocardial infarct size, ischemia degree and ischemic area, serum content of myocardial enzymes LDH, CK, AST. To further elucidate the interventional mechanism of Xinbikang capsule on the acute myocardial ischemia, we determined the cardiac function parameters and hemodynamics changes.Methods:40 healthy adult canines are used to divided randomly into five groups (eight canines in each group), they are groups control, DAXXK 50.0 mg·kg-1, Xinbikang 16.8 mg·kg-1, Xinbikang 33.6 mg·kg-1 and Xinbikang 67.2 mg·kg-1. The acute myocardial ischemia model was made by ligating the left anterior descending of coronary artery in canines. The drug was administered by duodemun injection before ligation. Myocardial infarct size was measured 6h after ischemia using NBT staining. Heart rate (HR), left ventricular pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal rate of left ventricular pressure (+ dp / dtmax), coronary blood flow (CBF) and cardiac output (CO) were recorded. Blood samples of before administration and 60,90,150,180,240min after administration were analyzed to calculate blood oxygen content. Parameters like coronary resistance (CVR), cardiac index (SI), cardiac index (CI), myocardial blood flow (MBF), total peripheral resistance (TPR), left ventricular work index (LVWI), stroke volume (SV), myocardial oxygen uptake (COU) were also calculated. The epicardium electrocardiogram was measured by polygraphy to determined myocardial ischemia degree (Σ-ST) and myocardial ischemic area (N-ST).Results:In comparison with control group, Xinbikang groups can reduce the myocardial infarct size and diminished the ischemia degree and area. Meanwhile, the myocardial enzymes contents in the serum have ascended after Xinbikang capsule administration. HE dye demonstrated that the Xinbikang greatly ameliorated the injury extent induced by ischemia. Moreover, Xinbikang can improve the cardiac function and hemodynamics by increasing the cardiac output, Stroke volume, cardiac index and stroke index. On the other hand, the total peripheral resistance and coronary artery resistance as well as the left wall work index were decreased. To regulate the oxygen metabolism in the ischemia heart tissue, Xinbikang capsule can enhance the myocardial blood flow, whereas decrease the myocardial oxygen uptake to balance the oxygen supply and consumption.Conclusion:Xinbikang Capsule has played an interventional role in myocardial ischemia injury by reducing myocardial infarct size, ischemia degree and area. The ascending serum enzyme levels reveal that Xinbikang capsule can maintain the integrity of myocardial cell membrane and reduce enzyme leakage. The interventional mechanism refers to making a new balance between oxygen supply and consumption together with enhancing the heart work efficiency.In conclusion, Xinbikang capsule does have interventional effects on acute myocardial ischemia and the mechanism have been elucidated. This project made a pharmacological preparation for the future clinical applications of this capsule. |
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