Protective Effects And Mechanisms Of Total Saponins Of Paeonia On Acute Myocardial Ischemia In Dogs

In modern society, myocardial ischemia disease has become common disease and frequently occurring illness threatening human health and life. The incidence rises day by day. Therefore, the study for the mechanism of myocardial ischemia disease and the search the drugs used to treat myocardial ischemia are important topic at present.Paeonia is the root of Paeonia Lactiflora Pall. Total Saponins of paeonia (TSP) is main active site in Paeonia. It was reported that TSP has the effects of anticoagulated blood, anti-thrombus, anti-artherosclerosis, protecting heart and liver, anti-tumor effects, and can protect from injury induced by cerebral ischemia.We investigated the protective effects of TSP on the area and degree of myocardial infarct, electrophysiology, myocardial enzymology, quantitation histology and hemodynamics by ligation of left anterior descending artery in the anesthetized open chest canines. We investigated protective effects and mechanisms of TSP. Thirty canines were randomly divided into 5 groups (6 canines in each group), they are control group, compound danshen 2mg·kg-1group, TSP 1.5mg·kg-1, 3mg·kg-1, 6mg·kg-1 group. All drugs were administrated by intravenous drop infusion.Canines were anesthetized with pentobarbital sodium 0.03g·kg-1 administrated intravenously. The acute myocardial ischemia model was made in open chest canines. Then trachea was cannulated for artificial respiration. The right common carotid artery cannula was made to monitor the blood pressure. The femoral vein was catheterized for drugs administration and obtain blood sample. The left ventricle cannula was operated to measure left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),maximum left ventricular rise rate and maximum left ventricular fall rate(±dp/dtmax). The chest was opened by a leftthoracotomy, followed by sectioning the fourth bibs. The pericardium was opened and heart was suspended in a pericardial cradle. A segment of left anterior descending (LAD) coronary artery was isolated. Coronary blood flow (CBF) and cardiac output (CO) were measured continuously by the MFV-3200 electromagnetic flow meter probe. ECG of standardⅡ,epicardium electrocardiogram(EECG)and heart rate were recorded at the same time. Hemodynamic evaluations were performed before TSP administration and at 3,5,10,20,30,45,60,90,120,150,180,210,240min after the TSP administration. Arterial and venous oxygen content were determined before TSP administration and at 10,15,30,60,90,120,240 min after the TSP administration. Heart was exposed and left anterior descending coronary artery was ligated to lead acute myocardial ischemia in canines. Myocardial ischemia scope (N-ST) and myocardial ischemia extent (∑-ST) were determined by the epicardium electrocardiogram (EECG). We can calculate stroke volume(SV),cardiac index(CI), stroke index(SI), myocardial blood flow(MBF),coronary vascular resistance (CVR) and total peripheral resistance (TPR) by the above hemodynamics data. Blood was sampled at 360 min after the TSP administration. Serum was separated from blood cell, then lactate dehydrogenase (LDH), aminotransferase(AST),creatine kinase(CK), superoxide dismutase( SOD),free fatty acids(FFA), lipid peroxidation (LPO), glutathione peroxidase (GSH-Px) were determined at the end of each experiment.The heart was removed and cut into coronal sections and immersed in N-BT solution at 37°C. The percentage ratio of the weight of infracted necrotic myocardium to that of total ischemic myocardium was calculated and designated as the infarct size (%). The heart was examined by transmission electron microscope.Results showed that TSP can reduce the degree of myocardial ischemia anddecrease myocardial infarction square. It also can decrease the activity of LDH, CK and AST. TSP can improve SOD and GSH-Px activity, but reduce LPO and FFA content in serum in acute myocardial infarction canines. Pathology examination showed that TSP can ameliorate the changes induced by ischemia in myocardial ultrastructure markedly. The results suggest that TSP has the protective effect on myocardial cell from injury induced by ischemia and anoxemia.TSP can decrease myocardial oxygen uptake, total peripheral resistance,coronary artery resistance, resist the decreasing of myocardial blood flow,cardiac index (CI), stroke index (SI), cardiac output(SD),cardiac output (CO),and relieve myocardial infarction. All the results indicate that TSP can ameliorate the changes of hemodynamics in myocardial infarction canines. Those mentioned above can result in decrease of myocardial oxygen uptake and cardiac oxygen consumption. Moreover, TSP can improve myocardial blood supply, ameliorate cardiac metabolism and balance the relation between supply and demand.In conclusion , the present study demonstrates that TSP has the protective effect on acute myocardial infarction. Its mechanisms probably include improving hemodynamics, balancing the relationship of ischemia and oxygen supply, decreasing cardiac oxygen consumption, increasing myocardial blood flow and ameliorating cardiac metabolism, etc. TSP may be an effective drug for prevention and treat of myocardial ischemia ischemia.