Screening And Anti-myocardial Ischemia Pharmacodynamics Research Of The Salvianolic Acids Compound Injection

SP is a kind of anti-myocardial ischemia compound injection which was made of active fractions of Salvianolic acids（S）and Panax quinquefolium 20s-protopanaxdiol saponins（P）. The purpose of this paper is to search for the effective doses of active fractions of S and P by myocardial ischemia rats induced by Pituitrin（Pit）and on the basis of this, to screen compounds to get optimum ratio of S and P with three doses by two factor and three level orthogonal experiment. Additionally, the anti-myocardial ischemia effects and the mechanism of this medicine were preliminarily studied.The results indicated that S and P can oppose T wave elevation in acute myocardial ischemia rats induced by Pit after 10 seconds obviously in a concentration of 10,30,50 mg/kg and 25,50,100 mg/kg. Through two factor and three level orthogonal experiment, the optimum ratio of effective fractions of the two Chinese traditional medicines is determined as 2:1. The results of pharmacodynamics on this ratio showed that SP prolonged the survival time of normal mice and acute myocardial ischemia mice induced by Isoprenaline（Iso） in normobaric hypoxia. Meanwhile, it opposed T wave elevation and ST segment drift on electrocardiogram in acute myocardial ischemia rats induced by Pituitrin（Pit） and Isoprenaline（Iso）. It also increased the activity of SOD,decreased the content of MDA in the blood serum of acute myocardial ischemia rats, and diminished the release of lactic dehydrogenase（LDH）and creatine phosphokinase（CK）significantly in coronary ligated rats with acute myocardial infarction. The results above indicated that SP had the protective effects on ischemia myocardium. In hemodynamics studies of dogs with ligation of coronary artery, SP produced significant increment of coronary blood flow（CBF）, cardiac output（CO）, left ventricular systolic pressure（LVSP）and ventricular pressure maximal change rate(±dp/dt_max), while the increment of left ventricular end diastolic pressure（LVEDP）after coronary ligation in dogs was prevented by the SP administration. In addition, total peripheral vascular resistance（TPVR）and coronary vascular resistance（CVR）were decreased. As a result of these actions, myocardial oxygen consumption in ischemia condition is reduced.In conclusion, the results presented in the paper demonstrated that SP has strong anti-myocardial ischemia effects, and better than simple recipe. The mechanism is related to ameliorating hemodynamical indexes, increasing the SOD activity, stabilizing myocardial cell membrane, decreasing the leakage of myocardium enzyme, regulating the balance of PGI₂/TXA₂、anti-platelet aggregation effects and ameliorating hemorheology. This study provided the experimental basis to the clinical application of SP. However, the mechanisms accounted for the effects of SP’s anti-myocardial ischemia deserve further study.