The Protective Effect And Mechanism Of New Shenfu Injection On Congestive Heart Failure In Rats

Congestive Heart Failure is a kind of disease which is caused by the reduction of the heart's systolic ejection function and/or the diastolic filling function, in the condition of normal blood volume or a slight increase in blood volume, although after a variety of compensation, still cardiac output can't supply the metabolic needs of the organism, thereby caused a kind of clinical syndrome which is characterized by organ blood supply insufficiency and engorgement of pulmonary veins and systemic venous.Ancient prescription, shen fu decoction has the power of warming yang and benefiting qi. SFI is a kind of Chinese material medica preparation which is based on shen fu decoction , it is normally used to cure congestive heart failure. Clinically proven , SFI could increase the CHF patient's cardiac output,cardiac index and ejection fraction, increase left atrial early diastolic peak(E)decrease left atrial early systolic peak(A), which makes the ratio E/A increased.Modern pharmacological studies also have shown that SFI can enhance myocardial contractile force,enhance cardiac ourput,,increase renal blood flow, so as to promote urination,reduce cardiac stress, and improve cardiac function. The active ingredient of ShenFu decoction has many effect. For example the ginsenoside has the effect of expending coronary artery, reducing myocardial oxygen consumption, improving heart function, but also blocking the cardiac cell membrane calcium channels, reducing intracellular calcium load, promoting cardiac cells to repair, removing free radicals, reducing hypoxia on myocardial injury. Demethylcoclaurine can significantly improve myocardial pulsating frequency and amplitude,increase cardiac contractility.But the ingredient of the SFI is still not clear, its quality is unpredictable. So we use those kown chemical compositions of ginseng and aconite to mix by some ratio, and the GP and AP , then we get three kinds of injections. We expect to develop a new drug which solved the problem of the unpredictable quality.After ligating the left anterior descending coronary artery caused rats acute myocardial infarction model, six weeks later, SFI and NSFI were given to treat and after two weeks HE staining of myocardial cells for cardiac morphology; observe the hemodynamics by intubating rats'common carotid artery; took blood serum to determine the content of SOD, MDA, GSH-Px,TNF-α,IL-6, and ALD.Acute myocardial infarct model was established as follows: after anesthetised with ether, rats were face upward fixed on the operating table. The chest was opened between the left third and fourth rib and the heart was exposed. Find the left anterior descending coronary artery and a nylon suture attached to a fine needle was placed under the left anterior descending coronary artery and ligated coronary artery immediately. After the heart was return into the chest, the blood and water in the chest were squeezed out and close the chest swiftly. The time opening the chest is no more than 30 seconds. Sham surgical group placed the suture only but not ligate coronary artery. Every group of rats was injected penicillin 7d after operation. After 24 hours of ligating coronary artery, rats were anesthetized by 10% chloral hydrate(30mg/kg, ip), recordedⅡECG trace to observe the changes of ST segment and T wave. After given drugs treat , we observed the hemodynamics by intubating rats'common carotid artery by RM-6000 Multi-channel physiological recorder: LVSP,±dp/dtmax,LVEDP ,HR and determined the content of SOD, MDA, GSH-Px, TNF-α,IL-6 and ALD.The result shows as follows: NSFI can decrease HR and LVEDP, increase SBP,DBP,MAP,LVSP and±dp/dtmax in HF rats. Besides that NSFI can reduce content of MDA, TNF-α, IL-6,ALD and increase activity of SOD,GSH-Px, and NSFI improve myocardial morphology as well. The GP and AP, which are components of NSFI can be significantly increase MAP, LVSP and + dp/dtmax in HF rats, but the GP's influnce to HR and to -dp/dtmax had no significant effect; the AP can significantly reduce HR in HF rats, but it had no significant effect to decrease LVEDP, which is indicating that the role to the heart of NSFI may be the result of GP and AP's synergy effect; GP can increase activity of SOD and GSH-Px, AP only reduced content of MDA, and has no significant effect to SOD and GSH-Px, suggesting that its anti-oxidative damage increased SOD and GSH-Px activity may be the role of the GP concerned; NSFI, SFI can significantly reduce the ALD content, but the GP and AP is not statistically significant, suggesting that their effects to reduce cytokine release and the role of the RAAS system, possibly are the results of GP and AP's synergies.So we can conclude that: the NSFI has the positive effect of protecting cardiac muscle. This kind of function is probably the synergy results of ginseng and aconite which are the major raw material of the NSFI.