Experimental And Clinic Studies On Curative Effect Of Chronic Heart Failure And Prevent Digitalis Toxicity By Huangqi Injection

BackgroundCongestive Heart Failure(CHF) is a complex clinic syndrome that can resultfrom all kinds of heart diseases in their last serious stage. The hospitalization rate of CHF in patients with cardiovascular disease is approximately 20%, and the mortality is 40%. Patients with CHF is poor prognosis, the five years survival rate is like tumor. So the management of CHF is the importantObjectiveTo study the improvement effect of Huangqi Injection on the haemodynamic parameters in CHF rats, symptom of patients with CHF, and the prevention of the occurrence of digitalis toxicity. We also to primary study the mechanism of its decrease the prevalence of digitalis toxicity. We can provide some theories and clinic groundwork for using the Huangqi Injection to treat CHF and to prevent the occurrence of digitalis toxicity.Content and MethodsThe Digitalis is the basal drug to treat CHF. The major problem of the use of digitalis is the toxicity. The mechanism of the digitalis toxicity is that can restrain the activity of Na~+-K~+-ATP ase in myocardium. HuangqiInjection which can anti-arrhythmias in patients with CHF is also the commonly use drug to treat CHF. The mechanism of anti- arrhythmias is considered that Huangqi Injection can resume the activity of Na+-K+-ATP ase. We have observed that Huangqi Injection can protect the guinea pig myocardium from the Ouabain(a kind of digitalis) toxicity in former experiment. It indicates that Huangqi Injection can decrease the prevalence of digitalis toxicity.1. Experimental research60 SD rats those were successfully established CHF animal models with abdominal aortic banding for 8 weeks were randomly divided into six groups. The A, B, and C group, which is respectively normal saline group, lower dosage Huangqi Injection group and high dosage Huangqi Injection group, will do the acute toxicity experiment. The E, F and G group, which is respectively normal saline group, lower dosage Huangqi Injection group and high dosage Huangqi Injection group, add 10 normal rats as D group, will do the chronic toxicity experiment. The rats in A, B and C group were anaesthetized and then 3# extradural anaesthesia tube which wes insert the left venticle through the right common carotid was connect the 8 lead physiologyical recorder with the pressure transducer. We insert the venous cannulate through the left jugular vein and respectively inject the drug(5ml) which used in A, B and C group, and then inject 0. 005% Ouabain Injection with 12. 5mg/min by electronic constant injector. Monitoring the ECG in oscillograph and recording the dosage of Ouabain when ECG shows Ventricular Tachycardia(VT), Ventricular Flutter(VF). We also record the haemodynamic parameters, such as Heart Rates(HR), Left Ventricular Systolic Pressure(LVSP), Left Ventricular End Diastolic Pressure(LVEDP) and Left Ventricular Pressure change rate(± dp/dtmax) in such four time point, before injection (point I), 1 min after injection of normal saline or Huangqi Injection (point II), lmin after injection of Ouabain Injection (point III) and the ECG show VT (point IV).At last killed rats and tested the activity of Na+-K+-ATP ase in myocardium cell membrane.As for the chronic toxicity groups, rats in D group were feed normal saline as well as rats in E, F and G group were feed with digoxin solution 0. 125mg/kg ? d. At the same time, the rats in four groups were injected in abdominal cavity respectively for normal saline 2ml/d, normal saline 2ml/d, Huangqi Injection 2ml/d and Huangqi Injection 4ml/d. A week later, we monitored and record haemodynamic parameters of rats , killed them and tested the activity of Na+ —K+—ATPase in myocardium cell membrane.2. Clinic researchWe made a retrospective investigation of medical history of the in-patients with CHF who hospitalized in Cardiovasology yard of First Affiliated Hospital of Guangzhou University of Traditional Chinese and First Affiliated Hospital of Sun Yat-sen university and were treated with digitalis. The patients were divided into two groups according whether they were used or not used Huangqi Injection. To study the effect of cardiac function treat by Huangqi Injection combine with digoxin, and prevention of the occurrence of digitalis toxicity.Results1. Experimental researchThe LVSP and +dp/dtmai were principal haemodynamic parameters those can reflect the systolic function of heart. We observed in our experiment that LVSP and +dp/dtBM of rats in A, B and C group have non-significant difference in statistics (P>0. 05) after the rats were successfully established CHF animal models. The parameters also have non-significant difference in point II, and rise significantly in point III. When it was in point IV, the parameters became lower significantly(P<0. 01) than those were in early three points. There were extremely significant difference(P<0.01) between A and B group, andsignificant difference between B and C group(P<0.05).The LVEDP and —dp/dt?, were principal haemodynamic parameters those can reflect the diastolic function of heart. Those parameters in those three group have non-significant difference in statistics (P>0.05) in point I. LVEDP in point II became higher obviously than those in point, But there were non-significant difference among three groups(P<0. 01). -dp/dt?, in point II also has no significant difference with this in point I(P>0. 05). In point III, the parameters have non-significantly difference. When it was in point IV, LVEDP became higher significantly(P<0.01), -dp/dtMI became lower significantly(P<0.01) than those were in early three points. There was extremely significant difference(P<0.01) between A and B group, and significant difference between B and C group(P<0. 05).The tolerance doses of Ouabain in B group rats is bigger than those in A group lower than those in C group(P<0.05).The activity of Na+—K+ATP ase in myocardium membrane in rats of the three groups decreased extremely, there were extremely significant difference between there three groups and D groups (P<0.01). It suggested that Ouabain seriously restrain the activity of Na+—K+ATP ase. And it was the reason that leads to Ventricle Premature Contraction(VPC), VT, even VF of rats.In chronic digitalis toxicity experiment, we have observed that the Heart Rate of rats in E, F and G group decreased significant than D group. The parameters of rats in E, F, G group, not only those reflect the systolic function, but also the diastolic function, were significant different from those of D group rats (P<0.05). The ECG shows that, rats in E group have more VPC than D group. LVEDP is more higher than that of A, B and C group(P<0. 01), while LVSP^ ±dp/dtmaxdecreased obviously (P<0. 05). That demonstrated that the rats were posined by digoxin. The cardiac systolic and diastolic functions were worse than those of rats with CHF. Compared with those of E group, LVSP and idp/dtw, of F group increased, LVEDP decreased, VPC decreased obviously.