The Protective Effect And Mechanism Of Ramipril On Myocardial Infarction In Dogs

Coronary atherosclerotic heart disease is a kind of disease which is caused by blood vessel stenosis or occlusion cavity due to coronary atherosclerosis or (and) by myocardial ischemia,hypoxia or necrosis due to coronary artery functional changes(cramps).Angina are a group of clinical syndromes which are caused by temporary myocardial ischemia,hypoxia and whose main performance is paroxysmal chest pain.In the modern society,alongside the changes of the influencing factors such as lifestyle,cardiovascular and cerebrovascular diseases have ranked among the major diseases that threaten people's life,health and quality of life.Moreover,the disease is becoming more and more harmful because of the gradually increasing incidence,especially the cardiovascular disease in China with the highest incidence rate among all diseases.Angina pectoris is one of the diseases.Along with the improvement of people's standard of living and the development of the aging of the population in China,its incidence and mortality rates are showing an upward trend year after year,and it has become the number one killer that endangers the life and health of our people. Although drug treatments keep emerging,results of the prevention of coronary heart disease are still far from satisfactory.Nowadays the pharmaceutical market is in urgent need of new drugs for the treatment of coronary heart disease with high efficiency and low toxicity.In our country,with the improved stands of our life and the extension of population average life span,the rate of ischemic heart disease has increased year by year.It has become one of de main disease which hurts human healthy in the whole world.Thus,to search safe and effective drugs used for preventing from and curing of ischemic heart disease is an important task of medicine research.Ramipril belong to angiotensin-converting enzyme inhibitor(ACEI).Altho the therapeutic action of ACEI and ABR on acute myocardial infarction has been approved in clinic,whose clinical curative effect is better are constantly debated.Especially,that combination application of ACEI and ABR can or cannot create synergistic effect in treatment of acute myocardial infarction not yet was reported up to now.The text was practiced used the acute myocardial infarct (AMI) model of ligated left anterior descending coronary artery(LAD).MIS was calculated and the activities of serum creatine phosphokinase(CK),lactate Dehydro- genase(LDH),aspartate aminotransferase(AST),superoxide dismutase (SOD) and glutathione peroxidase(GSH-Px),the contents of serum malondialdehyde(MDA) and free fatty acid(FFA),and the levels of plasma endothelin(ET),angiotensinâ…¡(Angâ…¡),prostacycline(PGI₂) and thromboxane A₂(TXA₂) were determined.Blood was collected to determine low shearing specific viscosity,middle shearing specific viscosity,high shearing specific viscosity and plasma specific viscosity.The protevtive effect of Ramipril on experimental myocardial infarction in dogs and its mechanism analysis were reported in this paper.Acute myocardial infarct(AMI) model was established as follows:after anesthetized by 3%barbital sodium(30mg/kg,ip),dogs were face upward fixed on the operating table.The neck was cut open and put the trachea tube in it in order to make the dogs breath like normal.Make the dogs down on right and open the chest from the left fourth rib,the heart was exposed.Find the left anterior descending coronary artery and a nylon suture was placed under the left anterior descending coronary artery.Sham surgical group placed the suture only but not ligate coronary artery.The activities of serum creatine phosphokinase(CK),Aspartate aminotransferase(AST) and lactate ehydrogense (LDH) were tested with COBAS-FARA automatic biochemical analyser. Activities of serum SOD and GSH-Px,content of MDA.Slice ischemic myocardium and weigh.Take them out after dying completely.Normal tissues were dyed while ischemic tissues not.Slice ischemic myocardium and weigh. Activities of serum CK,LDH,AST,SOD and GSH-Px,content of MDA,and levels of plasma ET,Angâ…¡,PGI2,TXA2 and FFA content of infarct and noninfarct area were determined.Blood was collected to determine low shearing specific viscosity,middle shearing specific viscosity,high shearing specific viscosity,and plasma specific viscosity.Activities of serum SOD and GSH-Px, content of MDA.Slice ischemic myocardium and weigh.Cut off atrium tissue and fat,crosscut myocardium of left ventricle into four or five slices,take them out after dying completely.Normal tissues were dyed while ischemic tissues not. Slice ischemic myocardium and weigh,.MIS was expressed as the ratio of ischemic myocardium weight to left ventricle wet weight.The results showed that:in dogs treated by Ramipril(in a dosage of 0.5, 1 and 2mg/kg),the MIS was significantly reduced,the activities of serum CK, AST and LDH,the levels of plasma ET,Angâ…¡and TXA₂ and the content of serum FFA declined,while the level of plasma PGI₂ and ratio of PGI₂/TXA₂ were increased signficatly.In addition,the content of serum MDA and viscosity of blood and plasma were declined,activities of SOD and GSH-Px were increased markedly.What we observed suggest that Ramipril has protective effect on myocardial ischemia by improving free radicals and myocardial metabolism etc.At present,it is considered that the mechanism of preventing from myocardial ischemia is to decrease the oxygen-consumption of myocardium,to increase blood-supply of myocardial ischemia,to improve myocardial FFA metabolism,to prevent myocardial cell from damage of peroxidation and to decrease the blood viscosity of myocardial ischemia etc.Ramipril has displayed better pharmacological activities about several aspects as stated before which hits that Ramipril prevents ischemial myocardia through many paths.Ramipril,in our view,may be an effective drug for prevention and cure of myocardial ischemia.