Protection Of Exogenous Creatine Phosphate On The Heart Of Rat Under Hypoxia

Background:It was detected that chronic hypoxia can cause heart failure, pulmonary hypertention and other abnormalities of cardiovascular system.At present,the main treatment of these diseases that are caused by hypoxia is oxygen therapy,but the therapeutic effect is not satisfied.Exogenous creatine phosphate was reported that it can increase the supplementary of cardiac energy and improve the cardiac function.But the mechanisms of it was not totally identified.We suggested that CP can prevent and improve the cardiac function of rats that under the condition of hypoxia.Objective:The aim of this study is to determine the possibility and safety of exogenous CP to protect the function of rat's cardiovascular system.Methods:50 male wistar rats were randamized into 5 groups:normal control group,hypoxia control group,CP+hypoxia group,hypoxia+oxygen therapy group,CP+hypoxia+oxygen therapy group.The rats except normal control group were put into the hypoxic compartment in which the oxygen concentration was maintained around the level of 10±0.5%for a week.After a week,the rats were killed,body weight,heart weight,hemodynamic index, cardiac enzymes were measured.The changes of ATP,ADP,AMP of cardium were also observed.We also observed the histology of the lungs and the peripheral pulmonary arteries,and the ultrastructure of the myocardium.Results:1.Hemodynamic measurement:The therapeutic alliance of CP and oxygen therapy could degrade the blood pressure obviously.And the cardiac function could be improved obviously too.The therapeutic alliance was better than single therapy.2.Cardiac enzymes:CK,CK-MB and LDH:It was obviously higher in the other 4 groups than in control group(P＜0.05).It was obviously lower in CP+hypoxia group than in hypoxia control group(P＜0.05).It was obviously lower in hypoxia+oxygen therapy group than in hypoxia control group and CP+hypoxia group(P＜0.05).It was obviously lower in CP+hypoxia+oxygen therapy group than in the 3 groups above(P＜0.05).3.Content of myocardium ATP:It was obviously lower in the other 4 groups than in control group(P＜0.05).It was obviously higher in CP+hypoxia group than in hypoxia control group(P＜0.05).It was obviously higher in hypoxia+oxygen therapy group than in hypoxia control group and CP+ hypoxia group(P＜0.05).It was obviously higher in CP+hypoxia+oxygen therapy group than in the 3 groups above(P＜0.05).4.Histology of lungs and peripheral pulmonary arteries:Histology photomicrographs showed the pulmonary alveolus in the normal control group were clear and integrity.In the other 4 groups,the walls of pulmonary alveolus were obviously thickened,and the structures were irregular and integrity.The walls of peripheral pulmonary arteries were thickened.5.Ultrastructure of myocardium:Electron micrographs showed the structure of mitochondria was normal in normal control group.The mitochondria in hypoxia control group and hypoxia+oxygen therapy group were swelling,and the mitochondrial cristas were irregular,ruptured,and disappeared.The mitochondria in hypoxia+creatine phosphate group and hypoxia+creatine phosphate+oxygen therapy group were integrity,and the mitochondrial cristas were regular.Conclusion:Exogenous creatine phosphate is effective on improving myocardial energy metabolism and protecting against myocardial structural injury in hypoxic rats.And it can improve the cardiac function,relieve the lung edema.The mechanism may be the protection of the membrane and improving myocardial energy metabolism.