The Protection Of Phosphocreatine On The Function Of Rat Of Myocardial Hypertrophy And Heart Failure

The mechanism of heart failure involves many factors, such as the abnormality of exciting-systole coupling , calcium metablism disorder, increasing of oxidative stress and cell apoptosis. They all related to energy metablism disorder of cardiomyocyte in the end. Mitochondrial is the key site of energy production. It is confirmed to be very important in the mechanism of ischemic heart disease and heart failure. Recent study show that mitochondrial is also the regulator of cell apoptosis.Creatine phosphate ( CP) is an naturally occuring high energy phosphate. It is reported to be effective against myocardial ischemia and can improve heart function .But it's mechanism is still not very clear, and its effect on the function of mitochondrial is still needed exploring .First?we used ARVC(adult rat ventricular cardiomyocyte) to observe the protection role of CP on mitochondrial function in the condition of oxidative stress. Single cell was isolated as Melvin R.has described. Flowcytometry combined with fluorescent dyes was used to measure the changes of mitochondrial membrane potential( A y m), ROS production and apoptosis. H2O2 was used to induce oxidative stress, its effective concentration is 0.2mmol/L. CP( lOmmol/L) was given lOminutes before H2O2 does.The results show that CP can effectively prevent the decrease of mitochondrial membrane potential, preserve the cardiomyocyte of oxidative injury and reduce apoptosis.We also used the model of pressure-overload hypertrophy rat to observe the long term treatment effect of CP. Through subtotal abdominal aortic banding, we successfully make the model of compensated left ventricular hypertrophy and heart failure.Fourty-five rats with left ventricular hypertrophy(LVH) secondary to abdominal aortic banding and ten sham-operated rats were studed. Result showed that systolic blood pressure and left ventricular end diastolic pressure (LVEDP) rise sharply after operation(85?18 vs 132 + 20 P<0.05),(25? vs 53 + 10 P<0.05). But + dp/dt almost decreased to one-seventh of normalcontrols( dp/dt: 137+24 vs 956 + 20 mmHg/s, -dp/dt: 142 + 18 vs 750 + 66 mmHg/s, p<0.05) .When CP was given alone for the treatment, it could decrease mortality(20% vs 0, p<0.05) .But it coulden't decrease blood pressure and prevent left ventricular hypertrophy(SBP:92+7 vs 93 + 12 mmHg, heart weight/body weight: 4.6+1.0 vs 4.1+0.3 p>0.05). Otherwise, ramipril had these function. But the allied drug using group was the most effective.Conclution: Exogenious CP can reduce the oxidative injury of H2O2, improve heart function and decrease mortality. The mechanism may lie in protecting mitochondrial function, preserving ATP content and reducing apoptosis. In the treatment of rats of myocardial hypertrophy and heart failure, allied drug therapy is more superior than any single drug does.