[Studies on protection and mechanism of tetramethylpyrazine on myocardial injury of rats with DHF].

OBJECTIVE

To study the effects of different doses of tetramethylpyrazine on injury and calcium overload in myocardial cells of diastole heart failure rat model.

METHOD

Diastole heart failure model was established by the coarctation of abdominal aorta. 4 weeks after operation, forty rats with DHF were divided into four groups randomly as follows, model (physiological saline 2 mL), tetramethylpyrazine (40 mg x kg(-1) x d(-1)), tetramethylpyrazine (20 mg x kg(-1) x d(-1)), tetramethylpyrazine (10 mg x kg(-1) x d(-1)), with 10 rats for each group (n = 10), and 10 sham operation rats was taken as control (physiological saline, 2 mL). After 4 weeks administration, cardiac function was determined by catheter. The changes of myocardial ultrastructure were investigated by means of transmission electron microscope. [Ca2+ ]i was measured by laser scanning confocal microscope [LSCM]. Ca(2+) -ATPase activity of mitochondrion was measured by the method of enzymatic reaction chromatometry.

RESULT

Compared with the control group, the rats of operation group have no significant changes on left ventricular systolic pressure (LVSP) and maximal rising rate of ventricular pressure (+dp/dt(max)), but left ventricular end diastolic pressure (LVEDP) increased markedly, maximal delining rate of ventricular pressure (-dp/dt(max)) decreased significantly, left ventricular relax time constant quantity (T) markedly extended, myocardial pathology injured markedly, [Ca2+]i in cardiocyte increased markedly and the Ca(2+) -ATPase activity of myocardial mitochondria decreased significantly in the model group. After 4 weeks administration, compared with the model group, LVEDP decreased significantly, -dp/dt(max) increased markedly, T markedly shortened, myocardial ultrastructure damage were significantly reduced, fluorescent value decreased and Ca(2+) -ATPase activity of mitochondrion increased significantly in TMP low-dose group and mid-dose group.

CONCLUSION

Low dosage of TMP can reduced myocardial pathology injury, increased Ca(2+)-ATPase activity of myocardial mitochondria, improve cardiac function and [Ca2+]i in cardiocyte and antagonise calcium overload of rats with DHF.