Objective To investigate the protective effects of isovolemic hemodilution with 6% hetastarch (HAES) and
ligustrazine on
myocardium against ischemia/reperfusion injury. Methods Thirty-two healthy male rabbits were anesthetized with 3% pentobarbital 30 mg·kg-1 , tracheotomized and mechanically ventilated. Left femoral artery and vein were cannulated for direct BP monitoring, blood collection and fluid infusion. Chest was opened and myocardial ischemia was produced by temporary ligation of the anterior descending branch of left coronary artery. Myocardial ischemia was confirmed by elevation or depression of S-T segment and /or high T-wave. The animals were randomly divided into 4 equal groups with 8 animals in each group: Ⅰ control group was subjected to 45 min myocardial ischemia followed by 180 min reperfusion without any treatment; Ⅱ hemodilution group in which 9 ml Ⅲ kg-1 blood was removed and blood volume was maintained by simultaneous infusion of equal volume of 6% HAES at 20 min after myocardial ischemia was started; Ⅳ
ligustrazine group received ligustrazine injectio 20 mg·kg-1 iv 20 min before and 40 min after myocardial ischemia was started; Ⅱ hemodilution + ligustrazine group in which hemodilution was performed as in group Ⅲ and ligustrazine injectio was given iv as in group Ⅲ . BP and HR were recorded before during and at the end of myocardial ischemia, and at 30, 60, 120, 180 min of reperfusion. Hct was measured before and after hemodilution. Blood samples were taken for determination of plasma CPK and LDH activities before ischemia (T0), at the end of 45 min ischemia (T1) and at the end of 180 min reperfusion (T2 ) . At the end of the experiment, myocardial tissue 0.2 g was obtained from ischemic and non-ischemic area for determination of myocardial CPK and LDH activities and election microscopic examination. Results (1) In all four groups plasma CPK and LDH activities were
significantly increased after ischemia (T1 ) and were increased further after reperfusion (T2) (P<0.01), but in group Ⅱ and Ⅲ plasma LDH activity was significantly lower than that in control group at T2 and in group Ⅳ both plasma CPK and LDH activities were significantly lower than those in control group at T2. (2) In all four groups myocardial CPK and LDH activities in ischemic area were significantly lower than those in non-ischemic area, but in ischemic area myocardial CPK activity in group Ⅱ , Ⅲ , Ⅳ and LDH activity in group Ⅱ and Ⅳ were significantly higher than those in group Ⅰ . Myocardial CPK activity in ischimic area in group Ⅳ was even significantly higher than that in group Ⅲ . (3) Electron microscopic examination showed that ultrastructure of cardiomyocytes was severely damaged in group Ⅰ . The damage was milder in group Ⅱ and Ⅲ as compared with that in group I . In group IV the ultrastructure of cardiomyocytes was close to normal. Conclusion Both isovolemic hemodilution with 6 % HAES and ligustrazine injectio have protective effects on myocardium against ischemia/reperfusion injury and combination of them provides better protection.