The Protective Effect Of Fasudil Hydrochloride Against Myocardial Ischemia/reperfusion Injury In Patients Undergoing Mitral Valve Replacement With Cardiopulmonary Bypass(CPB)

Objective:To evaluate the protective effect of Fasudil Hydrochloride against myocardial ischemia/reperfusion injury in patients undergoing mitral valve replacement with cardiopulmonary bypass(CPB).Methods: Forty patients whose cardiac function( NYHA) classification were level Ⅱ-Ⅲ, ages were between 31-69, underwent mitral valve replacement with CPB were randomly divided into two groups, test group(n=20)and control group(n=20). The patients in test group received Fasudil Hydrochloride injection(1mg/kg) in the cardioplegic solution of cardiopulmonary bypass; while those in control group received the same volume of 0.9%normal saline. The other treatment methods and medication usages were the same.At five time points were after anesthesia induction before operation(T1), c a r d i o p u l mo n a r y b y p a s s e n d i m m e d i a t e l y( T 2), f o u r h o u r s a f t e r cardiopulmonary bypass end(T3), eight hours after cardiopulmonary bypass end(T4) and twenty-four hours after cardiopulmonary bypass end(T5) radial artery blood samples were extracted to determinate the concentration of lactate dehydrogenase(LDH), creatine kinase isoenzyme(CK-MB), troponin I(c Tn I)in plasma. Myocardial samples in the ischemia region of right atrial appendage were selected ten minutes after opening aorta and used to undergo flow cytometry to detect cell apoptosis rate. And the CPB time, aortic occlusion time, assisted circulation time, the incidence of spontaneous recovery of heart rhythm, temporary pacemaker implantation intraoperative and the average dose of dopamine in twenty-four hours after operation of two groups of patients were recorded.Results:1 There was no statistically significant difference between the two groups in gender, age, weight, preoperative heart function classification and ejection fraction(P>0.05).2 There was no statistically significant difference between the two groups in the cardiopulmonary bypass time,aortic occlusion time, assisted circulation time(P>0.05).3 The incidence of spontaneous recovery of heart rhythm after aorta unclamping in test group was 100%, which in control group was 75%. The incidence of spontaneous recovery of heart rhythm in test group was higher than that in control group, the difference between two groups was statistically significant(P<0.05).4 The case of temporary pacemaker implantation during operation in test group was zero, however the case in control group was one. The case of temporary pacemaker implantation during operation in test group was lower than that in control group, but there was no statistically significant difference between two groups(P>0.05).5 The average dose of dopamine in twenty-four hours after operation in test group was 5.53±2.40ug/kg/min and that in control group was 9.61±3.22 ug/kg/min. The average dose of dopamine in 24 hours after operation in test group was lower than that in control group, the difference between the two groups was statistically significant(P<0.01).6 The comparison of detection results of the lactate dehydrogenase(LDH) in plasma: The concentrations of lactate dehydrogenase( LDH) in plasma of the two groups at T1 time were within the normal ranges. There was no statistically significant difference between the two groups( P>0.05). The concentrations of lactate dehydrogenase( LDH) in plasma of the two groups at T2, T3, T4, T5 time were higher than those at T1 time.The difference within group was statistically significant( P<0.01). The concentrations of lactate dehydrogenase( LDH) in plasma of test group at T2, T3 time were lower than those of control group. But there was no statistically significant difference between the two groups. The concentrations of lactate dehydrogenase( LDH) in plasma of test group at T4, T5 time were lower than those of control group. The differences between the two groups were statistically significant(P<0.01).7 The comparison of detection results of the creatine kinase isoenzyme( CK-MB) in plasma: The concentrations of creatine kinase isoenzyme(CK-MB) in plasma of the two groups at T1 time were within the normal ranges. There was no statistically significant difference between the two groups(P>0.05). The concentrations of creatine kinase isoenzyme(CK-MB) in plasma of the two groups at T2, T3, T4, T5 time were higher than those at T1 time.The difference within group was statistically significant(P<0.01).The concentration of creatine kinase isoenzyme( CK-MB) in plasma of test group at T2 time was lower than that of control group. But there was no statistically significant difference between the two groups. The concentrations of creatine kinase isoenzyme( CK-MB) in plasma of test group at T3, T4, T5 time were lower than those of control group. The differences between the two groups were statistically significant(P<0.05 & P<0.01).8 The comparison of detection results of the troponin I(c Tn I) in plasma: The concentrations of troponin I(c Tn I) in plasma of the two groups at T1 time were within the normal ranges.There was no statistically significant difference between the two groups(P>0.05). The concentrations of troponin I(c Tn I) in plasma of the two groups at T2, T3, T4, T5 time were higher than those at T1 time. The difference within group was statistically significant(P<0.01).The concentration of troponin I(c Tn I) in plasma of test group at T2 time was lower than that of control group. But there was no statistically significant difference between the two groups. The concentrations of troponin I(c Tn I) in plasma of test group at T3, T4, T5 time were lower than those of control group. The differences between the two groups were statistically significant(P<0.01).9 The test of cardiomyocyte apoptosis rate: The rate of cardiomyocyte apoptosis in test group was 7.48±2.18%, which in control group was 12.73±2.74%. The rate of cardiomyocyte apoptosis in test group was lower than that in control group, the difference between the the two groups wasstatistically significant(P<0.01).Conclusions: Fasudil Hydrochloride can decrease the levels of lactate dehydrogenase(LDH), creatine kinase isoenzyme(CK- MB) and troponin I( c Tn I)in plasma, inhibit of cardiomyocyte apoptosis and relieve myocardial ischemia /reperfusion injury, thereby significantly reduce the damage of myocardial cells and tissues. It has protective effects on myocardial protection in patients undergoing mitral valve replacement with cardiopulmonary bypass(CPB).