The protection of the Caspase-3 inhibitor on cardiopulmonary bypass-induced cardiac function injury in the rabbit model

Abstract

Objective To investigate the protection of the Caspase-3 inhibitor (Ac-DEVD-CHO) on cardiopulmonary bypass (CPB)-induced ischemia reperfusion injury in the rabbit model.Methods Rabbits were divided into two groups:control (C) group and Ac-DEVD-CHO (A) group.In the C and A groups,animals underwent CPB at a flow rate of 50-70 ml/kg per min,Ac-DEVD-CHO (5 ml/kg) was administered to the A group rabbits by intravenous injection 30 min before operation and Ac-DEVD-CHO (5 ml/kg) was administered by intravenous infusion while reperfusion being done.The myeloperoxidase (MPO) and Caspase-3 activity,the blood creatine kinase isoenzyme MB (CK-MB) and cardiac troponin Ⅰ (cTnⅠ) in each group were detected.Results A comparison between A group and C group showed that for treated group,the levels of CK-MB (U/L) (111.39 ± 0.03,134.26 ± 3.45,342.49 ± 5.35,501.25 ±8.31 vs.100.41 ± 0.02,435.21 ± 6.38,987.32 ± 25.17,1 264.53 ± 22.08) and cTnⅠ (g/L) (0.03 ±0.02,0.03±0.06,0.08±0.04,0.09±0.02 vs.0.03 ±0.01,0.06±0.03,0.12±0.05,0.17±0.07)were both decreased,the activity of Caspase-3 (z/pmol/h/mg) (0.03 ±0.01,0.09 ±0.02,0.18 ±0.03,0.39±0.02 vs.0.02±0.01,0.16 ±0.05,0.72 ±0.04,0.87 ±0.06) and MPO(μg/L) (0.33±0.02,0.53 ±0.03,0.67 ±0.03,0.88 ±0.05 vs.0.33 ± 0.01,0.96 ±0.04,1.12 ±0.03,2.17 ±0.02) were inhibited (F =36.10-574.13,P ＜ 0.05).The differences of the above items were of statistically significant.Conclusion Ac-DEVD-CHO inhibited the changes in the MPO and Caspase-3 activity and decreased the blood CK-MB and cTnⅠ in simulated extracorporeal circulation.This study suggests that Ac-DEVD-CHO could be feasible therapeutic strategy to protect the cardiac function injury in patients undergoing cardiopulmonary bypass. Key words: The Caspase-3 inhibitor; Cardiopulmonary bypass; Creatine kinase isoenzyme MB ; Cardiac troponin Ⅰ ; Caspase-3 activity ; Myeloperoxidase