依达拉奉和1,6-二磷酸果糖联合应用对心脏瓣膜置换手术患者的心肌保护作用

Effects of co-administration with edaravone and fructose-1,6-diphosphate on myocardial protection in patients undergoing cardiac valve replacement

目的探讨氧自由基清除剂依达拉奉和能量代谢调节剂1,6-二磷酸果糖(FDP)联合应用在CPB下行心脏瓣膜置换手术患者的心肌保护作用。方法选取ASAⅡ或Ⅲ级、拟在CPB下行二尖瓣置换、主动脉瓣置换和联合瓣膜置换术患者40例。随机均分为对照组(A组)、依达拉奉组(B组)、FDP组(C组)和联合用药组(D组)。A组给予等容量生理盐水;B组将依达拉奉0.5mg/kg一次性加入CPB预充液中;C组于主动脉阻断前15min静脉滴注FDP 200mg/kg;D组为将依达拉奉0.5mg/kg一次性加入CPB预充液中,并于主动脉阻断前15min静脉滴注FDP 200mg/kg。分别于麻醉后切皮前(T1)、主动脉阻断前(T2)、CPB停止后2h(T3)、CPB停止后6h(T4)和术后24h(T5)采集桡动脉血,测定血浆超氧化物歧化酶(SOD)活性、丙二醛(MDA)浓度;血浆肌酸激酶同工酶(CK-MB)活性、肌钙蛋白I(cTnI)的浓度并记录两组临床效果。结果与T1时比较,T2～T4时A组血浆SOD活性明显降低(P<0.05或P<0.01);T3～T5时四组血浆MDA浓度明显升高、CK-MB活性明显升高(P<0.05或P<0.01);T2～T5时四组血浆cTnI浓度明显升高(P<0.05或P<0.01)。与A组比较,T2～T4时B、C、D组血浆SOD活性明显升高(P<0.05);T3、T4时B、C、D组血浆MDA浓度、T3～T5时B、C、D组血浆CK-MB活性明显降低,T3时B、C、D组和T4时B、D组cTnI浓度明显降低(P<0.05或P<0.01)。与D组比较,T3、T4时B、C组血浆cTnI浓度明显升高(P<0.05)。术中多巴胺最大用量、术后24h引流量A组明显多于D组(P<0.05)。结论依达拉奉或FDP单独用药可以减轻心肌缺血-再灌注损伤,两者联合用药作用更加明显。

Objective To investigate the myocardial protection effects of radical scavenger edaravone（MCI-186） combined with fructose-1, 6-diphosphate （FDP） in patients undergoing cardiac valve replacement with cardiopulmonary bypass （CPB）. Methods Forty patients with rheumatic heart disease undergoing mitral, aortic, mitral or aortic valve replacement were randomly divided into four groups： control group （group A）, group MCI-186 g（group B）, group FDP（group C）, MCL186 and FDP combination group（group D, n= 10 each）. The same volume of saline solution was infused intravenously in group A. Group B received edaravone injection 0. 5 mg/kg in cardioplegia solution. 200 mg/kg FDP was intravenously infused before aorta-clamping in group C. Edaravone 0. 5 mg/kg was mixed with CPB priming fluid and FDP 200 mg/kg was given intravenously 15 min before aortic cross clamp in group D. Plasma activity of superoxide dismulase （SOD） and levels of malondialdehyde （MDA）, creatinekinase-MB and cardiac troponin I were measured before skin incision（T1 ）, before aortic-clamping（T2 ）, at 2 h and 6 h after CPB and 24 h postoperative （T3-T5）. Meanwhile, the clinical effectiveness of each group was observed. Results Compared with T1. SOD activity decreased significantly at T2-T4 in group A, while the levels of serum MDA, CK-MB at T3-T5 and cTnI at T2- T5 increased significantly in all groups（P〈0. 05）. Compared with group A, SOD activity at T2-T4 increased significantly, while levels of serum MDA and CK-MB at T3-T5 decreased in other groups, the levels of cTnI in group B,C,D at T3 and in group B,D at T4 were obviously decreased. （P〈0. 05 or P〈0. 01）. The concentration of cTnI in group B and C was obviously higher than that in group D at T3, T4 （P〈0. 05）. The consumption of dopa mine and drainage quantity within 24 h after surgery were much more in group A than those in group D（P〈0.05）. Conclusion Edaravone and FDP has notable protective effect on myocardial ischemia and reperfusion injury, especially when using combined.