左西孟旦在非体外循环下冠状动脉旁路移植术围术期中的心肌保护作用
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摘要
目的探讨左西孟旦在非体外循环下冠状动脉旁路移植术(OPCABG)围术期中的心肌保护作用。方法选择2017年8月至2018年8月于新乡市第一人民医院行OPCABG治疗的患者46例,根据治疗方法分为试验组及对照组,各23例。对照组患者在围术期采用常规药物治疗,以单硝酸异山梨酯注射液扩张冠状动脉、以低分子肝素钙注射液抗凝、以酒石酸美托洛尔片控制基础心率等;试验组在对照组的基础上予以左西孟旦治疗,术前24 h内起始1 h以10μg/kg静脉泵入,后23 h以0. 1μg/(kg·min)静脉泵入。取切皮前(T_1)、桥血管通畅后即刻(T_2)、术后4 h(T_3)、术后12 h(T_4)、术后24 h(T_5)比较两组患者心肌肌钙蛋白I(c Tn I)、肌酸激酶同工酶(CK-MB)和超氧化物歧化酶(SOD);术后1周复查心脏彩色多普勒超声心动图并对比左心室舒张末期内径、左心室射血分数。结果对照组c Tn I、CK-MB在T_1～T_5呈上升趋势,试验组c Tn I、CK-MB在T_1～T_4上升,T_5降低,且对照组上升速度更快(P <0. 05),两组SOD在T_1～T_3降低,对照组下降速度更快(P <0. 05),T_4～T_5上升,试验组上升速度更快(P <0. 05)。两组在组间、时点间、组间·时点间交互作用比较差异均有统计学意义(P <0. 05)。术后1周,两组左心室舒张末期内径均降低,左心室射血分数均升高,试验组左心室舒张末期内径低于对照组[(46. 4±4. 7) mm比(49. 7±3. 8) mm],左心室射血分数高于对照组[(51. 4±4. 7)%比(48. 7±3. 2)%],两组左心室舒张末期内径在组间、组间·时点间交互作用比较差异无统计学意义(P> 0. 05),在时点间比较差异有统计学意义(P <0. 05),两组左心室射血分数在组间比较差异无统计学意义(P> 0. 05),在时点间、组间·时点间交互作用比较差异有统计学意义(P <0. 05)。结论左西孟旦在OPCABG的围术期应用,通过减低c Tn I、CK-MB的上升幅度、促进SOD的回弹,从而保护心肌发挥心肌保护作用。
Objective To investigate the myocardial protective effect of levosimendan in off-pump coronary artery bypass grafting( OPCABG) during perioperative period. Methods A total of 46 patients with OPCABG in Xinxiang First People's Hospital were included in the study. The patients were divided into a trial group and a control group according to their treatment,with 23 cases in each group. The control group was treated with conventional drugs during perioperative period( such as coronary artery dilatation with isosorbide mononitrate injection,anticoagulation with low molecular weight heparins calcium injection,control of baseline heart rate with metoprolol tartrate tablets,etc.). The trial group was treated with levosimendan on the basis of the control group' s regimen. Levosimendan was given to the tiral group within 24 hours before operation: at 24 hours before operation,initial intravenous infusion of 10 μg/kg for 1 hour; later,intravenous infusion of 0. 1 μg/( kg· min) for 23 hours. At the time of before skin incision( T_1),immediately after vascular patency( T_2),4 hours after operation( T_3),12 hours after operation( T_4),and 24 hours after operation( T_5),the cardiac troponin I( c Tn I),creatine kinase isoenzyme( CK-MB) and superoxide dismutase( SOD) in the two groups were compared; color Doppler echocardiography was done one week after operation to compared the left ventricular end-diastolic diameter reduction and left ventricular ejection fraction. Results In the control group,c Tn I and CK-MB increased from T_1 to T_5,the levels of c Tn I and CK-MB increased from T_1 to T_4 and decreased to T_5 in the trial group,and the rising speed of the control group was faster( P < 0. 05). SOD decreased from T_1 to T_3 and increased from T_4 to T_5 in both groups,but the decline rate of the control group was faster( P < 0. 05),while the increase rate of the trial group was faster( P < 0. 05). There were significant diffe-rences in groups,time points and group·time point interaction( P < 0. 05). After one week of the operation,the left ventri-cular end-diastolic diameter decrease and left ventricular ejection fraction increase in both groups,and left ventricular end-diastolic diameter of trial group was higher than that of the control group[( 46. 4 ± 4. 7) mm vs( 49. 7 ± 3. 8) mm],left ventricular ejection fraction increase of trial group was lower than that of the control group[( 51. 4 ± 4. 7) % vs( 48. 7 ±3. 2) %]. There was no significant difference in left ventricular end-diastolic diameter between the two groups and intergroups-time points interaction( P > 0. 05),and there was significant difference between time points( P < 0. 05). There was no significant difference in left ventricular ejection fraction between the two groups( P > 0. 05),and there was significant diffe-rence between time points and intergroups-time points interaction( P < 0. 05). Conclusion The application of levosimendan in the perioperative period of OPCABG can reduce the increase of c Tn I and CK-MB,promote the rebound of SOD,which protected myocardium.
Objective To investigate the myocardial protective effect of levosimendan in off-pump coronary artery bypass grafting( OPCABG) during perioperative period. Methods A total of 46 patients with OPCABG in Xinxiang First People's Hospital were included in the study. The patients were divided into a trial group and a control group according to their treatment,with 23 cases in each group. The control group was treated with conventional drugs during perioperative period( such as coronary artery dilatation with isosorbide mononitrate injection,anticoagulation with low molecular weight heparins calcium injection,control of baseline heart rate with metoprolol tartrate tablets,etc.). The trial group was treated with levosimendan on the basis of the control group' s regimen. Levosimendan was given to the tiral group within 24 hours before operation: at 24 hours before operation,initial intravenous infusion of 10 μg/kg for 1 hour; later,intravenous infusion of 0. 1 μg/( kg· min) for 23 hours. At the time of before skin incision( T_1),immediately after vascular patency( T_2),4 hours after operation( T_3),12 hours after operation( T_4),and 24 hours after operation( T_5),the cardiac troponin I( c Tn I),creatine kinase isoenzyme( CK-MB) and superoxide dismutase( SOD) in the two groups were compared; color Doppler echocardiography was done one week after operation to compared the left ventricular end-diastolic diameter reduction and left ventricular ejection fraction. Results In the control group,c Tn I and CK-MB increased from T_1 to T_5,the levels of c Tn I and CK-MB increased from T_1 to T_4 and decreased to T_5 in the trial group,and the rising speed of the control group was faster( P < 0. 05). SOD decreased from T_1 to T_3 and increased from T_4 to T_5 in both groups,but the decline rate of the control group was faster( P < 0. 05),while the increase rate of the trial group was faster( P < 0. 05). There were significant diffe-rences in groups,time points and group·time point interaction( P < 0. 05). After one week of the operation,the left ventri-cular end-diastolic diameter decrease and left ventricular ejection fraction increase in both groups,and left ventricular end-diastolic diameter of trial group was higher than that of the control group[( 46. 4 ± 4. 7) mm vs( 49. 7 ± 3. 8) mm],left ventricular ejection fraction increase of trial group was lower than that of the control group[( 51. 4 ± 4. 7) % vs( 48. 7 ±3. 2) %]. There was no significant difference in left ventricular end-diastolic diameter between the two groups and intergroups-time points interaction( P > 0. 05),and there was significant difference between time points( P < 0. 05). There was no significant difference in left ventricular ejection fraction between the two groups( P > 0. 05),and there was significant diffe-rence between time points and intergroups-time points interaction( P < 0. 05). Conclusion The application of levosimendan in the perioperative period of OPCABG can reduce the increase of c Tn I and CK-MB,promote the rebound of SOD,which protected myocardium.
引文
[1]蔡怀卿,武恒朝,孙寒松.非体外循环冠状动脉旁路移植术患者手术前后凝血功能的变化[J].中国微创外科杂志,2013,13(8):710-712.
[2]胡国智,罗萍.体外循环和非体外循环下冠状动脉旁路移植术的疗效对比观察[J].医学综述,2015,21(10):1856-4857.
[3]向道康,阎兴治,杨世虞,等.左卡尼汀对体外循环心瓣膜替换术患者心肌的保护作用[J].中华医学杂志,2003,83(21):1887-1890.
[4] Antila S,Kivikko M,Lehtonen L,et al. Pharmacokinetics of levosimendan and its circulating metabolites in patients with heart failure after an extended continuous infusion of levosimendan[J].Br J Clin Pharmacol,2004,57(4):412-415.
[5] DeHert SG, Lorsomradee S, vanden Eede H, et al. A randomized trial evaluating different modalities of levosimendan administration in cardiac surgery patients with myocardial dysfunction[J]. J Cardiothorac Vase Anesth,2008,22(5):699-705.
[6] Nieminen MS,Fruhwald S,Heunks LM,et al.Levosimendan:Current data, clinical use and future development[J]. Heart, Lung Vessel,2013,5(4):227-245.
[7]孙宝莹.左西孟旦在急性心力衰竭治疗中的应用进展[J].中国药房,2011,18(22):1718-4720.
[8] Anastasiadis K, Antonitsis P,Vranis K, et al. Effectiveness of prophylactic levosimendan in patients with impaired left ventricular function undergoing coronary artery bypass grafting:A rando-mized pilot study[J]. Interact Cardiovasc Thorac Surg,2016, 23(5):740-347.
[9] Silvetti S, Nieminen MS. Repeated or intermittent levosimendan treatment in advanced heart failure:An updated meta-analysis[J]. Int J Cardiol,2016,202:138-143.
[10] Alvarez J,Rouzada M,Fernandez AL,et al. Hemodynamic effects of lev-osimendan compared with dobutamine in patients with low cardiac outputafter cardiac surgery[J]. Rev Esp Cardiol, 2006,59(4):338-345.
[11] Xanthos T,Bassiakou E,KoudounaE, et al. Combination pharmacotherapy in the treatment of experimental cardiac arrest[J]. Am J Emerg Med,2009,27(6):651-659.
[12] Scheiermann P,Beiras-Fernandez A,Mutlak H,et al. The protective effects of levosimendan on ischemia/reperfusion injury and apoptosis[J].Recent Pat Cardiovasc Drug Discov,2011,6(1):20-26.
[13] Farmakis D, Alvarez J,Gal TB,et al. Levosimendan beyond inotropy and acute heart failure:Evidence of pleiotropic effects on the heart and other organs:An expert panel position paper[J]. Int J Cardiol, 2016,222:303-312.
[14]姜慧芳,连燕虹,方军,等.左西孟旦对离体大鼠心肌缺血-再灌注损伤的保护作用[J].心脑血管病防治,2009,9(5):344-346.
[15] Yilmaz MB, Grossini E, Silva Cardoso JC,et al. Renal effects of levosimendan:A consensus report[J]. Cardiovasc Drugs Ther,2013,27(6):581-590.
[16] Toller W, Heringlake M, Guarracino F, et al. Preoperative and perioperative use of levosimendan in cardiac surgery:European expert opinion[J]. Inc J Cardiol,2015,184:323-336.
[17] Harrison RW, Hasselblad V,Mehta RH, et al. Effect of levosimendan on survival and adverse events after cardiac surgery:A metaanalysis[J]. J Cardiothorac Vase Anesth, 2013, 27(6):1224-1232.
[18] Landoni G,Mizzi A,Biondi-Zoccai G,et al. Reducing mortality in cardiac surgery with levosimendan:A meta-analysis of randomized controlled trials[J]. J Cardiothorac Vase Anesth,2010,24(1):51-57.
[19] Tritapepe L, De-Santis V, Vitale D,et al. Levosimendan pre-treatment improves outcomes in patients undergoing coronary artery bypass graft surgery[J]. Br J Anaesth, 2009,102(2):198-204.
[20] Follath F,Cleland JG, Just H,et al. Efficacy and safety of intravenous levosimendan compared with dobut amine in severe low-output heart failure(the LIDO study):A randomised double-blind trial[J]. Lancet.2002,360(9328):196-202.
[2]胡国智,罗萍.体外循环和非体外循环下冠状动脉旁路移植术的疗效对比观察[J].医学综述,2015,21(10):1856-4857.
[3]向道康,阎兴治,杨世虞,等.左卡尼汀对体外循环心瓣膜替换术患者心肌的保护作用[J].中华医学杂志,2003,83(21):1887-1890.
[4] Antila S,Kivikko M,Lehtonen L,et al. Pharmacokinetics of levosimendan and its circulating metabolites in patients with heart failure after an extended continuous infusion of levosimendan[J].Br J Clin Pharmacol,2004,57(4):412-415.
[5] DeHert SG, Lorsomradee S, vanden Eede H, et al. A randomized trial evaluating different modalities of levosimendan administration in cardiac surgery patients with myocardial dysfunction[J]. J Cardiothorac Vase Anesth,2008,22(5):699-705.
[6] Nieminen MS,Fruhwald S,Heunks LM,et al.Levosimendan:Current data, clinical use and future development[J]. Heart, Lung Vessel,2013,5(4):227-245.
[7]孙宝莹.左西孟旦在急性心力衰竭治疗中的应用进展[J].中国药房,2011,18(22):1718-4720.
[8] Anastasiadis K, Antonitsis P,Vranis K, et al. Effectiveness of prophylactic levosimendan in patients with impaired left ventricular function undergoing coronary artery bypass grafting:A rando-mized pilot study[J]. Interact Cardiovasc Thorac Surg,2016, 23(5):740-347.
[9] Silvetti S, Nieminen MS. Repeated or intermittent levosimendan treatment in advanced heart failure:An updated meta-analysis[J]. Int J Cardiol,2016,202:138-143.
[10] Alvarez J,Rouzada M,Fernandez AL,et al. Hemodynamic effects of lev-osimendan compared with dobutamine in patients with low cardiac outputafter cardiac surgery[J]. Rev Esp Cardiol, 2006,59(4):338-345.
[11] Xanthos T,Bassiakou E,KoudounaE, et al. Combination pharmacotherapy in the treatment of experimental cardiac arrest[J]. Am J Emerg Med,2009,27(6):651-659.
[12] Scheiermann P,Beiras-Fernandez A,Mutlak H,et al. The protective effects of levosimendan on ischemia/reperfusion injury and apoptosis[J].Recent Pat Cardiovasc Drug Discov,2011,6(1):20-26.
[13] Farmakis D, Alvarez J,Gal TB,et al. Levosimendan beyond inotropy and acute heart failure:Evidence of pleiotropic effects on the heart and other organs:An expert panel position paper[J]. Int J Cardiol, 2016,222:303-312.
[14]姜慧芳,连燕虹,方军,等.左西孟旦对离体大鼠心肌缺血-再灌注损伤的保护作用[J].心脑血管病防治,2009,9(5):344-346.
[15] Yilmaz MB, Grossini E, Silva Cardoso JC,et al. Renal effects of levosimendan:A consensus report[J]. Cardiovasc Drugs Ther,2013,27(6):581-590.
[16] Toller W, Heringlake M, Guarracino F, et al. Preoperative and perioperative use of levosimendan in cardiac surgery:European expert opinion[J]. Inc J Cardiol,2015,184:323-336.
[17] Harrison RW, Hasselblad V,Mehta RH, et al. Effect of levosimendan on survival and adverse events after cardiac surgery:A metaanalysis[J]. J Cardiothorac Vase Anesth, 2013, 27(6):1224-1232.
[18] Landoni G,Mizzi A,Biondi-Zoccai G,et al. Reducing mortality in cardiac surgery with levosimendan:A meta-analysis of randomized controlled trials[J]. J Cardiothorac Vase Anesth,2010,24(1):51-57.
[19] Tritapepe L, De-Santis V, Vitale D,et al. Levosimendan pre-treatment improves outcomes in patients undergoing coronary artery bypass graft surgery[J]. Br J Anaesth, 2009,102(2):198-204.
[20] Follath F,Cleland JG, Just H,et al. Efficacy and safety of intravenous levosimendan compared with dobut amine in severe low-output heart failure(the LIDO study):A randomised double-blind trial[J]. Lancet.2002,360(9328):196-202.