Myocardial Protection of Sevoflurane Used in the Whole Process of Cardiopulmonary Bypass：A RandomizControlled Trial HU Qiang，GAO Guo-dong，YU Kun，JIANG Fu-qing，LONG Cun._Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

HU Qiang , GAO Guodong , YU Kun , JIANG Fuqing , LONG Cun.

State Key Laboratory of Cardiovascular Disease，Fu wai Hospital，National Center for Cardiovascular Diseases，Chinese Academy of Medical Sciences and Peking Union Medical College，Beijing 100037，P. R. China;

Corresponding author：

Keywords：

Cardiopulmonary bypass; 　Sevoflurane; 　Myocardial protection; 　Randomized controlled trial

DOI：

10.7507/1007-4848.20130133

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Abstract： Objective To observe myocardial protective effect of sevoflurane used in the whole process of cardiopulmonary bypass（CPB）. Methods A total of 150 patients older than 18 years who underwent cardiac surgery under CPB in Fu wai Hospital from January 2010 to November 2011 were enrolled in this double-blind and randomized controlled study. All the patients were randomly divided into three groups：Sevoflurane pretreatment group （Group A，n=50），whole-process Sevoflurane group （Group B，n=50），and whole-process intravenous anesthesia group （Group C，n=50）. Radial artery pressure and other hemodynamic parameters were continuously measured for all the patients. At following time points: CPB beginning （T1），aortic declamping （T2），3 hours after aortic declamping （T3），and 24 hours after aortic declamping （T4），serum concentrations of cardiac troponin I （cTnI） and other parameters were measured by enzyme-linked immunosorbent assay （ELISA）. Results There were 31 males and 19 females at age of 60.43±3.24 years in group A，28 males and 22 females at age of 59.88±4.12 years in group B，31 males and 19 females at age of 58.76±3.87 years. There was no statistical difference in mean arterial pressure （MAP），central venous pressure （CVP），pulmonary artery wedge pressure （PAWP） and heart rate （HR） at respective time points among the 3 groups （P＞0.05）. At T1 and T2，there was no statistical difference in cardiac index （CI） among the 3 groups （P＞0.05）. At T3，there was no statistical difference in CI between Group A and Group C（F=3.382，P=0.845），but CI of Group B was significantly higher than that of Group A and C（F=3.382，3.382； P=0.033，0.020）. At T4，CI of Group B was significantly higher than that of Group A and C （F=13.324，13.324； P=0.005，P=0.000），and CI of Group A was significantly higher than that of Group C （F=13.324，P=0.024）. At T1 and T2，there was no statistical difference in serum concentrations of creatinine kinase MB （CK-MB），cTnI，interleukin-6 （IL-6） and tumor necrosis factor alpha （TNF-α） among the 3 groups （P＞0.05）. At T3 and T4，serum concentrations of CK-MB，TNF-α，IL-6 and cTnI of Group C were significantly higher than those of Group A，and serum concentrations of CK-MB，TNF-α，IL-6 and cTnI of Group A were significantly higher than those of Group B （F=531.616，5.410，3.5813，3.160，1.126，4.702，7.819，5.424，all P=0.000）. Conclusion Sevoflurane used in the whole process of CPB has definite myocardial protective effect which is ber than that of Sevoflurane pretreatment.

Citation： HU Qiang,GAO Guodong,YU Kun,JIANG Fuqing,LONG Cun.. Myocardial Protection of Sevoflurane Used in the Whole Process of Cardiopulmonary Bypass：A RandomizControlled Trial HU Qiang，GAO Guo-dong，YU Kun，JIANG Fu-qing，LONG Cun.. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2013, 20(4): 435-440. doi: 10.7507/1007-4848.20130133 Copy

1.	Yanar H， Taviloglu K， Ertekin C， et al. Planned second-look laparoscopy in the management of acute mesenteric ischemia. World J Gastroenterol， 2007， 13 （24）：3350-3353.
2.	Bouwman RA， Salic K， Padding FG， et al. Cardioprotection via activation of protein kinase C-delta depends on modulation of thereverse mode of the Na＋- Ca2＋ exchanger. Circulation， 2006， 114（1 Suppl）：I226-I232.
3.	Kevin LG， Novalija E， Riess ML， et al. Sevoflurane exposuregenerates superoxide but leads to decreased superoxide duringischemia and reperfusion in isolated hearts. Anesth Analg， 2003， 96 （4）：949-955.
4.	Chiari P， Bouvet F， Piriou V. Anaesthetic-induced myocardial precon-ditioning：fundamental basis and clinical implications. Ann Fr AnesthReanim， 2005， 24 （4）：383-396.
5.	庄欣琪，吕国义，徐勇，等. P38 MAPK信号转导通路在七氟烷后处理减轻乳鼠心肌细胞缺氧复氧损伤中的作用. 中华麻醉学杂志， 2009， 29 （8）：741–744.
6.	Hu G， Salem MR， Crystal GJ. Role of adenosine receptors in volatileanesthetic preconditioning against neutrophil-induced contractile dysfunction in isolated rat hearts. Anesthesiology， 2005， 103 （2）：287-295.
7.	Krolikowski JG， Bienengraeber M， Weihrauch D， et al. Inhibition of mitochondrial permeability transition enhances isoflurane-induced cardioprotection during early reperfusion：the role of mitochondrial KATP channels. Anesth Analg， 2005， 101 （6）：1590-1596.
8.	Obal D， Dettwiler S， Favoccia C， et al. The influence of mitochondrial KATP-channels in the cardioprotection of preconditioning and postconditioning by sevoflurane in the rat in vivo. Anesth Analg， 2005， 101 （5）：1252-1260.
9.	Chen HT， Yang CX， Li H， et al. Cardioprotection of sevoflurane postconditioning by activating extracellular signal-regulated kinase 1/2 in isolated rat hearts. Acta Pharmacol Sin， 2008， 29 （8）：931-941.
10.	Deyhimy DI， Fleming NW， Brodkin IG， et al. Anesthetic preconditioning combined with postconditioning offers no additional benefit over preconditioning or postconditioning alone. Anesth Analg， 2007， 105 （2）：316-324.
11.	李洪，杨天德，吴悦维，等. 吗啡复合七氟醚预处理对体外循环冠脉搭桥患者术中的心肌保护作用. 重庆医学， 2009， 38 （15）：1873-1875.
12.	王刚，周琪，高长青，等. 吸入麻醉和静脉麻醉下非体外循环冠脉搭桥术血流动力学和心肌缺血研究. 军医进修学院学报， 2006， 27 （5）：384-386.
13.	郭训，刘琴湘，岑欢，等. 心肌肌钙蛋白Ⅰ对心内直视手术心肌损伤的判定价值. 中国体外循环杂志， 2006， 4 （2）：97-99.
14.	Tsang A， Hausenloy DJ， Mocanu MM， et al. Postconditioning：a form of"modified reperfusion. protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway.Circ Res， 2004， 95 （3）：230-232.
15.	Zhao ZQ， Corvera JS， Halkos ME， et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion：comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol， 2003， 285 （2）：H579-H588.
16.	Payne RR. Sevoflurane-induced preconditioning protects againstcerebral ischemic neuronal damage in rats. Brain Res， 2005， 1034 （1-2）：147-152.
17.	Lu X， Liu H， Wang L， et al. Activation of NF-kappaB is a critical element in the antiapoptotic effect of anesthetic preconditioning. Am J Physiol Heart Circ Physiol， 2009， 296 （5）：H1296-H1304.
18.	An J， Rhodes SS， Jiang MT， et al. Anesthetic preconditioning enhances Ca2＋ handling and mechanical and metabolic function elicited by Na＋- Ca2＋ exchange inhibition in isolated hearts.Anesthesiology， 2006， 105 （3）：541-549.
19.	Julier K， da Silva R， Garcia C， et al. Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery：a double-blinded， placebo-controlled， multicenter study. Anesthesiology， 2003， 98 （6）：1315-1327.
20.	M RM， Wang YL， Zhang WS， et al. Emulsified isoflurane producescardiac protection after ischemia-reperfusion Injury in rabbits. AnesthAnalg， 2008， 106 （5）：1353-1359.
21.	Nordlie MA， Wold LE， Simkhovich BZ， et al. Molecular aspects of ischemic heart disease：ischemia/reperfusion-induced genetic changes and potential applications of gene and RNA interference therapy. J Cardiovasc Pharmacol Ther， 2006， 11 （1）：17-30.
22.	朱俊超，马虹，王俊科. 七氟醚对大鼠心肌缺血再灌注损伤的影响. 中华麻醉学杂志， 2009， 29 （1）：91-92.
23.	胡强，马剑，姜福清，等. 七氟烷用于体外循环对手术室环境污染的研究. 实用临床医药杂志， 2011， 15 （11）：11-14.
24.	Landoni G， Fochi O， Tritapepe L， et al. Cardiac protection by volatile anesthetics. A review. Curr Vasc Pharmacol， 2009， 75 （5）：269-273.
25.	Cromheecke S， Pepermans V， Hendrickx E， et al. Cardioprotective properties of sevoflurane in patients undergoing aortic valve replacement with cardiopulmonary bypass. Anesth Analg， 2006， 103 （2）：289-296.
26.	De Hert SG， Broecke PW， Mertens E， et al. Sevoflurane but not propofol preserves myocardial function in coronary surgery patients. Anesthesiology， 2002， 97 （1）：42-49.
27.	De Hert SG， Van der Linden PJ， Cromheecke S， et al. Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration. Anesthesiology， 2004， 101 （2）：299-310.
28.	刘悦，刘雅，张瑾，等. 七氟烷后处理联合七氟烷预处理对急性心肌缺血-再灌注大鼠血浆SOD及MDA的影响. 河北医药， 2011， 33 （3）：329-331.

1. 　Yanar H， Taviloglu K， Ertekin C， et al. Planned second-look laparoscopy in the management of acute mesenteric ischemia. World J Gastroenterol， 2007， 13 （24）：3350-3353.
2. 　Bouwman RA， Salic K， Padding FG， et al. Cardioprotection via activation of protein kinase C-delta depends on modulation of thereverse mode of the Na＋- Ca2＋ exchanger. Circulation， 2006， 114（1 Suppl）：I226-I232.
3. 　Kevin LG， Novalija E， Riess ML， et al. Sevoflurane exposuregenerates superoxide but leads to decreased superoxide duringischemia and reperfusion in isolated hearts. Anesth Analg， 2003， 96 （4）：949-955.
4. 　Chiari P， Bouvet F， Piriou V. Anaesthetic-induced myocardial precon-ditioning：fundamental basis and clinical implications. Ann Fr AnesthReanim， 2005， 24 （4）：383-396.
5. 　庄欣琪，吕国义，徐勇，等. P38 MAPK信号转导通路在七氟烷后处理减轻乳鼠心肌细胞缺氧复氧损伤中的作用. 中华麻醉学杂志， 2009， 29 （8）：741–744.
6. 　Hu G， Salem MR， Crystal GJ. Role of adenosine receptors in volatileanesthetic preconditioning against neutrophil-induced contractile dysfunction in isolated rat hearts. Anesthesiology， 2005， 103 （2）：287-295.
7. 　Krolikowski JG， Bienengraeber M， Weihrauch D， et al. Inhibition of mitochondrial permeability transition enhances isoflurane-induced cardioprotection during early reperfusion：the role of mitochondrial KATP channels. Anesth Analg， 2005， 101 （6）：1590-1596.
8. 　Obal D， Dettwiler S， Favoccia C， et al. The influence of mitochondrial KATP-channels in the cardioprotection of preconditioning and postconditioning by sevoflurane in the rat in vivo. Anesth Analg， 2005， 101 （5）：1252-1260.
9. 　Chen HT， Yang CX， Li H， et al. Cardioprotection of sevoflurane postconditioning by activating extracellular signal-regulated kinase 1/2 in isolated rat hearts. Acta Pharmacol Sin， 2008， 29 （8）：931-941.
10. 　Deyhimy DI， Fleming NW， Brodkin IG， et al. Anesthetic preconditioning combined with postconditioning offers no additional benefit over preconditioning or postconditioning alone. Anesth Analg， 2007， 105 （2）：316-324.
11. 　李洪，杨天德，吴悦维，等. 吗啡复合七氟醚预处理对体外循环冠脉搭桥患者术中的心肌保护作用. 重庆医学， 2009， 38 （15）：1873-1875.
12. 　王刚，周琪，高长青，等. 吸入麻醉和静脉麻醉下非体外循环冠脉搭桥术血流动力学和心肌缺血研究. 军医进修学院学报， 2006， 27 （5）：384-386.
13. 　郭训，刘琴湘，岑欢，等. 心肌肌钙蛋白Ⅰ对心内直视手术心肌损伤的判定价值. 中国体外循环杂志， 2006， 4 （2）：97-99.
14. 　Tsang A， Hausenloy DJ， Mocanu MM， et al. Postconditioning：a form of"modified reperfusion. protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway.Circ Res， 2004， 95 （3）：230-232.
15. 　Zhao ZQ， Corvera JS， Halkos ME， et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion：comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol， 2003， 285 （2）：H579-H588.
16. 　Payne RR. Sevoflurane-induced preconditioning protects againstcerebral ischemic neuronal damage in rats. Brain Res， 2005， 1034 （1-2）：147-152.
17. 　Lu X， Liu H， Wang L， et al. Activation of NF-kappaB is a critical element in the antiapoptotic effect of anesthetic preconditioning. Am J Physiol Heart Circ Physiol， 2009， 296 （5）：H1296-H1304.
18. 　An J， Rhodes SS， Jiang MT， et al. Anesthetic preconditioning enhances Ca2＋ handling and mechanical and metabolic function elicited by Na＋- Ca2＋ exchange inhibition in isolated hearts.Anesthesiology， 2006， 105 （3）：541-549.
19. 　Julier K， da Silva R， Garcia C， et al. Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery：a double-blinded， placebo-controlled， multicenter study. Anesthesiology， 2003， 98 （6）：1315-1327.
20. 　M RM， Wang YL， Zhang WS， et al. Emulsified isoflurane producescardiac protection after ischemia-reperfusion Injury in rabbits. AnesthAnalg， 2008， 106 （5）：1353-1359.
21. 　Nordlie MA， Wold LE， Simkhovich BZ， et al. Molecular aspects of ischemic heart disease：ischemia/reperfusion-induced genetic changes and potential applications of gene and RNA interference therapy. J Cardiovasc Pharmacol Ther， 2006， 11 （1）：17-30.
22. 　朱俊超，马虹，王俊科. 七氟醚对大鼠心肌缺血再灌注损伤的影响. 中华麻醉学杂志， 2009， 29 （1）：91-92.
23. 　胡强，马剑，姜福清，等. 七氟烷用于体外循环对手术室环境污染的研究. 实用临床医药杂志， 2011， 15 （11）：11-14.
24. 　Landoni G， Fochi O， Tritapepe L， et al. Cardiac protection by volatile anesthetics. A review. Curr Vasc Pharmacol， 2009， 75 （5）：269-273.
25. 　Cromheecke S， Pepermans V， Hendrickx E， et al. Cardioprotective properties of sevoflurane in patients undergoing aortic valve replacement with cardiopulmonary bypass. Anesth Analg， 2006， 103 （2）：289-296.
26. 　De Hert SG， Broecke PW， Mertens E， et al. Sevoflurane but not propofol preserves myocardial function in coronary surgery patients. Anesthesiology， 2002， 97 （1）：42-49.
27. 　De Hert SG， Van der Linden PJ， Cromheecke S， et al. Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration. Anesthesiology， 2004， 101 （2）：299-310.
28. 　刘悦，刘雅，张瑾，等. 七氟烷后处理联合七氟烷预处理对急性心肌缺血-再灌注大鼠血浆SOD及MDA的影响. 河北医药， 2011， 33 （3）：329-331.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Myocardial Protection of Sevoflurane Used in the Whole Process of Cardiopulmonary Bypass：A RandomizControlled Trial HU Qiang，GAO Guo-dong，YU Kun，JIANG Fu-qing，LONG Cun.

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