摘要
目的：利用先天性心脏病患儿血浆脑利钠肽(BNP)及其前体(NT-pro-BNP)的水平,评价体外循环(CPB)前后先天性心脏病患儿早期心功能的变化,本文重点研究体外循环术中升主动脉阻断时间、术中体温、低温持续时间及CPB时间对心功能的影响。
方法：病例组(心脏病组)来源于2008年7月-2009年1月在武警广东总队医院心胸外科住院的40例先天性心脏病患儿,于CPB前、CPB结束时、术后24小时三个时间点分别采取静脉血3ml,3000转／min离心分离出血浆,置—20℃冰箱保存,对照组静脉血标本来源于30例该院同期门诊健康体检儿童,采用酶联免疫吸附法定量测定心脏病组和对照组血浆BNP及NT-pro-BNP浓度。
结果：心脏病组在CPB前的血浆BNP及NT-pro-BNP分别是315.45±120.45 pg／ml、331.67±131.83 pg/ml,对照组的血浆BNP及NT-pro-BNP分别是11.65±8.66pg/ml53.12±23.90pg/ml,两组比较差异有统计学意义(P=0.000)；心脏病组CPB结束时血浆BNP及NT-pro-BNP分别是165.91±65.65pg/ml、182.50±65.35pg／ml,与CPB前比较,差异有统计学意义(P=0.000)；心脏病组术后24小时血浆BNP及NT-pro-BNP浓度分别是439.08±154.75pg/m、460.29±167.85pg/ml,均较CPB前升高,且与CPB前比较有统计学意义(P=0.000)。应用多元线性回归分析,升主动脉阻断时间因素未筛选出。CPB结束时,血浆BNP浓度与术中体温呈负相关(相关系数R=0.379,偏回归方程Y1=434.042-10.061X1)；血浆NT-pro-BNP浓度与术中低温持续时间呈负相关(R=0.442,Y2=493.096-11.655X2)。术后24小时,血浆BNP浓度与CPB时间呈正相关、与术中低温持续时间呈负相关(R=0.635,Y3=248.38+3.51X3-2.84X4),CPB时间、术中低温持续时间的标准偏回归系数分别为1.302、-0.754,因此CPB时间对术后24小时血浆BNP的作用大于术中低温持续时间；血浆NT-pro-BNP水平与术中低温持续时间呈负相关(R=0.588,Y4= 1523.31-39.8995).术中体温≤28℃组CPB结束时、术后24小时血浆BNP及NT-pro-BNP水平均高于>28℃组,两组差异有统计学意义(P<0.05)。术中降温时间≤40min组和>40min组,比较CPB结束时、术后24小时血浆BNP及NT-pro-BNP水平,术后24小时,≤40min组低于>40min组,两组差异有统计学意义(P<0.05), CPB结束时血浆BNP及NT-pro-BNP水平比较,差异无统计学意义。CPB时间≤60min组CPB结束时、术后24小时血浆BNP及NT-pro-BNP水平均低于>60min组,两组差异有统计学意义(P<0.05)。
结论：利用血浆BNP及NT-pro-BNP水平作为评价早期心功能变化的指标,有利于临床医生及时监测心功能的动态情况,特别是在术后24小时最有帮助,及时使用相应的血管活性药物,防止及纠正低心排、心衰等危险情况的发生,降低先心病患儿术后死亡率。血浆BNP及NT-pro-BNP浓度与术中体温及术中低温持续时间呈负相关,与CPB时间呈正相关。术中控制体温≥28℃以上(低于30℃)、降温时间≦40min、CPB时间≤60min时其血浆BNP及NT-pro-BNP水平相对降低,可认为对心功能具有保护作用。
Objective:To observe the level of (BNP) and its precursor (NT-pro-BNP) before and after the surgery in children with congenital heart disease, and evaluate the early heart function. Focus on research ascending aortic clamp time, intraoperative body temperature, cooling time and CPB time of cardiac function before and after surgery.
Methods:To select 40 cases of children with heart disease lived in the Guangdong Armed Police Corps Hospital from 2008.7 to 2009.1,and acquired the venous blood at pre-CPB, at the end of CPB and 24 hours after CPB repectively, then separated out the plasma and to freeze it in-70℃refrigerator.At the same time choose 30 cases of healthy control in the same period in the hospital and acquired the venous blood. To detect the concentration of (BNP) and its precursor (NT-pro-BNP) of the plasma using the method of enzyme-linked immunosorbent assay.
Results:The concentration of BNP and NT-pro-BNP in the group with heart disease is 315.45±120.45 pg/ml,331.67±131.83 pg/ml, in the control group is 11.65±8.66pg/ml,53.12±23.90pg/ml respectively, the comparetion between the two groups have statistically significance(P= 0.000); the concentration in the end of CPB in the group with heart disease is 165.91±65.65pg/ml,182.50±65.35 pg/ml, compared with the pre-CPB, the difference was statistically significant (P= 0.000); 24 hours after CPB is 439.08±154.75pg/ml,460.29±167.85pg/ml, higher than those in pre-CPB, and compared with the pre-CPB the difference was statistically significant (P= 0.000). Using multiple linear regression analysis, aortic clamping time factor is not selected.At the end of CPB, plasma BNP concentration and intraoperative body temperature were negatively correlated (correlation coefficient R=0.379, partial regression equation Y1= 434.042-10.061X1); plasma NT-pro-BNP concentration and duration of intraoperative hypothermia were a negative correlation (R= 0.442, Y2= 493.096-11.655X2). After 24 hours of the surgery, the plasma BNP concentration was positively correlated with CPB time, and negatively correlated with duration of intraoperative hypothermia (R= 0.635, Y3= 248.38+3.51 X3-2.84X4), the standard deviation of CPB time and duration of intraoperative hypothermia were 1.302 and-0.754, the standard deviation of CPB time was bigger, so the role of CPB time on plasma BNP is greater than the duration of intraoperative hypothermia after 24 hours of the surgery; plasma NT-pro-BNP level was negatively correlation with duration of intraoperative hypothermia (R=0.588, Y4= 1523.31-39.89X5). The plasma of BNP and NT-pro-BNP levels of intraoperative body temperature≦ 28℃group was higher than> 28℃group at the end of CPB and after 24 hours of the surgery, the difference was significant (P <0.05). Comparing the cooling time of surgery, the plasma of BNP and NT-pro-BNP levels of≦40min group after 24 hours of the surgery was lower than>40min group,the difference was statistically significance (P<0.05); the difference was not statistically significant between two groups at the end of CPB. The plasma of BNP and NT-pro-BNP levels of CPB time≦60min group was lower than the CPB time>60min group at the end of CPB and after 24 hours of the surgery, the differences were significant (P<0.05).
Conclusion:1.Using of the plasma of BNP or NT-pro-BNP levels to determine early cardiac function of children with congenital heart disease after cardiopulmonary bypass, it is timely to prevente heart failure and low cardiac output after surgery.2. The plasma of BNP and NT-pro-BNP levels were negatively correlation with operation temperature and the duration of intraoperative hypothermia, were positively correlation with CPB time.During the surgery, control the body temperature≧28℃(below 30℃), the cooling time≦40min and the CPB time≦60min have protective effect on cardiac function.
引文
[1]肖颖彬,陈林,王学锋.浅低温体外循环心脏跳动中心内直视手术1032例临床分析[J],第三军医大学学报,2001,(23)5：502
[2]陈海生,陈景伟,冼明海等.416例婴幼儿体外循环心内直视术后死亡病例分析[J],中华小儿外科杂志,2005,26(10)：530-532
[3]Guido Oppidoa, Carlo Pace Napoleonea, Roberto Formigari, Outcome of cardiac surgery in low birth weight and premature infants, European Journal of Cardio-thoracic Surgery,2004,26: 44-53
[4]胡大一,吴彦.规范心力衰竭的治疗加强患者管理[J].中华心血管杂志.2005,33(6)：495-497
[5]Gantham JA,Borgeson DD,Burnett JC.BNP:pathophysiological and potential therapeutic roles in acute congestive heart failure[J].Am J physiol,1997,272:R1077-83.
[6]Cowie MR, Jounlain P, Maisel A, et al Clinical applications of B-type zmtriuretic optide(B: qP)testing[J].Fur Heart,2003,24(19):1710-1718
[7]Maisel As,Koon J,Krishnaswamy P,et al.utility of B-nutriuretic as a rapid point of care test for screening patients undergoing echocardic graphy to determine left ventricular dysfunction. Am Heart J,2001,141(3):367-374.
[8]Yoshimura M,Yasue H,Okamura K, et al.Different secretion pattern of atrial natriuretic peptide and brain natriuretic peptide in patients with congestive heart filure.Circulation,1993, 87:464-9.
[9]Macda K,Takayosh T,Wada A,Hisanaga T,Kinoshita M.Plasma brain natriuretic peptide as a biochemical marker of high left ventricular end-diastolic pressure in patients with symptomatic left ventricular dysfunction.Am Heart J,1998,135:825-32.
[10]Bakker J, Gies I, Slaveuburg B, et al Reference values for N-terminal pro-B-type natriuretic peptide in umbilical cord blood[J].Clin them,2004,50(12):2465
[11]Lainchbury JG, NichoUs MG, Espiner EA, et al Rehional plasma levels of cardillc peptides and their response to acllte neutraleu, aovcpad~ inhibition in rnan [J]. Clin Sci,1998,95(5):547-555
[12]Bakker J, Gies I, Slaveuburg B, et al Reference values for N-terminal pro-B-type natriuretic peptide in umbilical cord blood[J].Clin them,2004,50(12):2465
[13]Lainchbury JG, Campbell E, Frampton CM, ct al Brain natriuretic peptide and N-terminal brain natriuretic peptide in the diagnosis of heart hilure in patients with acute shortness of breath [J]. J Am Coil Cardiol,2003,42(4):728-735
[14]Huhta JC, Asante-Korang A, Serrano M, et al The ontogeny of biochemical markers of cardiac dysftmcfion[J]. Curt Optin Podiatr,2005,17:563-67
[15]Nasser N, Bar-Oz B, Nir A. Natr1uretic peptides and heart disease fninfants and children [J]. Pediatr,147(2):248.253
[16]Bjoern A. Groenninga, Jens C, et al Evaluation of impaired left ventricular ejection fraction and increased dimensions by multiple neurohumoral plasma concentrations[J].Eur J Heart Fail, 2001,3(6):699-708
[17]Mir TS,Laux R,Hellwege HH,et al Plasma concentrations of aminoterminal pro atrial natriuretic peptide and aminoterminal pro-brain natriuretic peptide in healthy neonates:marked and rapid increase after birth[J].Pediatrics.2003,112:896-899
[18]Mir TS,Flato M, Falkenberg J, et al Plasma concentrations of N-terminal brain natriuretic peptide in healthy children, adolescents, and young adults:effect of age and gender[J].Pediatr Cardiol.2006,27:73-77
[19]Nir A, Baroz B, Perles Z, et al N-terminal pro-B-type natriuretic peptide:reference plasma levels from birth to adolescence; elevated levels at birth and in heart diseases[J].Acta Paodia. 2004,93:603-607
[20]Koch A, Singer H. Normal values of B-type mltiuretic popfide in infants,children,and adolescents[J].Heart,2003,89(8):875-878
[21]Redfield MM,Rodehehler RJ,Jacobson SJ,et al Plasma BNP concentration:impact of age and gender[J].Am Coil Cardiol,2002,40:976-982
[22]Ohuchi H, Takasugi H, Ohashi H, et al Stratification of pediatric heart failure on the basis of neurahormone and cardiac autonomic nervous activities in patients with congenital heart disease[J].Circulation,2003,108:2368-2376
[23]Wieczorek SJ, Wu AH, Christenson R, et al A rapid B-type natriuretic peptide assay accurately diagnoses left ventricular dysfunction and heart failure:a multicenter evaluation [J]. Am Heart,2002,144(5):834-839
[24]Thomas Oosterhof, MDa, et al Effects of Volume and/or Pressure Overload Secondary to Congenital Heart Disease (Tetralogy of Fallot or Pulmonary Stenosis) on Right Ventricular Function Using Cardiovascular Magnetic Resonance and B-Type Natriuretic Peptide Levels [J]. Am cardiol,2006,97:1051-1055
[25]Yokokunii, Masahiro kamada,Shinichi Onstuki,et al Plasma Brain Natriuretic Peptide and the Evaluation of Volume Overload in Infants and Children with Congenital Heart Disease[J]. ActaMed, Okayama,2003,57(4):191-197
[26]Cowley CG, Bradley JD, Stray RE. B-type natriuretic peptide levels in congenital heart disease[J].Pedian Cardiol,2004,25(4):336-340
[27]Holmstrom H, Hall C, Thaulow E. Plasma levels of natriuretic peptides and hemodynamie assessment of patent ductus arteriosus in preterm infants[J]. Acta Paediatr,2001,90(2):184-191
[28]Puddy VF,Amirmans C,Williams AF,et al Plasma brain natriuretic peptide as a predictor of haemodynamically significant patent ductus arteriosus in pretern infants[J].Clin Sci(London), 103:75-77
[29]杨世伟,秦玉明,曹黎明等.动脉导管未闭患儿介入治疗前后血浆N末端脑利钠肽水平及心功能变化[J]；实用儿科临床杂志,2007,22(13)：7
[30]Mir TS, Marohn S, Laer S, et al Plasma concentrations of N-terminal pro-brain natriuretic peptide in control children from the neonatal to adolescent period and in children with congestrive heart failure [J].Pediatrics,2002,110(6):e76
[31]Dao Q,Krishnaswamy P,Kazanegra R,et al Utility of B-Type Natriuretic peptide(BNP)in the Diagnosis of CHF in an urgent Care Setting[J]. Am Coll Cardiol,2001,37:379-385.
[32]Valli N, Georges A, Corcuf JB, et al Assessment of brain natriuretic peptide in patients with suspected heart failure:Comparison with radionuchde ventrleulol tphydata[J].Clin Chim Acta,2001,306(1-2):19-26
[33]Thomas Oosterhof, MDa, Igor I Tulevski, et al Effects of Volume and/or Pressure Overload Secondary to Congenital Heart Disease (Tetralogy of Fallot or Pulmonary Stenosis) on Right Ventricular Function Using Cardiovascular Magnetic Resonance and B-Type Natriuretic Peptide Levels[J]. Am J Cardiol,2006,97:1051-1055
[34]Vrtovec B,Delgado R,Zewail A,et al Prolonged QTc interval and B-type natriuretic peptide levels together predict mortality in patients with advanced heart failure [J].Cireulation,2003, 107(13):1764-1769.
[35]武育蓉,陈树宝,黄美蓉等.氨基末端脑利钠肽前体在室间隔缺损合并心力衰竭诊断中的价值[J].中华儿科杂志,2005,43：161-164
[36]武育蓉,陈树宝,孙锟等.现有儿科心力衰竭诊断标准及脑利钠肽对先天性心脏病合并心力衰竭的诊断价值[J],中华儿科杂志,2006,10(44)：10
[37]Costello J.M.,Backer CL,Checchia PA, et al Alterations in the Natriuretic Hormone System Related to Cardiopulmonary Bypass in Infants with Congestive Heart Failure[J]. Pediatr Cardiol, 2004,25:347-353
[38]李江林,李渝芬,张智伟等.先天性心脏病介入治疗前后脑利钠肽前体水平的比较[J].中国介入心脏病学杂志,2006,5(14)：10
[39]Mair P, Mair J, Bleier J,et al. Augmented release of brain natriuretic peptide during reperfusion ofthe human heart after cardioplegic cardiac arrest. Clin Chim Acta1997;261:57-68.
[40]Morimoto K, Mori T, Ishiguro S, et al. Perioperative changes in plasma brain natriuretic peptide concentrations in patients undergoing cardiac surgery. Surg Today 1998;28:23-9.
[41]Avidan MS, Meehan N, Ponte J, et al. Changes in brain natriuretic peptide concentrations following open cardiac surgery with cardioplegic cardiac arrest. Clin Chim Acta 2001;303:127-32.
[42]Watanabe M, Egi K, Hasegawa S, et al. Significance of serum atrial and brain natriuretic peptide release after coronary artery bypass grafting. Surg Today 2003;33:671-3.
[43]Berendes E, Schmidt C, Van Aken H, et al. A-type and B-type natriuretic peptides in cardiac surgical procedures A. Anesth Analg 2004;98:11-9.
[44]Hutfless R, Kazanegra R, Madani M, et al. Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery. J Am Coll Cardiol 2004;43:1873-9.
[45]Bail DHL, Kofler M, Ziemer G. Brain natriuretic peptide (BNP) in patients undergoing coronary artery bypass grasfting. Thorac Cardiovasc Surg 2004;52:135-40.
[46]Ationu A, Singer DR, Smith A, et al. Studies of cardiopulmonary bypass in children: implications for the regulation of brain natriuretic peptide. Cardiovasc Res 1993;27:1538-41.
[47]Klinge R,Hystad M,Kjek shus J,et al.An experimental study of cardiac natriuetic peptides as markers of development of CHF.Scand J clin Lab invest,1998,58:683-9.
[48]Kalra PR, Anker SD, Costs AJ. Water and sodium regulation in chronic heart failure:the role Of natriuretic peptide and vasopression [J]. Csdinwlse Res,2001,51(3):495-509
[49]Grantham JA,Borgeson DD,Burnett JC.BNP:pathophysiological and potential therapeutic roles in acute congestive heart failure[J].Am J physiol,1997,272:R1077-83.
[50]胡小琴,心血管麻醉及体外循环[J].北京人民卫生出版社,1997,570-572.
[51]姚松朝,李义,解水本,等;体外循环心内直视术期间内源性类洋地黄物质变化的临床研究[J].中华心胸外科杂志：1994；10：33
[52]朱团结,姚筱,廖凡,等;大左心室心脏病患者术后发生室性心律失常的危险因素分析[J].中国胸心血管外科临床杂志;2009;16(2)：110-113.
[53]袁运长,尹帮良,喻风雷,等.心瓣膜置换术后心室颤动的高危因素分析.中国胸心血管外科临床杂志,2002,9(3)：161-164.
[54]周建仓,周晓红,王永清,等.心脏瓣膜置换术后早期严重室性心律失常相关因素分析及其防治.浙江医学,2006,28(2)：113-114
[55]朱秉智,李清泉,秦建伟,等.体外循环心脏手术中心肌保护方法的改进.江苏医药,1997,23：4-6.
[56]沈远仲,陈启福,葛酉新.体外循环与低心输出量综合征.中华胸心血管外科杂志,1989,5：80-81.
[57]朱平,汪曾炜.血停跳液心肌保护作用的实验研究.中华胸.心血管外科杂志,1994,10：348-350.
[58]Koglin J,Pehlivanli S,Schwaiblamir M,et al.Role of brain natriuretic peptide in risk stratification of patients with congestive heart failure. J Am Coll Cardiol,2001,38:1934-1941.
[59]Nagaya N,Nishikimi T,Uematsu M,et al.Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension.Circulation,2000,102:865-870.
[60]Richardson AM,Doughty R,Nicholls MG,et al.Neurohumoral predictors of benefit from carvedilol in ischemic left ventricular dysfunction. Circulation,1999,99:786-797.
[61]Troughton RW,Frampton CM,Yandle TG,Espiner WA,Nhcholls MG,Richards AM. Teatment of heart failure guided byplasma aminoterminal brain natriuretic peptide(N-BNP) concentrations[J].Lancet,2000,355:1126-30.
