心脏手术围术期心肌损伤患者冠状动脉循环内NE与MPO的变化

Prognostic value of perioperative change of neutrophil elastase and myeloperoxidase in coronary circulation on perioperative myocardial injury and clinical outcome of patients underwent surgical valve replacement

目的研究心脏手术围术期心肌损伤患者冠状动脉循环内髓过氧物酶(MPO)与中性粒细胞弹性蛋白酶(NE)的变化及其临床意义。方法该研究为前瞻性队列研究,入选2021年6月至2022年6月在南京鼓楼医院及北京阜外医院行外科瓣膜置换手术的患者。发生围术期心肌损伤的患者为心肌损伤组。在未发生心肌损伤的患者中依据年龄、性别及术式按1∶1的比例匹配对照组。其中围术期心肌损伤定义为术后第1天心肌肌钙蛋白T(cTnT)>0.8μg/L,且术后第2天的cTnT水平相较于第1天增加10%以上。术中分别于阻断升主动脉前及开放升主动脉后5 min内,从患者冠状静脉窦口采集血标本,测量MPO及NE水平。记录患者住院期间死亡、恶性室性心律失常、肺炎、二次气管插管、二次手术发生情况,术后体外膜肺氧合(ECMO)、主动脉内球囊反搏(IABP)、连续性肾脏替代治疗(CRRT)使用情况及呼吸机使用时间、重症监护室(ICU)滞留时间。比较心肌损伤组与对照组的MPO及NE水平以及临床结局发生率,采用多因素logistic回归分析心肌损伤的影响因素。结果共入选130例患者,年龄(60.6±7.6)岁,男性59例(45.4%),心肌损伤组及对照组各65例。住院期间,两组均无死亡、使用ECMO、IABP及CRRT病例;与对照组比较,心肌损伤组患者恶性室性心律失常[13.8%(9/65)比3.1%(2/65),P=0.03]、肺炎[20.0%(13/65)比3.1%(2/65),P=0.03]、二次气管插管[6.2%(4/65)比0,P=0.04]发生率更高,术后呼吸机使用时间[16.8(10.7,101.7)h比7.5(4.7,15.1)h,P<0.01]、ICU滞留时间[3.7(2.7,18.9)d比2.7(1.8,6.9)d,P<0.01]更长。主动脉阻断前两组冠状静脉窦血中的MPO及NE水平差异均无统计学意义(P均>0.05)。但主动脉开放后5 min心肌损伤组冠状静脉窦血中的MPO[(551.3±124.2)μg/L比(447.2±135.9)μg/L,P<0.01]及NE[(417.0±83.1)μg/L比(341.0±68.3)μg/L,P<0.01]水平明显高于对照组。多因素logistic回归分析结果显示主动脉开放后5 min冠状静脉窦血中NE(OR=1.02,95%CI:1.01~1.02,P<0.01)、MPO(OR=1.00,95%CI:1.00~1.01,P=0.02)水平及呼吸机使用时间(OR=1.03,95%CI:1.01~1.06,P=0.02)是外科瓣膜置换术后患者出现心肌损伤的独立影响因素。结论心脏手术围术期心肌损伤可导致预后不良,冠状动脉循环内NE及MPO是心脏手术围术期心肌损伤的独立危险因素。

Objective To investigate the clinical value of observing perioperative changes of myeloperoxidase(MPO)and neutrophil elastase(NE)in coronary artery circulation in patients underwent valve replacement surgery.Methods This perspective cohort study was performed in patients who underwent valvular surgery in Nanjing Drum Tower Hospital and Fuwai Hospital from June 2021 to June 2022.Patients were divided into perioperative myocardial injury group and age-,sex-and type of cardiac procedure-matched non-perioperative myocardial injury control group in the ratio of 1∶1.Perioperative myocardial injury was defined as cardiac troponin T(cTnT)>0.8μg/L on the first postoperative day(POD),and the cTnT level on the second POD increased by more than 10%compared with the cTnT level on the first POD.During the operation,blood samples were collected from the coronary sinus before clamping ascending aorta,and within 5 minutes after de-clamping ascending aorta.Then,the levels of MPO and NE on coronary sinus were continuously measured.The death,severe ventricular arrhythmia,pneumonia,re-intubation,repeat cardiac surgery,extracorporeal membrane oxygenation(ECMO),intra-aortic balloon pump(IABP),continuous renal replacement therapy(CRRT),mechanical ventilation time and the duration of intensive care unit(ICU)were recorded.The levels of MPO and NE and the incidence of clinical outcomes were compared between the myocardial injury group and the control group.The independent risk factors of myocardial injury were analyzed by multivariate logistic regression.Results A total of 130 patients were enrolled,aged(60.6±7.6)years old,with 59 males(45.4%).There were 65 patients in the myocardial injury group and 65 patients in the control group.During hospitalization,there was no death,ECMO,IABP and CRRT cases in both groups.Compared with the control group,the incidence of severe ventricular arrhythmia(13.8%(9/65)vs.3.1%(2/65),P=0.03),pneumonia(20.0%(13/65)vs.3.1%(2/65),P=0.03),re-intubation(6.2%(4/65)vs.0,P=0.04)was significantly higher in myocardial injury group.The mechanical ventilation time(16.8(10.7,101.7)h vs.7.5(4.7,15.1)h,P<0.01),and the duration of ICU(3.7(2.7,18.9)vs.2.7(1.8,6.9)d,P<0.01)were significantly longer in myocardial injury group compared with the control group.There was no significant difference in the levels of MPO and NE in coronary sinus blood between the two groups before aortic clamping(all P>0.05).However,MPO((551.3±124.2)μg/L vs.(447.2±135.9)μg/L,P<0.01)and NE((417.0±83.1)μg/L vs.(341.0±68.3)μg/L,P<0.01)after 5 min aortic de-clamping were significantly higher in myocardial injury group than in the control group.Multivariate logistic regression analysis showed that the levels of NE(OR=1.02,95%CI:1.01-1.02,P<0.01),MPO(OR=1.00,95%CI:1.00-1.01,P=0.02)and mechanical ventilation time(OR=1.03,95%CI:1.01-1.06,P=0.02)were independent risk factors of myocardial injury in patients after surgical valvular replacement.Conclusion Perioperative myocardial injury is related poor clinical outcomes,perioperative NE and MPO in coronary artery circulation are independent risk factors of perioperative myocardial injury in patients undergoing valve replacement surgery.