肝素结合蛋白在成人心脏手术中的应用。

Heparin Binding Protein in Adult Heart Surgery.

机构信息

Division of Anesthesiology, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

出版信息

Ann Thorac Surg. 2019 Apr;107(4):1154-1159. doi: 10.1016/j.athoracsur.2018.10.007. Epub 2018 Nov 14.

DOI:10.1016/j.athoracsur.2018.10.007

PMID:30447193

Abstract

BACKGROUND

Heparin binding protein (HBP) is released from neutrophilic secretory vesicles upon neutrophil adhesion on the endothelium. HBP mediates capillary hyperpermeability experimentally. In sepsis, HBP predicts organ dysfunction. Cardiopulmonary bypass induces neutrophil activation and hyperpermeability. We hypothesized that in cardiopulmonary bypass, HBP is released in the reperfused coronary circulation concomitantly with neutrophil adhesion.

METHODS

In 30 patients undergoing aortic valve replacement, concomitant blood samples were drawn from the coronary sinus and arterial line before aortic cross-clamping and 5 minutes after reperfusion to calculate transcoronary differences. Plasma HBP concentrations, neutrophil markers lactoferrin and myeloperoxidase, myocardial injury marker heart-type fatty acid binding protein, and leukocyte differential counts were measured.

RESULTS

Arterial HBP was 4.1 ng/mL (interquartile range [IQR], 3.6 to 5.3 ng/mL) preoperatively and 150.0 ng/mL (IQR, 108.2 to 188.6 ng/mL) after aortic declamping. HBP increased 39-fold, lactoferrin 16-fold, and myeloperoxidase fourfold during cardiopulmonary bypass. Before cardiopulmonary bypass, there were marginal transcoronary differences in HBP (1.4 ng/mL; IQR, -0.4 to 3.6 ng/mL; p = 0.001) and heart-type fatty acid binding protein (0.4 ng/mL; IQR, -0.04 to 3.5 ng/mL; p = 0.001) but not in the other indicators. During reperfusion, transcoronary HBP release (6.4 ng/mL; IQR, 1.8 to 13.7; ng/mL; p < 0.001) was observed concomitantly with transcoronary neutrophil sequestration (-0.14 × 10/L; IQR, -0.28 to 0.01 × 10/L; p = 0.001) and transcoronary heart-type fatty acid binding protein release (6.9 ng/mL; IQR, 3.0 to 25.8 ng/mL; p < 0.001). There were no transcoronary differences in lactoferrin or myeloperoxidase during reperfusion.

CONCLUSIONS

Cardiopulmonary bypass results in substantial increase in circulating HBP. HBP is also released from the reperfused coronary circulation concomitantly with coronary neutrophil adhesion and myocardial injury. HBP may be one candidate for a humoral factor mediating capillary leak in cardiopulmonary bypass.

摘要

背景

肝素结合蛋白（HBP）在中性粒细胞黏附在内皮细胞上时从中性粒细胞的分泌小泡中释放出来。HBP 实验中介导毛细血管通透性增加。在败血症中，HBP 预测器官功能障碍。体外循环诱导中性粒细胞激活和通透性增加。我们假设在体外循环中，HBP 与中性粒细胞黏附同时在再灌注的冠状循环中释放。

方法

在 30 例行主动脉瓣置换术的患者中，在主动脉夹闭前和再灌注后 5 分钟，同时从冠状窦和动脉导管抽取血样，以计算跨冠状差异。测量血浆 HBP 浓度、中性粒细胞标志物乳铁蛋白和髓过氧化物酶、心肌损伤标志物心脏型脂肪酸结合蛋白和白细胞分类计数。

结果

术前动脉 HBP 为 4.1ng/ml（IQR，3.6-5.3ng/ml），主动脉夹闭后为 150.0ng/ml（IQR，108.2-188.6ng/ml）。HBP 在体外循环中增加了 39 倍，乳铁蛋白增加了 16 倍，髓过氧化物酶增加了 4 倍。体外循环前，HBP（1.4ng/ml；IQR，-0.4-3.6ng/ml；p=0.001）和心脏型脂肪酸结合蛋白（0.4ng/ml；IQR，-0.04-3.5ng/ml；p=0.001）有轻微的跨冠状差异，但其他指标没有。在再灌注期间，观察到跨冠状 HBP 释放（6.4ng/ml；IQR，1.8-13.7ng/ml；p<0.001）与跨冠状中性粒细胞隔离（-0.14×10/L；IQR，-0.28-0.01×10/L；p=0.001）和跨冠状心脏型脂肪酸结合蛋白释放（6.9ng/ml；IQR，3.0-25.8ng/ml；p<0.001）同时发生。再灌注期间，乳铁蛋白或髓过氧化物酶无跨冠状差异。