基于磁悬浮驱动原理的肝移植静脉-静脉转流装置的临床前评价

Preclinical evaluation of a veno-venous bypass device for liver transplantation based on the principle of magnetic levitation drive

目的探讨基于磁悬浮驱动原理自制的肝移植静脉-静脉转流(VVB)装置的性能。方法实验研究,研究时间为2020年8月至2022年1月。实验动物为8头巴马小型猪,在阻断其肝门静脉和肝下下腔静脉后,行肝门静脉-股静脉-颈内静脉的转流,根据应用的转流装置不同将动物分为两组,A组(n=5)使用自制静脉转流装置,B组(n=3)使用进口静脉转流装置。比较两组动物在血管阻断前、血管阻断时、VVB开始后30 min、60 min、90 min和血管开放后30 min共6个时间点的血流动力学变化;比较两组动物的血液相容性指标、肠损伤指标、肾损伤指标及内环境指标在各时点的变化情况。两组间非重复测量的定量资料的比较采用独立样本t检验,两组间重复测量的定量资料的比较采用重复测量方差分析。结果两种装置在转流期间,静脉引流均较充分,主要表现为巴马小型猪的肠管颜色红润、蠕动正常,尿量正常。两组间各时点的血流动力学、血液损伤指标、肠损伤指标、肾损伤指标、中性粒细胞明胶酶相关脂质运载蛋白及内环境指标的差异均无统计学意义(P值均>0.05)。其中A组和B组转流结束肝血管开放后30 min各项指标如下:平均动脉压为(71.0±7.7)mmHg(1 mmHg=0.133 kPa)和(74.0±8.7)mmHg,中心静脉压为(7.0±1.4)cmH_(2)O(1 cmH_(2)O=0.098 kPa)和(7.7±0.6)cmH_(2)O,心率为(131±10)次/min和(132±8)次/min;红细胞计数为(6.43±0.89)×10^(12)/L和(6.32±0.58)×10^(12)/L,血红蛋白为(108.4±5.9)g/L和(110.0±3.5)g/L,游离血红蛋白为(78.28±3.96)mg/L和(78.08±4.54)mg/L;肠脂肪酸结合蛋白为(2.27±0.49)μg/L和(2.40±0.78)μg/L;肌酐为(68.30±9.77)μmol/L和(79.90±26.91)μmol/L,尿素氮为(3.94±1.39)mmol/L和(3.45±0.65)mmol/L;中性粒细胞明胶酶相关脂质运载蛋白为(4.02±0.53)μg/L和(3.86±0.23)μg/L;pH值为7.27±0.04和7.23±0.03,乳酸为(6.18±2.62)mmol/L和(4.30±0.50)mmol/L,Na^(+)为(136.3±3.0)mmol/L和(137.6±1.6)mmol/L,K^(+)为(3.89±0.42)mmol/L和(3.98±0.17)mmol/L,Ca^(2+)为(1.40±0.03)mmol/L和(1.40±0.04)mmol/L;各指标的差异均无统计学意义(P值均>0.05)。结论自制便携式静脉转流装置能安全有效地应用于巴马小型猪的VVB,且可达到与进口装置相似的性能。

Objective To explore the performance of a self-made venous-venous bypass(VVB)device for liver transplantation based on the principle of magnetic levitation drive.Methods Experimental study was conducted from August 2020 to January 2022.Eight Bama minipigs underwent VVB of hepatic portal vein-femoral vein-internal jugular vein after occlusion of hepatic portal vein and inferior vena cava.The animals were divided into two groups according to the VVB devices used during VVB.A self-made VVB device was used in group A(n=5),and an imported VVB device was used in group B(n=3).The hemodynamic changes of the two groups of animals were compared at 6 time points including before vascular occlusion,during vascular occlusion,30 minutes,60 minutes,90 minutes after the start of VVB,and 30 minutes after vascular opening.In addition,the changes of blood compatibility indexes,intestinal injury indexes,kidney injury indexes and internal environment indexes of the two groups of animals at each time point were compared.The independent samples t test was used for the quantitative data between the two groups with non-repeated measures,and the repeated measures analysis of variance was used for the quantitative data between the two groups with repeated measures.Results During the VVB of the two devices,the venous drainage was sufficient,and the main manifestations were that the color of the intestine of the Bama miniature pig was ruddy,the peristalsis was normal,and the urine output was normal.There were no significant differences in hemodynamics,blood injure indexes,intestinal injury indexes,kidney injury indexes,neutropil gelatinase-associated lipocalin,and internal environment indexes(all P>0.05).The indexes at 30 minutes after vascular opening in the group A and the group B were as follows:mean arterial pressure were(71.0±7.7)mmHg(1 mmHg=0.133 kPa)and(74.0±8.7)mmHg,central venous pressure were(7.0±1.4)cmH_(2)O(1 cmH_(2)O=0.098 kPa)and(7.7±0.6)cmH_(2)O,heart rate were(131±10)beats/minutes and(132±8)beats/minutes;red blood cell count were(6.43±0.89)×10^(12)/L and(6.32±0.58)×10^(12)/L,hemoglobin were(108.4±5.9)g/L and(110.0±3.5)g/L,free hemoglobin were(78.28±3.96)mg/L and(78.08±4.54)mg/L;intestinal fatty acid binding protein were(2.27±0.49)μg/L and(2.40±0.78)μg/L;creatinine were(68.30±9.77)μmol/L and(79.90±26.91)μmol/L,blood urea nitrogen were(3.94±1.39)mmol/L and(3.45±0.65)mmol/L;neutropil gelatinase-associated lipocalin were(4.02±0.53)μg/L and(3.86±0.23)μg/L;pH value were 7.27±0.04 and 7.23±0.03,lactic acid were(6.18±2.62)mmol/L and(4.30±0.50)mmol/L,concentrations of Na+were(136.3±3.0)mmol/L and(137.6±1.6)mmol/L,concentrations of K+were(3.89±0.42)mmol/L and(3.98±0.17)mmol/L,concentrations of Ca2+were(1.40±0.03)mmol/L and(1.40±0.04)mmol/L;all indexes in the two group had no differences(all P>0.05).Conclusion The self-made venous bypass device can be safely and effectively applied to VVB of Bama minipigs,and achieves the same performance as the imported venous bypass device.