定量化肝门血流限制器的研发以及在肝脏切除手术中的应用研究

发布时间：2018-11-23 17:39

【摘要】：目的：探讨肝脏切除手术中血流限流最佳比例，以期在减少除术中出血的同时，降低入肝血流限制带来的肝脏功能损害以及对全身系统性的不良影响，降低手术并发症，改善生存及预后。方法：1.根据肝门解剖结构及血流特点，设计定量化肝门血流限制装置，经权威部门认证，研发、生产并用于动物实验；2.应用定量化肝门血流限制器，研究不同限流比例下，对兔肝脏灌注的影响；3.构建肝切除兔模型，阻断肝动脉，在不同门静脉限流比例下，进行左叶、中叶肝切除，统计术中失血量，术后6h、3d、7d肝功能变化以及7天生存率，探讨肝切除条件下，门静脉最佳限流比例。结果：1.定量化肝门血流限制器获得国家知识产权局认可，授予实用新型专利。2.在肝动脉夹闭、门静脉限流兔模型中，门静脉血流量同肝脏灌注压呈线性正相关，线性回归方程：①绝对值：P（Pu）=85.825+2.051V（ml/min）。②百分比：P（Pu%）=0.296+0.662V（ml min-1%）（上述各方程各常量及回归系数p均0.01）。肝静脉血液回流维持肝脏灌注压的贡献比例约为29.6%。3.在兔肝切除（左叶、中叶）模型中，完全阻断肝动脉，门静脉限流45min：完全阻断、限流90%、80%、70%和完全开放，7天生存率分别为0%、10%、60%、80%、100%。4.在兔肝切除（左叶、中叶）模型中，完全阻断肝动脉，门静脉限流30min：（1）在术中失血方面，限流80%同完全阻断在术中失血量上没有显著差异。（2）在肝损伤方面，通过分析术后肝脏病理和血清肝酶学水平，，肝细胞损伤无论限流比例如何，术后6h损伤达到高峰，之后随着术后时间逐渐恢复；限流70%同完全开放没有显著性差异（P0.05），限流超过80%损伤显著性加重（P0.05），但是限流70%和80%没有显著性差异（P0.05）。（3）在由于门静脉限流造成腹腔器官瘀血方面：肠粘膜坏死主要发生于术后6h急性期内，限流80%以上则肠道损伤显著性加重，至术后第3天及以后，肠道粘膜逐渐恢复，不同限流比例所造成的差异逐渐趋于不明显。（4）在肝切除术后肝再生恢复方面，术后恢复时间是决定肝脏再生的最主要因素；限流80%同完全开放没有显著性差异，限流超过80%肝脏再生显著性下降，但是限流80%和90%没有显著性差异。结论：我们研发的新型定量化血流限制装置能够应用于肝切除手术中血流限制，但是在已产品化实例中，调节效率尚待提高。在完全阻断肝动脉血流的肝切除模型中，PV限流程度是影响生存的危险因素；PV限流80%，术中失血同完全阻断没有显著性差异。门静脉血流量同肝脏灌注压具有线性正相关，是影响生存的保护性因素：当血流限制80%时，则保护作用不具有显著意义；门静脉限流70%-80%区间内可能存在某一个IRI影响突然变化的阈值；门静脉限流80%-90%区间内可能存在某一个术后肝脏再生的阈值。
[Abstract]:Objective: to study the optimal proportion of blood flow limiting in hepatectomy, so as to reduce the hepatic function damage caused by blood flow restriction and the systemic adverse effects, and to reduce the complications of the operation. To improve survival and prognosis. Method 1: 1. According to the anatomical structure and blood flow characteristics of hepatic hilus, a quantitative hepatic portal blood flow limiting device was designed and developed, produced and used in animal experiments. 2. Quantitative hepatic portal blood flow limiter was used to study the effects of different flow limiting ratios on hepatic perfusion in rabbits. 3. A rabbit model of hepatectomy was established to block the hepatic artery. Zuo Ye and middle lobe hepatectomy were performed under different portal vein flow limiting ratios. The blood loss during the operation was counted. The changes of liver function and the 7 day survival rate at 6 hours and 3 days after hepatectomy were also studied in order to investigate the survival rate of 7 days after hepatectomy. Optimal flow limiting ratio of portal vein. Results: 1. Quantitative hepatic portal blood flow limiter has been approved by the State intellectual property Office, granted a utility model patent. 2. There was a linear positive correlation between portal vein blood flow and hepatic perfusion pressure in hepatic artery occlusion and portal vein limiting flow rabbit model. Linear regression equation: 1 absolute: P (Pu) = 85.825 2.051V (ml/min). 2%: P (Pu% = 0.296 0.662V (ml min-1%). The contribution ratio of hepatic venous blood flow to maintain hepatic perfusion pressure is about 29.6. 3. In the model of rabbit hepatectomy (Zuo Ye, middle lobe), the hepatic artery was completely blocked, the portal vein was controlled for 45 min: completely blocked, 90% and 80% were completely open and 70%. The 7-day survival rate was 0 ~ 1060,60,800.100. 4, respectively. In the model of rabbit hepatectomy (Zuo Ye, middle lobe), the hepatic artery was completely blocked and the portal vein was limited for 30 minutes. (1) there was no significant difference in blood loss between 80% and complete occlusion during the operation. (2) there was no significant difference in the amount of blood loss between the two groups. (2) there was no significant difference in the amount of blood loss between the two groups. According to the analysis of liver pathology and serum level of liver enzymes, no matter the proportion of liver cell injury was limited, the injury reached the peak at 6 h after operation, and then recovered gradually with the postoperative time. There was no significant difference between 70% and fully open current limit (P0.05). However, there was no significant difference between 70% and 80% of the limiting flow (P0.05). (3) in abdominal organ ecchymosis due to portal vein restriction: intestinal mucosal necrosis mainly occurred in the acute phase 6 hours after operation. More than 80% of the current limit increased significantly intestinal injury, and the intestinal mucosa gradually recovered on and after the third day after operation, and the differences caused by different flow limiting ratios tended to be insignificant. (4) the recovery of liver regeneration after hepatectomy; Postoperative recovery time was the most important factor in determining liver regeneration. There was no significant difference between 80% and 90% of the total opening, but there was no significant difference between 80% and 90%. Conclusion: the new quantitative blood flow limiting device developed by us can be applied to blood flow limitation in hepatectomy, but in the case of production, the regulation efficiency needs to be improved. In the hepatectomy model with complete occlusion of hepatic artery blood flow, the degree of PV flow limitation was the risk factor of survival, and the blood loss during operation was not significantly different from that of complete occlusion of PV flow limiting factor 80. Portal vein blood flow has a linear positive correlation with hepatic perfusion pressure and is a protective factor for survival: when the blood flow is limited to 80, the protective effect is not significant. There may be a threshold of sudden change of IRI in 70 ~ 80% of portal vein and a threshold of liver regeneration in 80 ~ 90% of portal vein.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R657.3

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