Development of the gene therapy against the organ dysfunction in the patients under LVAS support.

针对 LVAS 支持下患者器官功能障碍的基因疗法的开发。

• 批准号: 09557109
• 负责人: SAWA Yoshiki
• 金额: $ 8.64万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557109/
• 关键词: LVAS; liver dysfunction; microcirculation; LVAS; 術後肝障害

1. To forecast the hyper bilirubinemia in the patients after operation, we evaluated the preoperative factors (hepatocyte damage, hepatic sinusoid-endothelial dysfunction, liver function and inflammatory response). Operations performed were mitral valve replacement. We measured the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), hyaluronic acid (HA), total bilirubin (TB), choline estelase (ChE), interleukm-6 (IL-6), interleukin-8 (IL-8) and CRP before operation. We evaluated the correlation between these indexes and the peak level of TB in seven post-operative days. The levels of preoperative TB, ChE, I-IA and IL-6 had a good correlation with the peak level of postoperative TB.These results suggested that liver function, hepatic sinusoid-endothelial dysfunction and inflammatory reaction may play a significant role in forecast of postoperative hepatic failure in patients.2. To clarify the mechanism of hyper-bilirubinemia in the setting of left ventricular assis … More t device (LVAS), we evaluated the change of hepatocellular function, hepatic sinusoid-endothelial microcirculation and inflammatory response before and after LVAS implantation. We measured serum levels of total bilirubin (TB), transaminases (ALT,AST), interleukin (IL-6, IL-8), and HA ; a indicater for hepatic sinusoidal circulation, before and after LVAS implantation. The level of I-LA and IL-8, had a good correlation with the level of TB.However, the AST, ALT or 11-6 did not relate to the alternation of TB.These results suggested that hepatic sinusoid-endothelial dysfunction and inflammatory reaction may play a significant role in hepatic failure in patients following implantation of LVAS.3. Under the current situations we have increasing opportunities to manage the patients with posthepatitis and/or congestive liver dysfunction. In order to prevent postoperative hepatic failure we described perioperative management for those patients. We have no effective methods to estimate the functional reserve, but our data suggested that serum cholineesterase level at the preoperative states might demonstrate prognostic significance. Less

1.为了预测术后患者的高胆红素血症，我们评估了术前因素(肝细胞损伤、肝窦-内皮功能障碍、肝功能和炎症反应)。手术为二尖瓣置换术。测定血清天冬氨酸转氨酶(AST)、丙氨酸氨基转移酶(ALT)、透明质酸(HA)、总胆红素(TB)、胆碱酯酶(CHE)、白细胞介素6(IL-6)、白介素8(IL-8)和C反应蛋白(CRP)水平。我们评估了这些指标与术后7天结核病高峰水平之间的相关性。结论：1.术前TB、CHE、I-IA、IL-6水平与术后TB峰值有较好的相关性，提示肝功能、肝窦内皮细胞功能障碍和炎症反应对预测术后肝功能衰竭有重要意义。高胆红素血症在左室肥厚…发病机制中的作用观察移植前后肝细胞功能、肝窦内皮细胞微循环及炎症反应的变化。分别于术前、术后检测血清总胆红素(TB)、转氨酶(ALT、AST)、白介素6(IL-6)、白介素8(IL-8)和肝窦循环指标透明质酸(HA)。I-LA、IL-8水平与TB水平呈正相关，而AST、ALT、11-6水平与TB变化无关，提示肝窦-内皮功能障碍和炎症反应可能在LVAS术后肝功能衰竭中起重要作用。在目前的情况下，我们有越来越多的机会来处理肝炎后炎症和/或充血性肝功能障碍的患者。为了预防术后肝功能衰竭，我们描述了这些患者的围手术期处理。我们没有有效的方法来估计功能储备，但我们的数据表明，术前状态下的血清胆碱酯酶水平可能具有预后意义。较少

项目成果

澤 芳樹: "循環器疾患の遺伝子治療" 医学のあゆみ. 185-1. 91-94 (1998)

Yoshiki Sawa：“心血管疾病的基因治疗”医学史185-1（1998）。

Yoshiki Sawa: "Gene Therapy in Cardiovascular Surgery" Surgery Today. 28. 125-128 (1998)

Yoshiki Sawa：“心血管外科中的基因治疗”今日手术。

Takahiro Yamaguchi: "HEPATIC SINUSOID-ENDOTHELIAL DYSFUNCTION PLAYS A ROLE IN HYPERBILIRUBINEMIA IN PATIENTS FOLLOWIMNG IMPLANTATION OF LVAS" ASAIO JOURNAL. 43・5. 449-452 (1997)

Takahiro Yamaguchi：“肝窦内皮功能障碍在 LVAS 植入后患者的高胆红素血症中发挥作用”ASAIO 杂志 43・5（1997 年）。

Nobuaki Hirata, Hikaru Matuda: "Cardiovascular Surgery in The Patients With Liver Dysfunction" Journal of Japan Surgical society. 98(8). 671-675 (1998)

平田信明、松田光：“肝功能障碍患者的心血管手术”日本外科学会杂志。

Yoshiki Sawa: "Gene Therapy in Cardiovascular Surgery" Sugery Today. 28. 125-128 (1998)

Yoshiki Sawa：“心血管外科中的基因治疗”今日外科。