Dhar D K, Yamanoi A, Ohmori H, Nakashima Y, Yamamoto A, Osama N E, Kubota H, Kohno H, Nagasue N
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Hepatology. 1998 Sep;28(3):782-8. doi: 10.1002/hep.510280327.
ET receptor blocker (TAK-044) and NO donor (FK409) were used to improve the hepatic microcirculation following ischemia-reperfusion injury. In the first experiment (60 minutes of ischemia), 15 dogs were divided into three groups: group A (control), saline; group B, TAK 5 mg/kg; and group C, FK 0.4 mg/kg. In the second experiment (90 minutes of ischemia), 38 dogs were divided into six groups that underwent 90 minutes of hepatic ischemia followed by reperfusion: group I (control), saline only; group II, TAK 5 mg/kg and FK 3.2 mg/kg; group III, TAK 5 mg/kg and FK 0.4 mg/kg; group IV, TAK 5 mg/kg; group V, FK 0.4 mg/kg; and group VI, FK3.2 mg/kg. All drugs were administered through the portal vein. Following 60 minutes of ischemia, both FK and TAK produced significant improvement in hepatic microcirculation and enzymatic status when compared with the control group. After 90 minutes of ischemia, low doses of FK and TAK significantly improved hepatic microcirculation and reduced portal pressure following reperfusion in group III compared with group I. Leakage of hepatic enzymes was prevented and tissue injury score was significantly lower in group III. In group VI, early protection was obtained to some extent; however, blood pressure was reduced significantly following reperfusion compared with group I. In contrast, hepatocellular function deteriorated and the tissue injury score was higher in group II animals. TAK pretreatment with low doses of FK provided the best protection for the hepatic microcirculation in ischemia-reperfusion injury of the liver.
内皮素受体阻滞剂（TAK - 044）和一氧化氮供体（FK409）被用于改善缺血再灌注损伤后的肝微循环。在第一个实验（缺血60分钟）中，15只犬被分为三组：A组（对照组），给予生理盐水；B组，给予TAK 5毫克/千克；C组，给予FK 0.4毫克/千克。在第二个实验（缺血90分钟）中，38只犬被分为六组，进行90分钟肝缺血后再灌注：I组（对照组），仅给予生理盐水；II组，给予TAK 5毫克/千克和FK 3.2毫克/千克；III组，给予TAK 5毫克/千克和FK 0.4毫克/千克；IV组，给予TAK 5毫克/千克；V组，给予FK 0.4毫克/千克；VI组，给予FK3.2毫克/千克。所有药物均通过门静脉给药。缺血60分钟后，与对照组相比，FK和TAK均使肝微循环和酶学状态得到显著改善。缺血90分钟后，与I组相比，III组中低剂量的FK和TAK显著改善了肝微循环并降低了再灌注后的门静脉压力。III组预防了肝酶渗漏，且组织损伤评分显著更低。在VI组中，在一定程度上获得了早期保护；然而，与I组相比，再灌注后血压显著降低。相比之下，II组动物的肝细胞功能恶化，组织损伤评分更高。低剂量FK预处理TAK对肝脏缺血再灌注损伤的肝微循环提供了最佳保护。
