Tsuchiya Yasuo, Suzuki Shohachi, Inaba Keisuke, Sakaguchi Takanori, Baba Satoshi, Miwa Mitsuharu, Konno Hiroyuki, Nakamura Satoshi
Second Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
J Surg Res. 2003 May 1;111(1):100-8. doi: 10.1016/s0022-4804(03)00078-7.
Endothelin (ET)-1 contributes to hepatic ischemia and reperfusion (HIR) injury in normal liver. This study was conducted to clarify the role of ET-1 in HIR injury in cirrhotic state.
Using thioacetamide-induced cirrhotic rats with spontaneous portosystemic shunt, we determined the changes in plasma aspartate aminotransferase (AST) levels, plasma and hepatic ET-1 values, 7-day survival rates, and hepatic oxygen saturation (SO(2)) by time-resolved spectroscopy as an indicator of hepatic microcirculation under intermittent or continuous total hepatic ischemia with subsequent partial hepatectomy.
Hepatic ET-1 levels in cirrhotic rats were significantly higher than those in noncirrhotic rats. Plasma and hepatic ET-1 levels at 1, 3 and 6 h of reperfusion after intermittent hepatic ischemia were significantly lower than those after continuous hepatic ischemia. In cirrhotic animals subjected to intermittent hepatic ischemia, the elevation of plasma AST levels at 1, 3 and 6 h of reperfusion and the decline in hepatic SO(2) at the end of 60-min hepatic ischemia and after reperfusion were significantly suppressed when compared with those subjected to continuous hepatic ischemia. Pretreatment with a nonselective endothelin receptor antagonist in continuous hepatic ischemia significantly ameliorated plasma AST levels and hepatic SO(2) values with less hepatic sinusoidal congestion, resulting in an improvement in the 7-day survival rate.
Continuous hepatic ischemia in the cirrhotic liver has disadvantages relating to microcirculatory derangement with more ET-1 production in partial hepatectomy. In liver surgery, pharmacological regulation of ET-1 production may lead to attenuation of reperfusion injuries for ischemically damaged cirrhotic liver.
内皮素（ET）-1在正常肝脏的肝缺血再灌注（HIR）损伤中起作用。本研究旨在阐明ET-1在肝硬化状态下HIR损伤中的作用。
使用硫代乙酰胺诱导的伴有自发性门体分流的肝硬化大鼠，我们通过时间分辨光谱法测定血浆天冬氨酸氨基转移酶（AST）水平、血浆和肝脏ET-1值、7天生存率以及肝脏氧饱和度（SO₂），以此作为间歇性或持续性全肝缺血并随后进行部分肝切除时肝脏微循环的指标。
肝硬化大鼠的肝脏ET-1水平显著高于非肝硬化大鼠。间歇性肝缺血再灌注后1、3和6小时的血浆和肝脏ET-1水平显著低于持续性肝缺血后。与持续性肝缺血的肝硬化动物相比，间歇性肝缺血的肝硬化动物在再灌注1、3和6小时时血浆AST水平的升高以及在60分钟肝缺血结束时和再灌注后肝脏SO₂的下降均得到显著抑制。在持续性肝缺血中用非选择性内皮素受体拮抗剂预处理可显著改善血浆AST水平和肝脏SO₂值，肝窦充血减轻，从而提高7天生存率。
肝硬化肝脏的持续性肝缺血在部分肝切除时与微循环紊乱及更多ET-1产生有关，存在不利之处。在肝脏手术中，对ET-1产生进行药理调节可能会减轻缺血性损伤的肝硬化肝脏的再灌注损伤。
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