Dynamic changes of post-ischemic hepatic microcirculation improved by a pre-treatment of phosphodiesterase-3 inhibitor, milrinone
Dynamic changes of post-ischemic hepatic microcirculation improved by a pre-treatment of phosphodiesterase-3 inhibitor, milrinone
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DOI：
10.1016/j.jss.2006.05.038
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发表时间：
2006-12-01
影响因子：
2.2
通讯作者：
Klar, Ernst
中科院分区：
文献类型：
--
作者：
Kume, Makoto;Banafsche, Ramin;Klar, Ernst
背景资料。已有研究表明，抑制磷酸二酯酶-3可以减轻肝脏热缺血再灌注损伤。本研究旨在通过活体显微镜观察磷酸二酯酶-3抑制剂米力农对大鼠肝脏缺血后微循环的影响。雄性Wistar大鼠随机分为3组：A组，米力农预处理组；B组，缺血预适应组；C组，不预处理组。所有动物都接受了左肝外侧叶60分钟的热缺血。活体视频显微镜观察微血管灌流和白细胞-内皮细胞相互作用。肝细胞存活率和细胞损伤分别通过三磷酸腺苷组织浓度以及丙氨酸氨基转移酶和乳酸脱氢酶血液水平来量化。A、B组大鼠肝组织环磷酸腺苷浓度明显升高。再灌流后，大鼠肝窦内微血管灌流明显维持，肝窦内和肝窦后小静脉内贴壁白细胞数量减少。与对照组相比，两组患者的血清转氨酶水平均明显降低。肝脏微循环的改善肯定源于米力农对肝脏缺血再灌流的细胞保护作用。这一效应是通过改善能量状态和减少肝脏酶的释放来概括的，并模拟了缺血预适应的效果。(C)2006 Elsevier Inc.保留所有权利。
Background. Phosphodiesterase-3 inhibition has been shown to attenuate hepatic warm ischemia-reperfusion injury. The aim of this study was to investigate the effect of milrinone, phosphodiesterase-3 inhibitor, on post-ischemic microcirculation of rat livers by intravital microscopy.Materials and methods. Male Wistar rats were randomly assigned to three groups; group A, milrinone pre-treatment; group B, ischemic pre-conditioning; and group C, no pre-treatment. All animals underwent a 60-min warm ischemia of the left lateral liver lobe. Microvascular perfusion and leukocyte-endothelial interaction were observed by intravital videomicroscopy. Hepatocellular viability and cellular damage were quantified by adenosine triphosphate tissue concentration as well as alanine aminotransferase and lactate dehydrogenase blood levels, respectively.Results. In groups A and B, cyclic AMP hepatic tissue concentration was elevated significantly. After reperfusion, microvascular perfusion in hepatic sinusoids was significantly better maintained, and the number of adherent leukocytes was reduced in sinusoids and in post-sinusoidal venules in these rats. Serum transaminase blood levels were suppressed significantly in these groups compared with controls.Conclusion. The demonstrated improvement of hepatic microcirculation is certainly derived from milrinone induced cell protection in ischemia reperfusion of the liver. This effect is outlined by improved energy status and reduced liver enzyme liberation and mimics the effect of ischemic pre-conditioning. (c) 2006 Elsevier Inc. All rights reserved.