• Makoto Kume, Ramin Banafsche, Yuzo Yamamoto, Yoshio Yamaoka, Rainer Nobiling, Martha-Maria Gebhard, and Ernst Klar.
• Department of General Surgery, University of Heidelberg, Heidelberg, Germany. kumacmd-gi@umin.ac.jp
• J. Surg. Res. 2006 Dec 1;136(2):209-18.

BackgroundPhosphodiesterase-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 MethodsMale 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.ResultsIn 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.ConclusionThe 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.

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