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14 July 2020: Original Paper

Pretreatment with a Phosphodiesterase-3 Inhibitor, Milrinone, Reduces Hepatic Ischemia-Reperfusion Injury, Minimizing Pericentral Zone-Based Liver and Small Intestinal Injury in Rats

Shinichi Nakanuma 1ABCDEFG* , Hidehiro Tajima 1AC , Hiroyuki Takamura 1ACG , Seisho Sakai 1A , Ryosuke Gabata 1B , Mitsuyoshi Okazaki 1B , Hiroyuki Shinbashi 1B , Yoshinao Ohbatake 1B , Isamu Makino 1B , Hironori Hayashi 2A , Tomoharu Miyashita 1AC , Sachio Fushida 1A , Tetsuo Ohta 1ACE

DOI: 10.12659/AOT.922306

Ann Transplant 2020; 25:e922306

Figure 3 Histological changes of liver parenchyma related to hepatic ischemia-reperfusion (IR) injury: Representative hematoxylin and eosin staining sections of the sham, IR, and IR+milrinone groups (A). The livers of the IR group revealed histological changes characterized by hepatocellular vacuoles and focal necrosis (*), primarily in pericentral zone (zone 3) at low magnification. At high magnification, congestion, single cell necrosis of hepatocytes, and hepatocytes with vacuoles and swelling were observed around the central vein. Additionally, the sinusoidal structures were collapsed. In contrast, in the livers of the IR+milrinone group, focal necrosis of hepatocytes was markedly attenuated, and the lobular architecture was preserved. However, hepatocellular vacuoles were recognizable at zone 3 at low magnification. High magnification revealed the hepatocytes with vacuoles and swelling but little necrosis. The sinusoidal structure was almost maintained, and congestion was mild. PA – portal area; CV – central vein. Quantification of liver parenchyma injury with hepatic IR injury using Suzuki’s criteria at 5 h after reperfusion (B–E). The congestion score revealed that the zone 3 score in the IR group was significantly elevated as compared with that of the periportal zone (zone 1). The zone 3 score in the IR+milrinone group was significantly attenuated compared with that of the IR group (B). The hepatocyte vacuolization score revealed that the zone 3 score in the IR group was significantly higher than that of zone 1 (C). The necrosis scores revealed that the scores at zones 1 and 3 of the IR+milrinone group were significantly improved compared with those at the same zones in the IR group (D). The total scores revealed that the zone 3 score in the IR group was significantly higher than that of zone 1. The zones 1 and 3 scores of the IR+milrinone group were significantly attenuated as compared with those at the same zone in the IR group (E). * Significantly (P<0.01) different from zone 1 of the IR group. ** Significantly (P<0.001) different from zone 1 of the IR group. # Significantly (P<0.05) different from the IR group of the same zone. ## Significantly (P<0.01) different from the IR group of the same zone.

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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358