14 July 2020 : Original article
Pretreatment with a Phosphodiesterase-3 Inhibitor, Milrinone, Reduces Hepatic Ischemia-Reperfusion Injury, Minimizing Pericentral Zone-Based Liver and Small Intestinal Injury in Rats
Shinichi Nakanuma1ABCDEFG*, Hidehiro Tajima1AC, Hiroyuki Takamura1ACG, Seisho Sakai1A, Ryosuke Gabata1B, Mitsuyoshi Okazaki1B, Hiroyuki Shinbashi1B, Yoshinao Ohbatake1B, Isamu Makino1B, Hironori Hayashi2A, Tomoharu Miyashita1AC, Sachio Fushida1A, Tetsuo Ohta1ACEDOI: 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.