Volume 8, Issue 1, Pages 29-34 (August 2001) Combined use of adenosine and amrinone inhibits reperfusion injury of rat liver  Kunihiro Katsuragi, Shigekazu Takemura, Yukiko Minamiyama, Hiromu Tanaka, Kazuhiro Hirohashi, Masayasu Inoue, Hiroaki Kinoshita  Pathophysiology  Volume 8, Issue 1, Pages 29-34 (August 2001) DOI: 10.1016/S0928-4680(01)00062-1

Fig. 1 Effect of adenosine and amrinone on the mean arterial blood pressure (MBP) after reperfusion. Under urethane anesthesia, hepatic artery and the branches of the portal vein supplying the lateral, medial left and medial right lobes were occluded for 45 min. At the time of reperfusion, varying doses of adenosine (1, 5, or 10 μmol/kg per min) or amrinone (0.05 or 0.1 μmol/kg per min) were infused through the portal vein over a period of 60 min. Adenosine (1 μmol/kg per min) and amrinone (0.05 μmol/kg per min) were also infused simultaneously. Sham operated and the control groups were administered with the same volume of saline (3 ml/h). The results are expressed as the mean±S.E.M. during from 5 to 7 animals. * P<0.05 as compared with control rats. Pathophysiology 2001 8, 29-34DOI: (10.1016/S0928-4680(01)00062-1)

Fig. 2 Effect of adenosine and amrinone on plasma levels of alanine aminotransferase levels after reperfusion. Animals were treated as described in Fig. 1. At 60 min after reperfusion, plasma samples were collected as described in the text. The results are expressed as the mean±S.E.M. during from 5 to 7 animals. * P<0.05 as compared with control rats. Pathophysiology 2001 8, 29-34DOI: (10.1016/S0928-4680(01)00062-1)

Fig. 3 Effect of adenosine and amrinone on cAMP levels in the reperfused liver. Animals were treated as described in Fig. 1 except for the fixed dose of adenosine (1 μmol/kg per min) and amrinone (0.05 μmol/kg per min). The results are expressed as the mean±S.E.M. during from 5 to 7 animals. ** P<0.01 as compared with control rats. Pathophysiology 2001 8, 29-34DOI: (10.1016/S0928-4680(01)00062-1)

Fig. 4 Effect of adenosine and amrinone on cGMP levels in the reperfused liver. Animals were treated as described in Fig. 3. The results are expressed as the mean±S.E.M. during from 5 to 7 animals. ** P<0.01 as compared with control rats. Pathophysiology 2001 8, 29-34DOI: (10.1016/S0928-4680(01)00062-1)

Fig. 5 Effect of adenosine and amrinone on plasma levels of nitrite plus nitrate. Animals were treated as described in Fig. 3. The results are expressed as the mean±S.E.M. during from 5 to 7 animals. ** P<0.01 as compared with control rats. Pathophysiology 2001 8, 29-34DOI: (10.1016/S0928-4680(01)00062-1)

Fig. 6 Histology of the liver at 1 h after reperfusion. Animals were treated as described in Fig. 3. Excised liver tissues were fixed with 10% buffered formalin and embedded in paraffin. Sections were stained with hematoxylin and eosin. In control group (A and E), extensive necrosis of centrilobular cells and ballooning of hepatocytes are apparent. In the 1 μmol/kg per min of adenosine (B and F) or 0.05 μmol/kg per min of amrinone (C and G) groups, hepatic parenchymal necrosis was improved. With the combination of adenosine and amrinone group (D and H), hepatocytes were well preserved. The original magnification of pannels (A, B, C and D) was X50, and E, F, G, and H was X100. Pathophysiology 2001 8, 29-34DOI: (10.1016/S0928-4680(01)00062-1)