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Journal of Nippon Medical School

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Hemodynamic Features of Advanced Cirrhosis Due to Chronic Bile Duct Ligation

Yasumi Katsuta1, Xue-Jun Zhang1, Masaru Ohsuga1, Toshio Akimoto2, Hirokazu Komeichi1, Shuji Shimizu1, Toru Inami1, Akiko Miyamoto1, Katsuaki Satomura1 and Teruo Takano1

1First Department of Internal Medicine, Nippon Medical School
2Division of Laboratory Animal Science, Nippon Medical School


Aim: The aim of the present study was to compare the hemodynamic features of portal hypertension in rats with early cirrhosis with those of rats with advanced cirrhosis following common bile duct ligation (CBDL).
Methods: A total of 53 male Sprague-Dawley rats were used. Hemodynamics were evaluated under conscious and unrestrained conditions 4 weeks and 8 weeks after CBDL, and 4 weeks after a sham operation. Arterial pressure and portal pressure were measured directly via catheters placed in the right femoral artery and main portal vein, respectively. The cardiac index and organ (splanchninc organs, brain, kidneys and lungs) blood flow were determined by the reference sample method using 141Ce-labeled microspheres (15 μm in diameter). Arterial levels of endothelin-1 and nitrate/nitrite, as well as liver function variables, were also determined.
Results: Portal pressure was significantly higher 8 weeks after CBDL (15.8±2.1, n=8)than 4 weeks after CBDL (13.9±2.1 mmHg, n=12, p<0.05), and the hyperdynamic circulation of the early period was attenuated (p<0.05). Although hepatic artery blood flow 4 and 8 weeks after CBDL was higher than that after sham operation (p<0.05), portal territory blood flow was not increased. There was a significant positive correlation between portal pressure and portal territory blood flow 8 weeks after CBDL (r=0.822, n=8, p=0.012). In rats with anemia 4 weeks after CBDL, the hemoglobin concentration was negatively correlated with portal territory blood flow (r=-0.597, n=12, p=0.040).
Conclusion: Portal pressure was higher 8 weeks after CBDL than 4 weeks after CBDL and increased with portal territory blood flow, suggesting that portal hypertension is maintained by a mechanism consistent with the forward flow theory. Anemia might exacerbate the hyperdynamic systemic circulation 4 weeks after CBDL.

J Nippon Med Sch 2005; 72: 217-225

Keywords
forward flow theory, portal hypertension, anemia, endothelin-1, nitrate

Correspondence to
Yasumi Katsuta, MD, First Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
ykatsuta@nms.ac.jp

Received, April 6, 2005
Accepted, June 8, 2005