Katsuta Yasumi, Zhang Xue-Jun, Ohsuga Masaru, Akimoto Toshio, Komeichi Hirokazu, Shimizu Shuji, Inami Toru, Miyamoto Akiko, Satomura Katsuaki, Takano Teruo
First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
J Nippon Med Sch. 2005 Aug;72(4):217-25. doi: 10.1272/jnms.72.217.
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).
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 (141)Ce-labeled microspheres (15 mum in diameter). Arterial levels of endothelin-1 and nitrate/nitrite, as well as liver function variables, were also determined.
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).
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.
本研究旨在比较胆总管结扎(CBDL)后早期肝硬化大鼠与晚期肝硬化大鼠门静脉高压的血流动力学特征。
共使用53只雄性Sprague-Dawley大鼠。在CBDL后4周和8周以及假手术后4周,在清醒且不受约束的条件下评估血流动力学。分别通过置于右股动脉和门静脉主干的导管直接测量动脉压和门静脉压。使用(141)Ce标记的微球(直径15μm)通过参考样本法测定心脏指数和器官(内脏器官、脑、肾和肺)血流。还测定了内皮素-1和硝酸盐/亚硝酸盐的动脉水平以及肝功能变量。
CBDL后8周门静脉压(15.8±2.1,n = 8)显著高于CBDL后4周(13.9±2.1 mmHg,n = 12,p < 0.05),且早期的高动力循环减弱(p < 0.05)。尽管CBDL后4周和8周肝动脉血流高于假手术后(p < 0.05),但门静脉区域血流未增加。CBDL后8周门静脉压与门静脉区域血流之间存在显著正相关(r = 0.822,n = 8,p = 0.012)。在CBDL后4周贫血的大鼠中,血红蛋白浓度与门静脉区域血流呈负相关(r = -0.597,n = 12,p = 0.040)。
CBDL后8周门静脉压高于CBDL后4周,并随门静脉区域血流增加,表明门静脉高压由与前向血流理论一致的机制维持。贫血可能会加重CBDL后4周的高动力全身循环。