| Summary: | 碩士 === 國立陽明大學 === 傳統醫藥學研究所 === 89 === Portal hypertension is a major complication of liver cirrhosis. Cirrhosis and portal hypertension are associated with abnormalities in the cardiovascular system, with the development of a hyperkinetic circulatory state characterized by an increase in cardiac output, portal pressure, splanchnic blood flow and a decrease in arterial blood pressure and peripheral vascular resistance. Pharmacological therapy of portal hypertension aims to reduce portal blood inflow and/or intra-hepatic resistance. Long-Dan-Xie-Gan-Tang (LDXGT) is a commonly used traditional Chinese medicine in patients with chronic liver diseases in Taiwan. The hemodynamic effects of LDXGT in cirrhotic rats have not been explored. Although there are clinical reports showing portal hypotensive effects of carvedilol, a non-selectiveβ-adenoceptor antagonist withα1- adenoceptor antagonistic activity, the detailed hemodynamic effects in cirrhotic rats are also lacking. Propranolol, a β-adenoceptor antagonist, has been reported to reduce portal pressure in patients with cirrhosis, but the detailed hemodynamic effects in cirrhotic rats remain unclear. The present study was aimed to investigate the hemodynamic effects of LDXGT, carvedilol and propranolol administration in cirrhotic rats.
Portal hypertension with cirrhosis was induced by chronic bile duct ligation (CBDL) in Sprague-Dawley rats (230 ~ 250 g). Cirrhotic rats were allocated into separate groups: CBDL-Treatment group and CBDL-Vehicle group. Sham-operated rats served as controls. LDXGT and carvedilol was administered for 1-Week or 4-Week by gavage, starting at 3 weeks after ligation or at the time of ligation, respectively. Hemodynamic studies were performed by radioactive microsphere method after an overnight fast. We also investigate whether acute LDXGT i.v. infusion exerted a direct vasopressor effect by thermodilution method.
Our results showed that: (1) 1-Week carvedilol (5 mg/kg, bid, p.o.) administration partially ameliorated the hyperdynamic state of CBDL rats, including a significant decrease in heart rate, cardiac index, portal pressure, portal tributary blood flow and renal blood flow and an increase in systemic vascular resistance and renal vascular resistance. (2) 1-Week propranolol (15mg/kg, bid, p.o.) administration also partially ameliorated the hyperdynamic state of CBDL rats. (3) 1-Week LDXGTH (333 mg/kg, bid, p.o.) administration only caused a significant decrease in cardiac index and an increase in systemic vascular resistance. However, splanchnic hyperdynamic state did not changed after 1-Week LDXGTH administration. (4) 4-Week LDXGTH administration not only significantly ameliorated systemic hyperdynamic state but also caused a beneficial effect in splanchnic hyperdynamics, including a decrease in portal venous pressure and an increase in portal territory as well as renal vascular resistance. (5) 4-Week LDXGTL (111 mg/kg, bid, p.o.) administration exerted beneficial effects in both systemic and splanchnic hyperdynamic state. However, there was not a dose response relationship between 4-Week LDXGTL and LDXGTH administration. (6) Acute LDXGT i.v. infusion seems not to exert a vasopressor effect.
Our results suggested that 1-Week carvedilol, propranolol and 4-Week LDXGT treatment may provide beneficial effects in the management of portal hypertension and hyperdynamic circulation on cirrhotic rats.
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