| Summary: | 碩士 === 國立陽明大學 === 傳統醫藥學研究所 === 87 === The hyperdynamic circulation of portal hypertension is characterized by decrease in arterial blood pressure and vascular resistance and increase in portal venous pressure and splanchnic blood flow. It has been reported that the portal pressure gradient is an important risk factor for oesophageal variceal hemorrhage, a major complication of portal hypertension. The pharmacological treatment of portal hypertension aims to treat acute bleeding episodes or prevent variceal bleeding. Synephrine (SYN) is a major pressor principles of Fructus Aurantii (the unripe fruits of Citrus aurantium L.). Octreotide (OCT) is a synthetic 8-amino-acid analogue of somatostatin with prolonged action. The purpose of this study was to investigate the effects of chronic SYN and OCT administration on portal hypertensive rats.
Portal hypertension without cirrhosis was induced by partial portal vein ligation (PVL) in Sprague-Dawley rats (230-260 g). Sham-operated (Sham) rats served as controls. There were three study groups: PVL-SYN group, PVL-Vehicle group, and Sham-Vehicle group. SYN (1 mg/kg/12hr, p.o.) or Vehicle (0.1N HCl, p.o.) was administered on the day of ligation and continued thereafter for another 7 days on PVL rats. On the 9th day, hemodynamic parameters were measured after an overnight fast, using radioactive microsphere method.
Portal hypertension with cirrhosis was induced by chronic bile duct ligation (CBDL) in Sprague-Dawley rats (250-300 g). Sham-operated (Sham) rats served as controls. There were three study groups: CBDL-SYN group, CBDL-Vehicle group, and Sham-Vehicle group. SYN (1 mg/kg/12hr, p.o.) or Vehicle (0.1N HCl, p.o.) was administered on the 21st day after surgery (when hyperdynamic state has been developed), and continued thereafter for another 6 days on CBDL rats. On the 8th day, hemodynamic parameters were measured after an overnight fast, using radioactive microsphere method.
Portal hypertension with cirrhosis was induced by chronic bile duct ligation (CBDL) in Sprague-Dawley rats (250-300 g). Sham-operated (Sham) rats served as controls. There were two study groups: CBDL-OCT group and CBDL-Vehicle group. OCT (30 mg/kg/12hr, s.c.) or Vehicle (saline, 12h-1, s.c.) was administered on the day of three weeks after surgery (when hyperdynamic state has been developed), and continued thereafter for another 6 days on CBDL rats. On the 8th day, hemodynamic parameters were measured after an overnight fast, using radioactive microsphere method.
SYN significantly ameliorated the hyperdynamic state of PVL rats, including reduction 13.5% of portal venous pressure, 20.0% of portal tributary blood flow and 12.1% of cardiac index; elevation 11.2% of mean arterial pressure, 26.0% of systemic vascular resistance, and 47.2% of portal territory vascular resistance. Hepato-collateral vascular resistance was not changed by SYN. Despite such improvement, PVL-SYN still exhibited hyperdynamic state as compared to sham rats.
SYN significantly ameliorated the hyperdynamic state of CBDL rats, including reduction 10.1% of portal venous pressure, 20.4% of portal tributary blood flow and 18.8% of cardiac index; elevation 22.7% of mean arterial pressure, 50.9% of systemic vascular resistance, and 67.8% of portal territory vascular resistance. Hepato-collateral vascular resistance was not changed by SYN. Despite such improvement, CBDL-SYN still exhibited hyperdynamic state as compared to sham rats.
OCT treatment induced reduction of cardiac index, and increased systemic vascular resistance. However, portal venous pressure, portal tributary blood flow, mean arterial pressure, portal territory vascular resistance, and hepato-collateral vascular resistance was not changed by OCT.
Our results showed that synephrine treatment significantly ameliorated the hyperdynamic state of portal hypertensive rats, with reduction of portal venous pressure and portal tributary blood flow and elevation of mean arterial pressure in portal hypertensive rats with or without cirrhosis. Our results also showed that 7-day administration of octreotide only led to partial improvement of cardiac index and systemic vascular resistance in cirrhotic rats.
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