Poster Presentations

Session Title: CIRRHOSIS AND COMPLICATIONS - a)PATHOPHYSIOLOGY
Presentation Date: Apr 25, 2009

SORAFENIB DECREASES PORTAL PRESSURE, PORTOSYSTEMIC COLLATERAL BLOOD FLOW AND SPLANCHNIC BLOOD FLOW IN RATS WITH PREHEPATIC PORTAL HYPERTENSION

T. Reiberger, B. Angermayr, P. Schwabl, N. Rohr-Udilova, M. Peck-Radosavljevic
Gastroenterology & Hepatology, Medical University of Vienna, Vienna, Austria

Background: Angiogenesis plays a key role in development of portal hypertension (PHT) and represents a potential therapeutic target. We aimed to evaluate the effects of sorafenib, an multiple tyrosine kinase inhibitor on splanchnic hemodynamics in partial portal vein ligated (PPVL) rats.
Methods: 4 groups of rats were treated orally with sorafenib (Sora; 10mg/kg/day) or placebo (Plac) for 7 days, beginning at the day of PPVL/sham operation (SO), respectively: (1) PPVL-Sora, (2) PPVL-Plac, (3) SO-Sora and (4) SO-Plac. Measurements of mean arterial pressure (MAP), heart rate (HR), portal pressure (PP) and superior mesenterial artery blood flow (SMAF) were performed after 7 days of treatment. Porto-systemic collateral blood flow (PSCBF) was determined by radioactive microspheres. Splanchnic protein expression of CD31 (endothelial cell marker) were determined by western blotting.
Results: (Table1) PP and PSCBF were both significantly higher in PPVL than in SO rats. Treatment with Sora results in a significant decrease of PP and SMAF in PPVL-Sora compared to PPVL-Plac rats, while MAP remained unaffected. PPVL-Sora had markedly less PSCBF than PPVL-Plac rats. MAP and HR were similar in all groups. Expression of CD31 was significantly reduced in PPVL-Sora compared to PPVL-Plac rats.
Conclusion: Sorafenib reduces PP, SMAF and PSCBF in rats with prehepatic portal hypertension without cirrhosis and could represent an effective novel approach to treat PHT.