Z Gastroenterol 2011; 49 - P2
DOI: 10.1055/s-0031-1279839

Nebivolol deteriorates portal hemodynamics in cirrhotic rats by increasing splanchnic blood flow

T Reiberger 1, BA Payer 1, B Angermayr 1, V Fuhrmann 1, P Schwabl 1, B Jäger 1, T Hummel 1, T Horvatits 1, M Mitterhauser 1, M Peck-Radosavljevic 1
  • 1Dept. of Internal Medicine III, Div. of Gastroenterology & Hepatology, Medical University of Vienna, Austria

Introduction: Portal hypertension (P), as a function of Ohm's law (P=RxI) is influenced by intrahepatic resistance (R) and splanchnic blood flow (I). Non-selective beta-blockers (NSBB) decrease splanchnic blood flow and NO-donors (e.g. ISMN) decrease intrahepatic resistance, thus both drugs are used for treatment of portal hypertension. We evaluated the effects of Nebivolol, a third generation beta-blocker capable of increasing NO bioavailability on splanchnic and pulmonary hemodynamics in a cirrhotic rat model developing hepato-pulmonary syndrome (HPS).

Methods: Male Sprague Dawley rats underwent bile duct ligation (BDL) to induce cirrhosis.

The animals were orally treated with Nebivolol (NEBI; 10mg/kg) or vehicle (VEH) via feeding tube for seven days, starting three weeks after BDL, when cirrhosis was fully developed. 28 days after operation, heart rate (HR), mean arterial pressure (MAP), portal pressure (PP), and superior mesenteric artery blood flow (SMABF) were measured. Portosystemic collateral blood flow (PSCBF) and intrapulmonary shunting (IPS) were quantified by radioactive microsphere technique.

Results (Table-1): Body weight and MAP were similar in BDL-VEH and BDL-NEBI rats, whereas HR was signficantly reduced by Nebivolol treatment. (p<0.001). BDL-NEBI animals had significantly higher PP (p=0.005) and SMABF (p=0.016) than BDL-VEH animals. Nebivolol treatment did not affect IPS (p=0.996).

Conclusion: Nebivolol increases portal pressure in cirrhotic animals by increasing splanchnic blood flow without affecting pulmonary hemodynamics (IPS). Although no effects on PSCBF were observed, the safety of Nebivolol for treatment of cirrhotic patients with varices should be carefully evaluated.