89 EFFECTS OF SOMATOSTATIN ON SPLANCHNIC HEMODYNAMICS AND PLASMA GLUCAGON LEVELS IN PORTAL HYPERTENSIVE RATS D, Kravetz, J.Bosch, M.Arderiu, P. Pizcueta, R, Casamitjana, J.Chesta, F.Rivera, J,Rod~s, Liver Unit, Hospital Cl~nic i Provincial , Universi ty of Barcelona.

I t has been suggested that increased glucagon (GL) levels play an important role in the hyperdynamic c i rcu la t ion associated with portal hypertension. The present study was aimed at invest igat ing the effects of somatostatin (SMT), a potent i nh ib i t o r of GL secretion, on the splanchnic and systemic hemodynamics and plasma GL in rats with portal hypertension induced by par t ia l portal vein l i ga t ion (PVL, n=26) and sham operated controls (Sham, n=18) recei- ving SMT (20 ug/Kg/h af ter a bolus of 15 ug, PVL n=13, Sham n=9) or placebo ( ident ica l sal ine infusion, PVL n=13, Sham n= 9). After 30 min of SMT or placebo infusion portal (PP) and a r te r i a l pressures were measured and cardiac output and regional blood flows were determined using radioact ive microspheres, PVL rats had s ign i f i can t l y higher PP (13,6+0.6 vs 6.4+0.4 mmHg, p<O. O01) and portal venous inf low (PVl) (7,5+0.6 vs 4.5+0.2 ml/min TOO g, p<O~O01) than sham control rats. SMT infusion in PVL rats sTgni f icant ly reduced PP (~14%, p<O.05) and PVI (-29%, p<O. Ol), but increased portal venous resistance (PVR) by 35% (p(O.05). Plasma GL was markedly reduced by SMT (from 332+51 to 175+10 pg/ml, p<O. O05) to levels s imi lar to those observed in sham control animals (T76±22 pg/ml, NS). In this la ter group, SMT infusion caused s ign i f i can t a lbe i t lesser reductions in PVI (18%)(p<0,02) and GL (29%)(p<0,05). PP did not decrease (6.4+0.4 vs 7.1+0,4 mmHg, NS) because of a marked increase in PVR (33%, p<O.Ol), that re f lects a venoconstrictor ef fect . SMT had no ef fect on a r te r i a l pressure or cardiac output in PVL or sham rats, Our results show that normalization of plasma GL by SMT p a r t i a l l y reverses the increased PP and PVI of portal hypertensive rats. This, together with the lower effects of SMT in control animals, support a physiopathologi- cal role of GL in portal hypertension.

70 THE EXTENT OF PORTAL SYSTEMIC SHUNTING MODIFY THE RESPONSE OF PORTAL PRESSURE TO BLOOD VOLUME RESTITUTION FOLLOWING A HAEMORRHAGE IN CIRRHOTIC RATS D. Kravetz, J, Bosch, M, Arderiu, P. Pizcueta, J. Rod~s. Liver Unit, Hospital Cl~nic i Provincial . University of Barcelona,

I t has been shown that in rats with prehepatlc portal hypertension, blood volume res t i t u t i on fo l lowing a haemorrhage produce an increase of portal pressure (PP) beyond control values because of an increase in portal venous resistance (PVR). The present study investigated whether th is phenomenon is also observed in rats with c l r rhosis of the l i ve r induced by C14C, a model which is probably closer to the c l i n i ca l s i tuat ion. Since C14C induced-clrrhosis causes mild portal systemic shunting (PSS), in part of the c i r rho t i c rats (12 out of 36) PSS was enhanced by a t ransient (4-days) par t ia l constr ic t ion of the portal vein, that was removed one week pr ior to the study, After baseline measurements of PP and a r te r ia l pressure, blood was withdrawn (15 ml/Kg) and reinfused 15 min la ter , After blood reinfusion, PP and a r te r i a l pressure were measured again and cardiac output, regional blood flows and PSS were determined using radioact ive microspheres . PSS was of 78+11% in the c i r rho t i c rats that had temporary portal vein constr ic t ion, but only 5+2 %, (p(O.O01) in those who had not. Blood volume res t i t u t i on in low PSS rats did not produce any s ign i f i can t modif icat ion in splanchnic or systemic haemodynamics. However, in rats with high PSS, blood volume res t i t u t i on produced a s ign i f i can t increase in PP (from 9,9+0.9 to 13.5+0,9 mmHg, p(O.02). This increase in PP af ter blood reinfusion was due to a s ign i f i can t increase in PVR (from 1.3+0.2 to 1.9+0,2 mmHg/ml/min I00 g, I)(0,05), since no s ign i f i can t change was observed Tn portal bTood flow (8.4+1.5 vs 7,5+ 0,4 ml/min I00 g, NS) or systemic haemodynamlcs, Our results show that blood volume res t i t u t i on a f ter a haemorrhage worsens the portal hypertension syndrome in c i r rho t i c rats with high PSS but not in those with low PSS, thus demonstrating that the extent of PSS is an important mediator of th is deletereous ef fect ,

$37