A978 AASLD ABSTRACTS

1081

COLLATERAL HEMODYNAMIC CHANGES DURING POST·PRANDIAL HYPEREMIA IN PORTAL HYPERTENSIVE RATS.Shin Sakurabayashi, Shampa Das, Roberto J. Groszmann, Yale UniversitylVAMC, West Haven, CT; Yale UniversityNA CT Healthcare System,New Haven, CT.

The aim of this study was to examine the effect of postprandial splanchnichyperemia on collateral blood flow and pressure in portal hypertensive rats(3 weeks; partial portal vein ligated rats). Pulsed-Doppler flowmeters wereimplanted around both the splenorenal shunt (SRS) (a large collateralvessel that develops in the portal hypertensive rat 3 or 4 days after theinduction of portal hypertension) and in the superior mesenteric artery(SMA, N==8). Changes in SRS and SMA flow were measured after astandard meal gavage in unanesthetized and unrestrained conditions. Per­cent change in SRS flow from baseline after gavage with a standard liquidmeal was significantly greater than that after gavage with an empty tube(peak, 27.1 ::!:2.9% vs. 9.4::!:2.0%; overall, 12.2::!:2.5% vs -4.4::!:2.1 %,respectively)(p$0.OO5). The percent increase in SRS flow after gavage wasnot significantly different than that in SMA flow. In order to study furtherthe significance of blood flow increase in the SRS collateral, in a separategroup of anesthetized rats (Ketamine 140 mglKg) we increased the bloodflow by progressively expanding the plasma volume with 3 different IVbolus of NIS ( 1 , 2 or 4 ml) The SRS blood flow increases was highlysignificant in each case (l6.9::!:1.0%, 27.l::!:4.7% and 65.8::!:4.8%). SRSpressure was measured in an additional group of portal hypertensiveanesthetized rats (N == 22) by introducing a 23gauge needle connected to apressure transducer into the SRS collateral. Bolus intravenous injection of1,2 or4 mL of saline induced an increased in SRS pressure of Il.9::!:2.1 %,12.5::!: 1.9% and 42.6::!:4.0%, respectively. These results demonstrate thatpostprandial splanchnic hyperemia and blood volume expansion increasescollateral blood flow and that collateral pressure rises with increases inflow. This finding indicates that a liquid meal of 4.5 ml in volume (0.443Cal/ml) increases blood flow and pressure significantly in the collateralcirculation.

1082CHRONIC HEMODYNAMIC EFFECTS OF A NEW LIVER SPE·CIFIC NO DONOR (V·PYRROINO) IN BILE DUCT LIGATED(BDL) RATS.Frederic Moal, Eric Vuillemin, Jua Wang, Nary Veal, Frederic Oberti, PaulCales, Hosp, Angers, France.

INTRODUCTION: NO is a major vasodilatator and could act as antifi­brotic factor. NO hepatic production is decreased in liver cirrhosis due todown-regulation of NOS activity. Thus,Hepatic vascular resistances(HVR) are increased and participe to portal hypertension (PHT). MoreoverNO participates to systemic vasodilatation. Liver specific NO donor, asV-PYRROINO, could decrease HVR without altering systemic hemody­namics. AIM: To assess the hemodynamic effects of V-PYRROINOchronic administration in BDL rats. METHODS: This study was performedin 37 male rats divided into 4 groups: Group 1: n ==7 sham rats with saline;group 2: n== 12 sham rats with V-PYRROINO (0,53 /Lmol.kg-1.h-1

) ; group3: n== II BDL rats with saline; group 4: n==7 BDL rats with V-PYRROINO(same dosage). Saline and V-PYRROINO were administred in femoralvein by osmotic pump during 24 days. Hemodynamic measurements ofmean arterial pressure (MAP), heart rate (HR), portal pressure (PP),spleno-renal shunt blood flow (SRS), and cardiac index (CI) were per­formed at 24 days in anesthetized rats. RESULTS: The hemodynamicresults are reported in the table. CONCLUSIONS: as expected, the sys­temic venous administration of V-PYRROINO -specific hepatic NO donor­improved PHT by decreasing PP (-24%) and venous collateral blood flow.However, this drug had systemic effects by decreasing significantly MAPwithout significant change in CI.

Hemodynamics changes ofV-PYRRO/NO administration inSDL rats

sham saline sham NO BOLsaline BOLNO p

Body weight (%) 26.4±12.7 220±9.2 12.4±11.8 15.1±13.8 0.06MAP (mmHg) 118.3±6.6 113.1±10.6 103.7±8.7'> 92.1±11.()&·c.d 0.0001HRlblmin) 441±24 428±45 409±30 418±30 NSPPlmmHg) 9.0±0.8 8.0±1.2 16.2±2.3_" 12.3±3.1_,·c.d 0.0001SRS (mllmin) o23±0.1 032±012 1.4±1.4_" 0.36±0.11' 0004CI(ml/mln 1100) 13.4±5.5 151±38 4O.5±9.3 " 35.6+5.4 c.c 00001

Significant differences between: a : Gr.3 vsGr 4;b: Gr.lvsGr.3; c:Gr.lvsGr.4; d : Gr.2 vsGr.4.

1083TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT(TIPS) FOR TREATMENT OF HEPATIC HYDROTHORAX:LONG-TERM RESULTS IN 40 PATIENTS.Volker Michael Siegerstetter, Andreas G. Ochs, Hubert E. Blum, Martin P.Rossie, Univ Hosp, Freiburg, Germany.

The aim of this study was to investigate the long-term effects of the TIPStreatment on patients with diuretic refractory hydrothorax, one of the mostsevere complication of portal hypertension. Fourty patients (Child-Pughclass A: 2, B: 26, C: 12 pts) with previous frequent pleurocenteses,

GASTROENTEROLOGY Vol. 118, No.4

permanent chest tubes, or unsuccessful attempts of pleurodesis were fol­lowed for 16::!:14 months (range:l day to 54 months)after TIPS implanta­tion. Results: TIPS placement reduced the portosystemic pressure gradientfrom 27::!:6 to 1O::!:5 mmHg. Eighteen patients (45%) required TIPSrevision after 7::!:9 months. Complete response was seen in 70.5%, partialresponse without need for further pleurocenteses in 11.7%, and lack ofresponse in 17.8%. In patients with response, the Child-Pugh score im­proved from 8.6::!: 1.8 to 6.7::!: 1.5, accompanied by an increase in serumalbumin concentration from 3.1::!:0.5 to 3.6::!:0.5 gIL. All 6 nonrespondersdied early (4::!:2 months), 5 from liver and I from renal failure. Eleven ofthe 34 responders (32%) died after 15::!: 10 months. Conclusions: TIPS iseffective in the treatment of refractory hydrothorax. Response to treatmentpredicts outcome.

1084DETECTION OF ENDOTHELIAL (ENOS) BUT NOT INDUCIBLE(INOS) NITRIC OXIDE SYNTHASE IN PREHEPATIC AND HE·PATIC PORTAL HYPERTENSIVE RATS.Michael M. Stumm, Maaike van der Kooij, Lazar T. Sumanovski, Pierre­Yves Martin, Juerg Reichen, Cornel C. Sieber, Univ Hosp Basel, Basel,Switzerland; Univ of Basel, Basel, Switzerland; Univ of Geneva, Geneva,Switzerland; Univ of Bern, Berne, Switzerland.

Introduction: Portal hypertension is accompanied by a nitric oxide (NO)dependent vasodilation, leading to a hyperdynamic circulation. Three iso­forms of NO producing synthases are characterized: nNOS, eNOS andiNOS. Whereas nNOS and eNOS are constitutively expressed, iNOS isonly detectable upon adequate induction. The source of increased NOlevels in chronic portal hypertension is yet unsettled. Aim: To determinethe expression of eNOS and iNOS in different organs of portal hyperten­sive as well as control rats. Methods: Sprague-Dawley rats were divided in6 groups: I) Partial portal vein ligated rats (PVL, n==4). 2) Bile duct ligatedrats (BDL, n==3). 3) Carbon tetrachloride treated rats (CCL4, n==3) 4)Sham operated rats (SH, n==4). Tissue asservation followed after 16 days(PVL, SH) or 21 days (BDL, CCL4), timepoints when the hyperdynamiccirculation in the respective animal models of portal hypertension is fullyestablished. 5) Control rats (N, no operation, n==4). 6) Positive control rats(treated with LPS, 20mglkg i.p., for 6h, n==2) for iNOS expression. Fromall organs, samples were taken and either paraffin embedded for immuno­histochemistry (!He) or snap frozen for immunoblotting (IB). The follow­ing organs were investigated: thymus, aorta thoracalis, heart, lung, esoph­agus, liver, spleen, kidney, pancreas, small and large intestine. IHC wascarried out on 2-5 /Lm tissue sections by applying either an antibodydirected to eNOS (rabbit anti-eNOS antibody, Santa Cruz Biotechnology)or iNOS (rabbit anti-iNOS antibody, J. Pfeilschifter). Tissue lysates wereinvestigated by IB for eNOS (rabbit anti-eNOS antibody, SCB) or iNOS(mouse anti-iNOS antibody, Transduction Laboratories). Results: IHCrevealed an evenly distributed eNOS expression in all 6 investigatedgroups. Expression of iNOS was restricted to macrophages in organs ofLPS treated and to the thymus of all investigated rats. In no other organ ofPVL, BDL, CCL4, SH and N rats iNOS was detectable. These findingswere further reflected by the same expression pattern in lB. Summary andconclusions: iNOS expression is not detectable neither by IHC, nor by IBin the inner organs of PVL, BDL, CCL4, SH and N, except for the thymus.This speaks against a role of iNOS in the maintainance of the hyperdy­namic circulatory state in chronic portal hypertension. We conclude that inthree models (prehepatic and hepatic) of chronic portal hypertension in therat, the main source for NO production depends on eNOS activity.

1085

L·ARGININE INFUSION PROTECTS AGAINST HYPERAM·MONEMIA ANDHEPATIC ENCEPHALOPATHY IN CIRRHOTICPATIENTS WITH VARICEAL HAEMORRHAGE.J-C Montet, L. Salmon, F. X. Caroli-Bosc, J. F. Demarquay, A. M. Montet,J. P. Delmont, INSERM, Marseille, France; Liver Dept, L' Archet II Hosp,Nice, France.

Hepatic encephalopathy (HE) is a serious complication of bleeding esoph­ageal varices and is believed to occur in about 20% of patients. The presentstudy was carried out in order to evaluate the effect of L-arginine infusionon the occurence of HE. Patients and methods: Thirty four cirrhoticpatients were enrolled in a randomized, placebo-controlled, clinical trial atthe time when they developed bleeding esophageal varices, without anyclinical sign of HE. In all patients, sclerotherapy and somatostatin wereused for the treatment of haemorrhage. L-arginine (25 g/day) was infusedintravenously over 4 hours for 7 consecutive days, in 16 of 34 patients. Theseverity of liver disease was assessed according to the Child-Pugh score(A: 14; B: 17; C: 3 patients). The neurological status (EEG, clinicalsymptoms) and blood ammonia levels were examined before starting thetreatment and 7 days after. Results: Arginine treatment significantly re­duced blood ammonia concentration by 40% (p=0.005), while the ammo­nia level was unchanged in the placebo group. The occurence of HE wassignificantly lower in the L-arginine treated patients (0/16) than in thecontrol patients (4/18) (p== 0.045, chi-square test). In addition, improve­ment in EEG profiles was two-fold more frequent in the treated group thanin the control group (p= 0.08) and conversely an aggravation was observedin 5 patients in the placebo group versus 0 in the arginine group (p==0.02).Conclusion: L-Arginine treatment strongly alleviates ammonemia levelsand appears to be effective in preventing HE.