Chromatographic pattern and biological activity of atrial natriuretic factor (ANF) in cirrhosis with ascites

Selected Abstracts from the Meeting of the Spanish Association for the Study of the Liver Madrid, Spain, June 1989

CHROMATOGRAPHIC PATTERN AND BIOLOGICAL ACTIVITY OF ATRIAL NATRIURETIC FACTOR (ANF) IN CIRRHOSIS WITH ASCITES W.Jim&ez, J.Gutkowska. P.Gi&. F.Rivera. V.Arroyo and J.Rcd& Hormonal Laboratory and Liver Unit, Hospital Clinic i Provincial. Barcelona. Spain and Clinical Research InstJtute of Montreal. Montreal, Quebec. Canada. Patients with cxrrhosis and asrites show sodium retention and increased plasma levels of ANF. a peptide with powerful natriuretic activity. To investigate whether this paradorlcal abservatlon could be related to a dysregulation in the synthetic process of ANF leading to abnormal molecular forms lacking biological activity, the chramatographic pattern of ANF contained in two plasma pools, one obtained from 57 patients with cirrhosis and ascltes and the other from 10 healthy subjects. were compared. ANF from the cirrhotic pool was also tested in a radioreceptor assay (RRA). which only detects the biological1 active form(s) of this peptide. ANF was extracted by Vycor glass powder, dissolved in 75 4: CH3CNIO.l % trifluor acetic acid, injected 1nt.oa HPLC system and eluted in tnfluor acetic acid (15-50 X. 1 mlfmin). RRA was performed by measurrng the competitive bIndIng of 125I-ANF to rat glomerular membranes in the presence of ANF isolated from cirrhotics or synthetic human o(ANF. The concentration of ANF in the plasma pool from cirrhotics MS about two-fold higher than that in the pool from controls (283 vs 133 fmol/ml). KPLC analysis of ANF showed an identical chromatographlc pattern in cirrhotlcs and controls. Three peaks of innwwreactive ANF. correspondJng to pro-ANF. a-ANF and ANF Arg 103-Tyr :i't,
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PROPR4NOLOL IN THE ,'ROPHVLAXISOF OESOPHAGEAL VARICEAL HAEMORRHAGE IN PATIENTS WITH CIRRHOSIS: A IlOUBLE-BLIND,MULTICENTER CONTROLLED TRIAL. J Bosch, RJ Groszmann. N Grace. M Navasa. HO Corm, J Rod&. Hospital Clime i Provincial, Barcelona; Yale University, New Haven, Faulkner Hospital, Boston. Hemorrhage from oesophageal varices (HOV) is one of the leading causes of death in cirrhosis. Prevention of HOV may thus improve the prognosis of these patients. Neither prophylactic portacaval shunts nor sclerotherapy have improved survival, although the former is successful in preventing bleeding. The present study evaluated the effectiveness of propranolol (Prop) in the prevention of the first HOV. This double-blind, randomized. tti.i was carried out in 3 centers. 102 cirrhotic patients (76% alcoholic) with endoscaplcally proven OV. hepatic vein pressure gradient (HVPG)), 12 rmnHg and no contraindication to Prop gave informed consent and were randomly asigned to Prop or placebo (Pla). To determine daily dose level, increasing doses of Prop (UP to 160 ng bid) were given while measuring HVPG until this fell by 25%. to<12 mmHg or heart rate fell below 55 bpm. Pla (w51) or Prop (n=51) were then administered at the dose level determined at catheterization. Endoscapy and HVPG were nerformed before, at 3 and 12 months and annually thereafter. Compliance was determined by pill counts (PC) and plasma Prop levels. Mean follow up was 16.3 months. 11 Pla patients (22%) bled from varices compared to 2 patients an Prop (4%) (p 12 mnHg; on the contrary, none of the 21 patients in whom HVPG decreased below 12 mmHg on the course of the study bled from varices (~9.05). The beneficial effect of Prop was greater in patients with big varices (size III-IV): g/25 Pla patients had vanceal haemorrhage YS O/27 Prop (~10.01). Deaths occurred in 1: pla compared to 8 Prop pts (NS). Therapy was withdrawn because of side effects in 12 pts. 4 F1": and 0 Prop (NS). Compliance (PC) was 75% for Pla and 80% for Prop. This study demonstrates that prophylact?c Prop reduced the risk of the initial hemorrhage from "arices. but d>d not decrease mortality significantly.