Relation of cirrhotic ascites to α-human atrial natriuretic peptide

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51 PLASMA ENDOTOXlN CONCENTRATIONIN CHRONIC ALCOHOLICS H. Fukui, J.Ch. Bode, Ch. Bode Division of Gastroenterology, Department of Internal Medicine, Robert-Bosch-Krankenhaus, Stuttgart, F.R.G. Despite numerous studies on the incidence of endotoxemia in patients with chronic liver disease quantitative analysis has not yet been performed. We have measured plasma endotoxin (Et) concentration in chronic alcoholics and non-alcoholic cirrhotics by the chromogenic assay. Methods: A total of 63 chronic alcoholics (CA), 9 patients with non-alcoholic liver~is (NALC) and 8 normal subjects were studied. On the basis of histological and clinical findings 50 alcoholics were classified to have liver cirrhosis (ALC), 6 to have fatty liver (FL) and 7 to have alcoholic hepatitis (AH). Plasma Et was measured by the chromogenic substrate assay (KabiVitrum)(Friberger Pet al: Progr Clin Biol Res 93: 195, 1982). Four concentrations of Et were added to each plasma as reference standards (125, 250, 375 and 500 pg/ml plasma) before the heating. Results: The plasma Et levels in CA were significantly higher than in controls (25.9,.2.2 v ~ O pg/ml, mean~SEM, p<O.O01). Plasma Et in ALC, AH and FL were 26.6±3.0, 29.7~9.1 and 18.6~3.8 pg/ml, respectively. Plasma Et levels in ALC were significantly higher than that in NALC (17.3±3.3 pg,ixO.025). In ALC with and without ascites Et levels were 26.7~3.9 and 26.5~4.6 pg/ml, respectively. Patients with hypoalbuminemia (~3.5 g/dl) had higher Et levels than those with serum albumin over 4.0 g/dl (32.2±4.6 vs 16.7±3.4 pg/ml, p<O.02). Et levels were neither correlated to the grade of esophageal varices nor splenomegaly. In most alcohoiics including LC with ascites, Et levels over 50 pg/mI were noted only within the first 72 hrs of admission and Et rapidly decreased with total abstinence. Conclusions: The higher plasma concentrations of Et in ALC compared to NALC and the distinct increase of Et concentration in early stages of ALD during and shortly after alcohol excess suggest that Et might be of importance for the development of alcoholic liver injury. 52 RELATION OF CIRRHOTIC ASCITES TO ~-HUMAN ATRIAL NATRIURETIC PEPTIDE H. Fukui. T. TsuJii. M. Matsumura. S. Okamoto. M. Uemura. J. Yamao. M. Matsumoto, Ch. Bode*, J. Ch. Bode~, 3rd Department of Internal Medicine, Nara Medical University, Kashihara, Japan and *Department of Internal Medicine, Robert-Bosch-Krankenhaus, Stuttgart, F.R.G. Patzents with ixver cirrhosis(LC) frequently display progressive zmpairement of renal sodzum(Na) and water handllng, leadlng to the formatlon of ascites. Among several hormonal and neural factors, the absence of a putative natriuretzc factor has been postulated as a cause for renal Na retention. The alm of this study was to explore the relationships of renal Na handllng and ascztes formation to plasma immunoreactlve H-human atrial natriuretlc polipeptzde(Ir-~-hANP) zn clrrhotlcs. Methods:After equilibration on a 120-mEq Na diet, plasma Ir-~-hANP, renin actlvityiPRA) and noreplnephrine(NE) were measureo in 21 cirrhotics. Clrrhotlcs with ascites were then placed on a 35-mEq Na diet and, if necessary, given spiro- nolactone(iOOmg/day). Identical examinations were again performed when ascites just dis- appeared. Plasma Ir-~-hANP was measured by the RIA descrzbed by Naruse et al(Naruse el al: Peptzdes 7:141,1986). PRA and NE were measured by RIA and HPLC, respectlvely. Results:Ir-~ -hANP in cirrhotics was greater than In normal sub3ects(382~288 vs 177,68pg/ml,p<O.05). In LC wxthout ascztes, Ir-~-hANP was positively correlated with creatinine clearance(Ccr) and urinary Na excretlon. Cirrhotlcs wzth ascites and low Ccr excreted little Na in spite of hzgh Ir-~-hANP levels. On the basis of the ir-~-hANP levels before and after the treatment of ascltes, cirrhotlcs wxth ascxtes were subdzvided into 2 groups. In the group I Ir-~-hANP was lowered from hlgh basal values and in the group II zt was elevated from normal basal values. PRA and NE were elevated in the group I and lowered in the group II. Ccr in the group I was lower than that zn the group II throughout the study. Conclus~o~s:Ir-~-hANP was closely related to Ccr and urinary Na excretzon in LC without ascites. In LC with ascites and impaired renal circulation these relations were deranged. The difference in renal func- tion and plasma volume may account for the dzfference in the 2 groups of LC wlth ascites. $28

Transcript of Relation of cirrhotic ascites to α-human atrial natriuretic peptide

51 PLASMA ENDOTOXlN CONCENTRATION IN CHRONIC ALCOHOLICS

H. Fukui, J.Ch. Bode, Ch. Bode Div is ion of Gastroenterology, Department of Internal Medicine, Robert-Bosch-Krankenhaus, Stu t tgar t , F.R.G.

Despite numerous studies on the incidence of endotoxemia in pat ients with chronic l i v e r disease quant i ta t ive analysis has not yet been performed. We have measured plasma endotoxin (Et) concentration in chronic a lcohol ics and non-alcohol ic c i r r ho t i c s by the chromogenic assay. Methods: A to ta l of 63 chronic a lcohol ics (CA), 9 pat ients with non-alcohol ic l i v e r ~ i s (NALC) and 8 normal subjects were studied. On the basis of h is to log ica l and c l i n i c a l f ind ings 50 alcohol ics were c lass i f i ed to have l i v e r c i r rhos is (ALC), 6 to have f a t t y l i v e r (FL) and 7 to have a lcohol ic hepat i t i s (AH). Plasma Et was measured by the chromogenic substrate assay (KabiVitrum)(Friberger P e t a l : Progr Cl in Biol Res 93: 195, 1982). Four concentrations of Et were added to each plasma as reference standards (125, 250, 375 and 500 pg/ml plasma) before the heating. Results: The plasma Et levels in CA were s i g n i f i c a n t l y higher than in controls (25.9,.2.2 v ~ O pg/ml, mean~SEM, p<O.O01). Plasma Et in ALC, AH and FL were 26.6±3.0, 29.7~9.1 and 18.6~3.8 pg/ml, respect ive ly . Plasma Et levels in ALC were s i g n i f i c a n t l y higher than that in NALC (17.3±3.3 pg,ixO.025). In ALC with and without ascites Et levels were 26.7~3.9 and 26.5~4.6 pg/ml, respect ively. Patients with hypoalbuminemia (~3.5 g /d l ) had higher Et levels than those with serum albumin over 4.0 g/dl (32.2±4.6 vs 16.7±3.4 pg/ml, p<O.02). Et levels were nei ther correlated to the grade of esophageal varices nor splenomegaly. In most a lcohoi ics including LC with ascites, Et levels over 50 pg/mI were noted only w i th in the f i r s t 72 hrs of admission and Et rap id ly decreased with to ta l abstinence. Conclusions: The higher plasma concentrations of Et in ALC compared to NALC and the d i s t i n c t increase of Et concentration in ear ly stages of ALD during and shor t ly a f te r alcohol excess suggest that Et might be of importance for the development of a lcohol ic l i v e r in ju ry .

52 RELATION OF CIRRHOTIC ASCITES TO ~-HUMAN ATRIAL NATRIURETIC PEPTIDE

H. F u k u i . T. T s u J i i . M. M a t sumura . S. Okamoto. M. Uemura. J . Yamao. M. Matsumoto, Ch. Bode*, J. Ch. Bode~, 3rd Department of Internal Medicine, Nara Medical University, Kashihara, Japan and *Department of Internal Medicine, Robert-Bosch-Krankenhaus, Stuttgart, F.R.G.

Patzents with ixver cirrhosis(LC) frequently display progressive zmpairement of renal sodzum(Na) and water handllng, leadlng to the formatlon of ascites. Among several hormonal and neural factors, the absence of a putative natriuretzc factor has been postulated as a cause for renal Na retention. The alm of this study was to explore the relationships of renal Na handllng and ascztes formation to plasma immunoreactlve H-human atrial natriuretlc polipeptzde(Ir-~-hANP) zn clrrhotlcs. Methods:After equilibration on a 120-mEq Na diet, plasma Ir-~-hANP, renin actlvityiPRA) and noreplnephrine(NE) were measureo in 21 cirrhotics. Clrrhotlcs with ascites were then placed on a 35-mEq Na diet and, if necessary, given spiro- nolactone(iOOmg/day). Identical examinations were again performed when ascites just dis- appeared. Plasma Ir-~-hANP was measured by the RIA descrzbed by Naruse et al(Naruse el al: Peptzdes 7:141,1986). PRA and NE were measured by RIA and HPLC, respectlvely. Results:Ir-~ -hANP in cirrhotics was greater than In normal sub3ects(382~288 vs 177,68pg/ml,p<O.05). In LC wxthout ascztes, Ir-~-hANP was positively correlated with creatinine clearance(Ccr) and urinary Na excretlon. Cirrhotlcs wzth ascites and low Ccr excreted little Na in spite of hzgh Ir-~-hANP levels. On the basis of the ir-~-hANP levels before and after the treatment of ascltes, cirrhotlcs wxth ascxtes were subdzvided into 2 groups. In the group I Ir-~-hANP was lowered from hlgh basal values and in the group II zt was elevated from normal basal values. PRA and NE were elevated in the group I and lowered in the group II. Ccr in the group I was lower than that zn the group II throughout the study. Conclus~o~s:Ir-~-hANP was closely related to Ccr and urinary Na excretzon in LC without ascites. In LC with ascites and impaired renal circulation these relations were deranged. The difference in renal func- tion and plasma volume may account for the dzfference in the 2 groups of LC wlth ascites.

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