Bendtsen, Flemming

Gerbes, Alexander L.

Henriksen, Jens H.

English

Open Access LMU

LETTERS TO THE EDITOR 419 4 Burman P, Karlsson FA, Oberg K, Aim G. Autoimmune thyroid disease in interferon-treated patients. Lancet 1985; ii: 100-1. 5 Mayet W J, Hess G, Gerken G, et al. Treatment of chronic type B hepatitis with recombinant or-interferon induces autoantibodies not specific for chronic hepatitis. Hepatology 1989; 10: 24-8. 6 Renault PF, Hoofnagle JH. Side effects of alpha interferon. Semin Liver Dis 1989; 9: 273-7. 7 Berris B, Feinmann SV. Thyroid dysfunction and liver injury following alpha-interferon treatment of chronic viral hepatitis. D g Dis Sci 36: 1657-60. 8 Magrin S, Craxi A, Fiorentino G. Is autoimmune chronic active hepatitis a HCV related disease? J Hepatol 1991; 13: 128-31. 9 Haddad J, Deny P, Munz C, et al. Chronic lymphocytic sialadenitis characteristic of Sj6gren's syndrome in patients with HCV chronic hepatitis or cirrhosis. Lancet (accepted for publication). 10 Prentice LM, Phillips DIW, Sarsero D, Beever K, McLachlan S, Smith BR. Geographical distribution of subclinical autoimmune thyroid disease in Britain: a study using highly sensitive direct assays for autoantibodies to thyroglobulin and thyroid peroxidase. Acta Endocrinol 1990; 123: 493-8. HEPAT 01260 Azygos and hepatic extraction of atrial natriuretic factor (ANF) in patients with cirrhosis No evidence of reduced disposal Atrial natriuretic factor (ANF) ils a circulating hor- mone with natriuretic and vasodilating effects, which has been reported to be decreased, normal or elevated in different patients with cirrhosis. Thus, Hollister et al. (I) and Moreau et al. (2) have suggested that decreased splanchnic removal plays a role in the abnormal evels of ANF  reported in some patients with cirrhosis. Recently, we found a normal hepato-enteric clearance in patients with cirrhosis (274+46 vs 237+46 ml/min in controls, n.s.) (3). As pointed out then, our results only accounted for disposal from those parts of the liver and intestine that are drained through the hepatic veins (2). Oesophageal varices are drained through the azygos vein. However, the extraction of ANF  in blood drained through this vein has hitherto not been investigated. The present investigation was therefore undertaken to determine azygos extraction of ANF  in patients with cirrhosis. We report results from 9 patients (age 52-68, mean 58 years) with biopsy-verified cirrhosis (8 alcoholic, 1 posthepatitic), who underwent hepatic and azygos vein catheterization. Fluid retention and ascites were present in 7 patients. Patients without fluid retention were not restricted as to diet, whereas those with ascites were put on a sodium diet of 40 mmol/day. Seven patients received diuretics. Six patients with minor disorders and unrestricted iet served as controls. Catheterization pro- cedure, flow measurements, assessment of extraction and clearance, and analysis of ANF  have been described in detail elsewhere (3-5). The mean arterial concentration of ANF  in the patients was similar to that of the controls (10.0 +1.4 vs. 9.6+2.8pmol/1, respectively, n.s.). As illustrated in Figure 1, a substantial arterio-azygos extraction (0.35+0.09) was present in patients with cirrhosis and directly correlated to the arterio-hepatic extraction (0.33+0.10, r=0.86, p<0.005). Azygos and hepato- enteric clearances of ANF  were similar (Table 1) and the TABLE 1 Splanchnic disposal of atrial natriuretic factor (ANFI in patients with cirrhosis and controls Azygos blood Hepatic blood EAN F EANF Azygos ANF flow flow Azygos Hepatic clearance (l/min) (I/min) (ml/min) Hepatoenteric ANF clearance (ml/min) Overall splanchnic ANF clearance (ml/min) Overall splanchnic ANF removal (pmol/min) Cirrhosis 0.97 1.29 0.35 0.33 235 (n=9) +0.09 +0.09 +0.09 +0.097 +75 Controls I. I0 0.53 33 b (n = 6) + 0.17 + 0.09 320 +146 347 +81 552 a __+91 380 +90 5.8 +1.8 3.3 +0.5 Mean + SEM. EAt~l: = arterial-venous extraction ratio of ANF. 'p=0.1. h Estimated from a normal azygos blood flow f 0.15 l/min and an extraction ratio of 0.5. 420 LETTERS TO THE EDITOR overall splanchnic learance and removal of ANF  were similar or slightly higher in the patients compared to controls. We did not find any significant relation between ANF extraction, clearance or removal rate, on the one hand, and S-bilirubin (r=0.18-0.37), S-albumin (1"= -0 .43  to -0.48)  or hepatic venous pressure gradient ( r=-0 .42  to -0.62),  on the other. Plasma levels of ANF  in our cirrhotic patients were similar to those in the control subjects. This may be due to the fact that control subjects were studied on an unrestricted diet and most patients were studied on dietary sodium restriction and while being treated with diuretics (which are known to decrease ANF  levels). This resulted in comparable arterial ANF  in the two groups. The present study shows substantial and similar extraction of ANF  in the azygos and hepato-enteric venous beds in patients with cirrhosis. Thus, a major part of the splanchnic inflow of ANF  is cleared through the superior collateral flow. This shows conclusively that the overall splanchnic removal of ANF  is not decreased in patients with cirrhosis as Hollister et al. have suggested (1). In fact, the overall splanchnic removal of ANF  tended to be somewhat higher in the patients than in the controls. ANF  is rapidly hydrolyzed by endopeptidase 24.11 and cleared by specific receptors identified in most vascular endothelial cells. The high ANF  extraction in azygos plasma, as found in the present study, is similar to extraction described in other tissues (1,2). Our finding, therefore, may suggest hat the degradation of ANF  in blood drained through the axygos venus bed is mediated EANF, azygos 1.0 0.5 / / / • / • / / 0/ /  / / / /  • / y" / ( o.o , ¶ i i i i o.o 0.5 / x=y / / / //. / / / / / / / / / / / / • / / / ,/ / / / I I EANF, hep I I 1.0  Fig. 1. Relationship between arterial-azygos venous (E^Nv. azygo,) and arterial-hepatic venous (EASE. h~) extraction ratio of ANF in 9 patients with cirrhosis (r = 0.86, p < 0.005; y = 0.83x + 0.07). by the same mechanisms (i.e. related to vascular struc- tures) as those described for other tissues. Jens H. Henriksen, Fiemming Bendtsen and Alexander L. Gerbes Departments of Clinical Physiology and Hepatology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark. t, d Department ofhzternal Medicine II, Klinikum Grosshadern, Ludwig Maximilian Univer- sity, Munich, Germany. References  I Hollister AS, Rodeheffer R J, White FJ et al. Clearance of atrial natriuretic factor by lung, liver, and kidney in human subjects and the dog. J Clin Invest 1989; 83: 623-8. 2 Moreau R, Pussord E, Brenard R, Goudin C, Berdeaux A, Lebrec D. Clearance of atrial natriuretic peptide in patients with cirrhosis. Role of liver failure. J Hepatol 1991; 13: 351-7. 3 Henriksen JH, Bendtsen F, Schiitten H J, Warberg J. Hepat ic -  intestinal disposal of endogenous human alpha atrial natriuretic factor 99-126 in patients with cirrhosis. Am J Gastroentroenterol 1990; 85:1155-9. 4 Henriksen JH, Bendtsen F, Gerbes AL. Splanchnic removal of human alpha-atrial natriuretic p ptide in humans: enhancement after food intake. Metabolism 1990; 39: 553-6. 5 Gerbes AL, Wernze H, Arendt RM et al. Atrial natriuretic factor (ANF) and renin-aldosterone in volume regulation of p e ts with cirrhosis. Hepatology 1989; 9: 417-22. 

Atrial natriuretic factor (ANF) and renin-aldosterone in volume regulation of patients with cirrhosis. Hepatology

Clearance of atrial natriuretic factor by lung, liver, and kidney in human subjects and the dog.

Clearance of atrial natriuretic peptide in patients with cirrhosis. Role of liver failure.

Hepaticintestinal disposal of endogenous human alpha atrial natriuretic factor 99-126 in patients with cirrhosis.

Splanchnic removal of human alpha-atrial natriuretic peptide in humans: enhancement after food intake. Metabolism

Azygos and hepatic extraction of atrial natriuretic factor (ANF) in patients with cirrhosis

http://epub.ub.uni-muenchen.de/5971/1/Gerbes_ALexander_5971.pdf

Azygos and hepatic extraction of atrial natriuretic factor (ANF) in patients with cirrhosis

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