The Experts below are selected from a list of 19689 Experts worldwide ranked by ideXlab platform
Bruno Vogt - One of the best experts on this subject based on the ideXlab platform.
-
epithelial Sodium channel enac subunit mrna and protein expression in rats with puromycin aminonucleoside induced nephrotic syndrome
Clinical Science, 2003Co-Authors: Annette Audige, Brigitte M Frey, Dominik E Uehlinger, Felix J Frey, Bruno VogtAbstract:In experimental nephrotic syndrome, urinary Sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt Retention has not been completely elucidated. The rate-limiting constituent of collecting duct Sodium transport is the epithelial Sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary Sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary Sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium Retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded Sodium Retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of Sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced Sodium Retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.
-
glycyrrhetinic acid decreases plasma potassium concentrations in patients with anuria
Journal of The American Society of Nephrology, 2002Co-Authors: Andreas L Serra, Brigitte M Frey, Dominik E Uehlinger, Felix J Frey, Paolo Ferrari, Bernhard Dick, Bruno VogtAbstract:ABSTRACT. Licorice-associated hypertension is thought to be due to increased renal Sodium Retention. The active compound of licorice, glycyrrhetinic acid (GA), inhibits renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) and by that mechanism increases access of cortisol to the mineralocorticoid receptor that causes renal Sodium Retention and potassium loss. In addition, a direct vascular effect of 11beta-HSD activity has recently been incriminated to promote hypertension, a contention based on in vitro observations. This investigation was designed to establish whether this extrarenal effect of 11beta-HSD is relevant for BP regulation and potassium concentrations in plasma. In a prospective, double-blind, cross-over study, seven patients with anuria on chronic hemodialysis were randomly assigned after a baseline period of 2 wk to placebo or GA (1 g/d) for 2 wk, separated by a washout phase of 3 wk. The ratio of plasma cortisol/cortisone, determined by gas chromatography-mass spectrometry, increased in all patients after GA intake (F = 9.705; P < 0.004), which indicates inhibition of 11beta-HSD. Twenty-four-hour BP values did not change throughout the study. The increase of the plasma cortisol/cortisone ratio was paralleled by a decline in the plasma potassium concentration in every patient. The mean +/- SD plasma potassium concentration decreased from 5.5 +/- 0.6 mM/L at baseline to 4.9 +/- 0.7 and 4.5 +/- 0.8 mM/L after 1 and 2 wk on GA, respectively (F = 9.934, P < 0.003). Extrarenal 11beta-HSD activity influences serum potassium concentrations but does not regulate BP independently of renal Sodium Retention.
Claus Bistrup - One of the best experts on this subject based on the ideXlab platform.
-
urokinase type plasminogen activator contributes to amiloride sensitive Sodium Retention in nephrotic range glomerular proteinuria in mice
Acta Physiologica, 2019Co-Authors: Gitte R Hinrichs, Kathrin Weyer, Ulla G Friis, Per Svenningsen, Ida K Lund, Rikke Nielsen, Geraldine Mollet, Corinne Antignac, Claus BistrupAbstract:Aim Activation of Sodium reabsorption by urinary proteases has been implicated in Sodium Retention associated with nephrotic syndrome. The study was designed to test the hypothesis that nephrotic proteinuria in mice after conditional deletion of podocin leads to urokinase-dependent, amiloride-sensitive plasmin-mediated Sodium and water Retention. Methods Ten days after podocin knockout, urine and faeces were collected for 10 days in metabolic cages and analysed for electrolytes, plasminogen, protease activity and ability to activate γENaC by patch clamp and western blot. Mice were treated with amiloride (2.5 mg kg-1 for 2 days and 10 mg kg-1 for 2 days) or an anti-urokinase-type plasminogen activator (uPA) targeting antibody (120 mg kg-1 /24 h) and compared to controls. Results Twelve days after deletion, podocin-deficient mice developed significant protein and albuminuria associated with increased body wt, ascites, Sodium accumulation and suppressed plasma renin. This was associated with increased urinary excretion of plasmin and plasminogen that correlated with albumin excretion, urine protease activity co-migrating with active plasmin, and the ability of urine to induce an amiloride-sensitive inward current in M1 cells in vitro. Amiloride treatment in podocin-deficient mice resulted in weight loss, increased Sodium excretion, normalization of Sodium balance and prevention of the activation of plasminogen to plasmin in urine in a reversible way. Administration of uPA targeting antibody abolished urine activation of plasminogen, attenuated Sodium accumulation and prevented cleavage of γENaC. Conclusions Nephrotic range glomerular proteinuria leads to urokinase-dependent intratubular plasminogen activation and γENaC cleavage which contribute to Sodium accumulation.
-
reduced activity of 11beta hydroxysteroid dehydrogenase type 2 is not responsible for Sodium Retention in nephrotic rats
Acta Physiologica Scandinavica, 2005Co-Authors: Boye L Jensen, Claus Bistrup, Helle C Thiesson, Ole SkottAbstract:Aim: In mineralocorticoid target cells 11-beta-hydroxysteroid dehydrogenase type 2 (11βHSD2) converts glucocorticoids into non-active metabolites thereby protecting the mineralocorticoid receptor (MR) from stimulation by glucocorticoids. In nephrotic syndrome, a decreased activity of 11βHSD2 has been suggested to allow glucocorticoids to stimulate MR, thereby contributing to Sodium Retention. We tested this hypothesis in the puromycin aminonucleoside model of nephrotic syndrome in rats. Methods: Complete Sodium and potassium intakes and excretions (faeces and urine) were measured in rats in metabolic cages. RNase protection assay of mRNA and Western blotting of protein were used to estimate renocortical expression of 11βHSD2 and of the MR downstream effector serum and glucocorticoid induced kinase (SGK). In an intervention series, dexamethasone was given [10 μg (100 g bw)−1] to suppress endogenous glucocorticoids in the proteinuric stage during active Sodium Retention. Results: Nephrotic rats developed proteinuria, positive Sodium balance, decreased plasma aldosterone concentration, and decreased urinary Na+/K+ ratio. 11βHSD2 mRNA expression was down-regulated but protein expression was unchanged. SGK mRNA and phosphorylated SGK protein were up-regulated while total SGK protein expression was unchanged. Dexamethasone treatment, which suppressed plasma corticosterone concentration, did not correct Sodium balance or fluid Retention in nephrotic rats. Conclusion: Our results do not support the hypothesis that stimulation of the MR by endogenous glucocorticoids induces Sodium and fluid Retention in experimental nephrotic syndrome in rats.
Felix J Frey - One of the best experts on this subject based on the ideXlab platform.
-
epithelial Sodium channel enac subunit mrna and protein expression in rats with puromycin aminonucleoside induced nephrotic syndrome
Clinical Science, 2003Co-Authors: Annette Audige, Brigitte M Frey, Dominik E Uehlinger, Felix J Frey, Bruno VogtAbstract:In experimental nephrotic syndrome, urinary Sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt Retention has not been completely elucidated. The rate-limiting constituent of collecting duct Sodium transport is the epithelial Sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary Sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary Sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium Retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded Sodium Retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of Sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced Sodium Retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.
-
chenodeoxycholic acid and deoxycholic acid inhibit 11β hydroxysteroid dehydrogenase type 2 and cause cortisol induced transcriptional activation of the mineralocorticoid receptor
Journal of Biological Chemistry, 2002Co-Authors: Anita T Stauffer, Felix J Frey, Bernhard Dick, Mascha K Rochat, Alex OdermattAbstract:Abstract Inappropriate activation of the mineralocorticoid receptor (MR) results in renal Sodium Retention and potassium loss in patients with liver cirrhosis. Recent evidence suggested that this MR activation is, at least in part, a result of bile acid-dependent reduction in 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) activity, an enzyme preventing cortisol-dependent activation of MR by converting cortisol to cortisone. Here, we investigated the molecular mechanisms underlying bile acid-mediated MR activation. Analysis of urinary bile acids from 12 patients with biliary obstruction revealed highly elevated concentrations of chenodeoxycholic acid (CDCA), cholic acid (CA), and deoxycholic acid (DCA), with average concentrations of 50–80 μm. Although CDCA and DCA both mediated nuclear translocation of MR in the absence of 11βHSD2 and steroids in transiently expressing HEK-293 cells, the transcriptional activity of MR was not stimulated. In contrast, CDCA and DCA both inhibited 11βHSD2 with IC50 values of 22 and 38 μm, respectively and caused cortisol-dependent nuclear translocation and increased transcriptional activity of MR. LCA, the bile acid that most efficiently inhibited 11βHSD2, was present at very low concentrations in cholestatic patients, whereas the weak inhibitor CA did not cause MR activation. In conclusion, these findings indicate that CDCA, and to a lesser extent DCA, by inhibiting 11βHSD2, mediate cortisol-dependent nuclear translocation and transcriptional activation of MR and are responsible at least for a part of the Sodium Retention and potassium excretion observed in patients with biliary obstruction.
-
glycyrrhetinic acid decreases plasma potassium concentrations in patients with anuria
Journal of The American Society of Nephrology, 2002Co-Authors: Andreas L Serra, Brigitte M Frey, Dominik E Uehlinger, Felix J Frey, Paolo Ferrari, Bernhard Dick, Bruno VogtAbstract:ABSTRACT. Licorice-associated hypertension is thought to be due to increased renal Sodium Retention. The active compound of licorice, glycyrrhetinic acid (GA), inhibits renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) and by that mechanism increases access of cortisol to the mineralocorticoid receptor that causes renal Sodium Retention and potassium loss. In addition, a direct vascular effect of 11beta-HSD activity has recently been incriminated to promote hypertension, a contention based on in vitro observations. This investigation was designed to establish whether this extrarenal effect of 11beta-HSD is relevant for BP regulation and potassium concentrations in plasma. In a prospective, double-blind, cross-over study, seven patients with anuria on chronic hemodialysis were randomly assigned after a baseline period of 2 wk to placebo or GA (1 g/d) for 2 wk, separated by a washout phase of 3 wk. The ratio of plasma cortisol/cortisone, determined by gas chromatography-mass spectrometry, increased in all patients after GA intake (F = 9.705; P < 0.004), which indicates inhibition of 11beta-HSD. Twenty-four-hour BP values did not change throughout the study. The increase of the plasma cortisol/cortisone ratio was paralleled by a decline in the plasma potassium concentration in every patient. The mean +/- SD plasma potassium concentration decreased from 5.5 +/- 0.6 mM/L at baseline to 4.9 +/- 0.7 and 4.5 +/- 0.8 mM/L after 1 and 2 wk on GA, respectively (F = 9.934, P < 0.003). Extrarenal 11beta-HSD activity influences serum potassium concentrations but does not regulate BP independently of renal Sodium Retention.
Laurence M. Blendis - One of the best experts on this subject based on the ideXlab platform.
-
The mechanism of improved Sodium homeostasis of low-dose losartan in preascitic cirrhosis
Hepatology (Baltimore Md.), 2002Co-Authors: Florence Wong, Peter Liu, Laurence M. BlendisAbstract:Abstract Renal Sodium Retention on standing is one aspect of the abnormal renal Sodium handling in preascitic, well-compensated patients with cirrhosis. Recently, it has been shown that low doses (7.5 mg) of the angiotensin II (Ang II) receptor antagonist, losartan, can reverse renal Sodium Retention on high, 200-mmol Sodium/d diet in these patients and restore them to Sodium balance. Therefore, the effect of 7.5 mg of losartan on Sodium excretion, when changing from supine to erect posture for 2 hours, was examined in 10 well-compensated patients with cirrhosis and 9 age- and sex-matched controls on the same Sodium diet, under strictly controlled metabolic conditions. In contrast to control subjects, in whom Sodium excretion was unaffected, single 7.5-mg doses of losartan again restored the preascitic patients with cirrhosis to Sodium balance. In addition, it blunted the fall in erect posture– induced renal Sodium excretion by a reduction in proximal and distal tubular reabsorption of Sodium. These changes occurred without any significant changes in blood volumes, systemic and renal hemodynamics, or glomerular filtration rate (GFR) and filtered Sodium load compared with controls, and despite activation of the systemic renin-angiotensin-aldosterone system, which was still within normal levels. In conclusion, the beneficial natriuretic effects of low-dose losartan on erect posture – induced Sodium Retention in preascitic cirrhosis supports the suggestion that the pathophysiology of Sodium Retention in preascites is in part caused by an intrarenal tubular effect of Ang II in that posture. (H EPATOLOGY 2002;35:1449-1458.)
-
The mechanism of improved Sodium homeostasis of low-dose losartan in pre-ascitic cirrhosis
Journal of Hepatology, 2002Co-Authors: Florence Wong, Peter Liu, Laurence M. BlendisAbstract:Renal Sodium Retention on standing is one aspect of the abnormal renal Sodium handling in preascitic, well-compensated patients with cirrhosis. Recently, it has been shown that low doses (7.5 mg) of the angiotensin II (Ang II) receptor antagonist, losartan, can reverse renal Sodium Retention on high, 200-mmol Sodium/d diet in these patients and restore them to Sodium balance. Therefore, the effect of 7.5 mg of losartan on Sodium excretion, when changing from supine to erect posture for 2 hours, was examined in 10 well-compensated patients with cirrhosis and 9 ageand sex-matched controls on the same Sodium diet, under strictly controlled metabolic conditions. In contrast to control subjects, in whom Sodium excretion was unaffected, single 7.5-mg doses of losartan again restored the preascitic patients with cirrhosis to Sodium balance. In addition, it blunted the fall in erect posture– induced renal Sodium excretion by a reduction in proximal and distal tubular reabsorption of Sodium. These changes occurred without any significant changes in blood volumes, systemic and renal hemodynamics, or glomerular filtration rate (GFR) and filtered Sodium load compared with controls, and despite activation of the systemic renin-angiotensinaldosterone system, which was still within normal levels. In conclusion, the beneficial natriuretic effects of low-dose losartan on erect posture – induced Sodium Retention in preascitic cirrhosis supports the suggestion that the pathophysiology of Sodium Retention in preascites is in part caused by an intrarenal tubular effect of Ang II in that posture. (HEPATOLOGY 2002; 35:1449-1458.)
-
role of cardiac structural and functional abnormalities in the pathogenesis of hyperdynamic circulation and renal Sodium Retention in cirrhosis
Clinical Science, 1999Co-Authors: Florence Wong, Peter Liu, Lesley Lilly, Arieh Bomzon, Laurence M. BlendisAbstract:The aim of this study was to assess the relationship between subtle cardiovascular abnormalities and abnormal Sodium handling in cirrhosis. A total of 35 biopsy-proven patients with cirrhosis with or without ascites and 14 age-matched controls underwent two-dimensional echocardiography and radionuclide angiography for assessment of cardiac volumes, structural changes and systolic and diastolic functions under strict metabolic conditions of a Sodium intake of 22 mmol/day. Cardiac output, systemic vascular resistance and pressure/volume relationship (an index of cardiac contractility) were calculated. Eight controls and 14 patients with non-ascitic cirrhosis underwent repeat volume measurements and the pressure/volume relationship was re-evaluated after consuming a diet containing 200 mmol of Sodium/day for 7 days. Ascitic cirrhotic patients had significant reductions in (i) cardiac pre-load (end diastolic volume 106+/-9 ml; P<0.05 compared with controls), due to relatively thicker left ventricular wall and septum (P<0.05); (ii) afterload (systemic vascular resistance 992+/-84 dyn.s.cm(-5); P<0. 05 compared with controls) due to systemic arterial vasodilatation; and (iii) reversal of the pressure/volume relationship, indicating contractility dysfunction. Increased cardiac output (6.12+/-0.45 litres/min; P<0.05 compared with controls) was due to a significantly increased heart rate. Pre-ascitic cirrhotic patients had contractile dysfunction, which was accentuated when challenged with a dietary Sodium load, associated with renal Sodium Retention (urinary Sodium excretion 162+/-12 mmol/day, compared with 197+/-12 mmol/day in controls; P<0.05). Cardiac output was maintained, since the pre-load was normal or increased, despite a mild degree of ventricular thickening, indicating some diastolic dysfunction. We conclude that: (i) contractile dysfunction is present in cirrhosis and is aggravated by a Sodium load; (ii) an increased pre-load in the pre-ascitic patients compensates for the cardiac dysfunction; and (iii) in ascitic patients, a reduced afterload, manifested as systemic arterial vasodilatation, compensates for a reduced pre-load and contractile dysfunction. Cirrhotic cardiomyopathy may well play a pathogenic role in the complications of cirrhosis.
Florence Wong - One of the best experts on this subject based on the ideXlab platform.
-
natriuretic and aquaretic effects of intravenously infused calcium in preascitic human cirrhosis physiopathological and clinical implications
Gut, 2007Co-Authors: G Sansoe, Florence WongAbstract:Preascitic cirrhosis is characterized by subtle renal Sodium Retention. Calcium inhibits Na + - K + -2Cl - cotransport in the Henle9s loop and could potentially correct Sodium handling abnormalities at that site. We investigated the effects of calcium infusion on Sodium handling in ten pre- ascitic cirrhotics and nine healthy controls after one week of Sodium loading of 200 mmol Sodium/day. All subjects underwent a 3-hour supine determination of inulin, para-aminohippurate, lithium and free-water clearances, absolute and fractional excretions of Sodium, potassium and calcium, and plasma concentrations of renin, aldosterone, norepinephrine and vasopressin. The same were repeated over a further 3-hour supine period including 60 min i.v. infusion of 33 mg/min calcium gluconate. After Sodium loading, the 24-hour urinary Sodium excretion in the cirrhotics was lower than that in controls (P<0.03). Calcium infusion significantly decreased plasma norepinephrine levels (p<0.03), and induced greater increases in fractional delivery of Sodium to the Henle9s loop (p<0.5) in the cirrhotics compared to controls, associated with a decreased fractional reabsorption of Sodium beyond the proximal tubule (P<0.03), resulting in greater urinary volume, Sodium excretion and free-water clearance in the cirrhotics compared to controls (all P<0.05). Since the aldosterone-driven potassium secretion, as assessed by the computation of tubular- capillary gradient of [K+] in the collecting duct, was similar in the two groups, and unaffected by calcium, Sodium Retention must have occurred in the Henle9s loop in the cirrhotics. In conclusion, calcium is natriuretic in pre-ascitic cirrhosis. It also decreases norepinephrine release which may be responsible for decreased Sodium reabsorption in the Henle9s loop.
-
The mechanism of improved Sodium homeostasis of low-dose losartan in preascitic cirrhosis
Hepatology (Baltimore Md.), 2002Co-Authors: Florence Wong, Peter Liu, Laurence M. BlendisAbstract:Abstract Renal Sodium Retention on standing is one aspect of the abnormal renal Sodium handling in preascitic, well-compensated patients with cirrhosis. Recently, it has been shown that low doses (7.5 mg) of the angiotensin II (Ang II) receptor antagonist, losartan, can reverse renal Sodium Retention on high, 200-mmol Sodium/d diet in these patients and restore them to Sodium balance. Therefore, the effect of 7.5 mg of losartan on Sodium excretion, when changing from supine to erect posture for 2 hours, was examined in 10 well-compensated patients with cirrhosis and 9 age- and sex-matched controls on the same Sodium diet, under strictly controlled metabolic conditions. In contrast to control subjects, in whom Sodium excretion was unaffected, single 7.5-mg doses of losartan again restored the preascitic patients with cirrhosis to Sodium balance. In addition, it blunted the fall in erect posture– induced renal Sodium excretion by a reduction in proximal and distal tubular reabsorption of Sodium. These changes occurred without any significant changes in blood volumes, systemic and renal hemodynamics, or glomerular filtration rate (GFR) and filtered Sodium load compared with controls, and despite activation of the systemic renin-angiotensin-aldosterone system, which was still within normal levels. In conclusion, the beneficial natriuretic effects of low-dose losartan on erect posture – induced Sodium Retention in preascitic cirrhosis supports the suggestion that the pathophysiology of Sodium Retention in preascites is in part caused by an intrarenal tubular effect of Ang II in that posture. (H EPATOLOGY 2002;35:1449-1458.)
-
The mechanism of improved Sodium homeostasis of low-dose losartan in pre-ascitic cirrhosis
Journal of Hepatology, 2002Co-Authors: Florence Wong, Peter Liu, Laurence M. BlendisAbstract:Renal Sodium Retention on standing is one aspect of the abnormal renal Sodium handling in preascitic, well-compensated patients with cirrhosis. Recently, it has been shown that low doses (7.5 mg) of the angiotensin II (Ang II) receptor antagonist, losartan, can reverse renal Sodium Retention on high, 200-mmol Sodium/d diet in these patients and restore them to Sodium balance. Therefore, the effect of 7.5 mg of losartan on Sodium excretion, when changing from supine to erect posture for 2 hours, was examined in 10 well-compensated patients with cirrhosis and 9 ageand sex-matched controls on the same Sodium diet, under strictly controlled metabolic conditions. In contrast to control subjects, in whom Sodium excretion was unaffected, single 7.5-mg doses of losartan again restored the preascitic patients with cirrhosis to Sodium balance. In addition, it blunted the fall in erect posture– induced renal Sodium excretion by a reduction in proximal and distal tubular reabsorption of Sodium. These changes occurred without any significant changes in blood volumes, systemic and renal hemodynamics, or glomerular filtration rate (GFR) and filtered Sodium load compared with controls, and despite activation of the systemic renin-angiotensinaldosterone system, which was still within normal levels. In conclusion, the beneficial natriuretic effects of low-dose losartan on erect posture – induced Sodium Retention in preascitic cirrhosis supports the suggestion that the pathophysiology of Sodium Retention in preascites is in part caused by an intrarenal tubular effect of Ang II in that posture. (HEPATOLOGY 2002; 35:1449-1458.)
-
role of cardiac structural and functional abnormalities in the pathogenesis of hyperdynamic circulation and renal Sodium Retention in cirrhosis
Clinical Science, 1999Co-Authors: Florence Wong, Peter Liu, Lesley Lilly, Arieh Bomzon, Laurence M. BlendisAbstract:The aim of this study was to assess the relationship between subtle cardiovascular abnormalities and abnormal Sodium handling in cirrhosis. A total of 35 biopsy-proven patients with cirrhosis with or without ascites and 14 age-matched controls underwent two-dimensional echocardiography and radionuclide angiography for assessment of cardiac volumes, structural changes and systolic and diastolic functions under strict metabolic conditions of a Sodium intake of 22 mmol/day. Cardiac output, systemic vascular resistance and pressure/volume relationship (an index of cardiac contractility) were calculated. Eight controls and 14 patients with non-ascitic cirrhosis underwent repeat volume measurements and the pressure/volume relationship was re-evaluated after consuming a diet containing 200 mmol of Sodium/day for 7 days. Ascitic cirrhotic patients had significant reductions in (i) cardiac pre-load (end diastolic volume 106+/-9 ml; P<0.05 compared with controls), due to relatively thicker left ventricular wall and septum (P<0.05); (ii) afterload (systemic vascular resistance 992+/-84 dyn.s.cm(-5); P<0. 05 compared with controls) due to systemic arterial vasodilatation; and (iii) reversal of the pressure/volume relationship, indicating contractility dysfunction. Increased cardiac output (6.12+/-0.45 litres/min; P<0.05 compared with controls) was due to a significantly increased heart rate. Pre-ascitic cirrhotic patients had contractile dysfunction, which was accentuated when challenged with a dietary Sodium load, associated with renal Sodium Retention (urinary Sodium excretion 162+/-12 mmol/day, compared with 197+/-12 mmol/day in controls; P<0.05). Cardiac output was maintained, since the pre-load was normal or increased, despite a mild degree of ventricular thickening, indicating some diastolic dysfunction. We conclude that: (i) contractile dysfunction is present in cirrhosis and is aggravated by a Sodium load; (ii) an increased pre-load in the pre-ascitic patients compensates for the cardiac dysfunction; and (iii) in ascitic patients, a reduced afterload, manifested as systemic arterial vasodilatation, compensates for a reduced pre-load and contractile dysfunction. Cirrhotic cardiomyopathy may well play a pathogenic role in the complications of cirrhosis.
