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Biomedical subjects

L Blendis

Publications and source records attributed to L Blendis.

At least 37 records · Page 2Linked to original sources
PubMed2000

Haemodynamic, renal sodium handling, and neurohormonal effects of acute administration of low dose losartan, an angiotensin II receptor antagonist, in preascitic cirrhosis.

BACKGROUND: The renin-angiotensin system may be implicated in the subtle sodium handling abnormality in preascitic cirrhosis. AIMS: To assess the role of angiotensin II in sodium homoeostasis in preascitic cirrhosis, using losartan, its receptor antagonist. PATIENTS: Nine male, preascitic cirrhotic patients, and six age matched, healthy male controls. METHODS: A dose response study using 2.5, 5, 7.5, and 10 mg of losartan was performed on a daily 200 mmol sodium intake, followed by repeat studies with the optimal dose, 7.5 mg of losartan, to determine its effects on systemic and renal haemodynamics, renal sodium handling, and neurohumoral factors. RESULTS: Preascitic cirrhotic patients had significantly reduced baseline urinary sodium excretion compared with controls (154 (8) versus 191 (12) mmol/day, p<0.05), associated with significantly reduced systemic angiotensin II levels (6.0 (1.7) versus 39.5 (10.0) pmol/l, p=0.002). Losartan 7.5 mg normalised renal sodium handling in the preascitic cirrhotic patients (202 (12) mmol/day, p=0.05 versus baseline), without any change in systemic or renal haemodynamics, but with significantly increased systemic angiotensin II levels (7.8 (2.3) pmol/l, p=0.05 versus baseline). Losartan had no effect on renal sodium handling in controls. CONCLUSIONS: In preascitic cirrhotic patients, the subtle renal sodium retention, paradoxically associated with low systemic neurohumoral factor levels, is improved with low dose losartan, suggesting the involvement of angiotensin II via its direct action on the renal tubule.

Adult↗
PubMed1999

Long-term renal sodium handling in patients with cirrhosis treated with transjugular intrahepatic portosystemic shunts for refractory ascites.

PURPOSE: The long-term effects of transjugular intrahepatic portosystemic shunts on renal sodium excretion are not known. We sought to determine these long-term effects, as well as to measure the effects of a sodium load in patients who are free of ascites. SUBJECTS AND METHODS: Ten patients with cirrhosis who had been successfully treated with transjugular intrahepatic portosystemic stent shunt for refractory ascites were studied before the shunt and again at 6 and 14 months after the shunt while on a 22 mmol sodium/day diet. At 14 months they were also studied on a 200 mmol sodium/day diet for 7 days without diuretics. Renal sodium handling, central blood volume, neurohumoral factors, and hepatic function were measured. RESULTS: Sodium balance was negative at 6 months (urinary sodium excretion [mean +/- SD] 51 +/- 11 mmol/day versus 7 +/- 2 mmol/day pre-shunt; P < 0.05), was maintained at 14 months (22 +/- 4 mmol/day; P < 0.05 versus pre-shunt), and was associated with normalization of renin activity and aldosterone levels, but not norepinephrine levels, as well as significantly improved renal hemodynamic measurements. Sodium loading with 200 mmol/day resulted in weight gain associated with increased central blood volume and appropriate renal sodium handling in most but not all patients (urinary sodium excretion 188 +/- 14 mmol/day), despite persistent nonsuppressibility of sympathetic hyperactivity. CONCLUSIONS: In cirrhotic patients with refractory ascites treated with a transjugular intrahepatic portosystemic stent shunt, long-term renal sodium handling is improved. Adequate intravascular filling in ascites-free cirrhotic patients with normal portal pressure permits an improved but not normalized renal response to a sodium load, possibly due to persistently elevated sympathetic activity. Therefore, these patients should increase their sodium intake cautiously.

Adult↗
PubMed1999

Effects of ursodeoxycholic acid on systemic, renal and forearm haemodynamics and sodium homoeostasis in cirrhotic patients with refractory ascites.

Systemic arterial vasodilatation has been implicated in the pathogenesis of sodium retention in cirrhosis. Hydrophobic bile acids, which have vasodilatory actions, may be involved. Ursodeoxycholic acid, a hydrophilic bile acid, could potentially decrease systemic arterial vasodilatation, possibly due to its antioxidant effects, and improve sodium handling in cirrhosis. The effects of ursodeoxycholic acid on systemic, renal and forearm haemodynamics, liver function and renal sodium handling were assessed in vasodilated cirrhotic patients with refractory ascites treated with a transjugular intrahepatic porto-systemic shunt (TIPS). Eight cirrhotic patients with refractory ascites without TIPS placement served as controls for the sodium handling effects of ursodeoxycholic acid. From 1 month post TIPS, seven patients were studied before, after 1 month of treatment with ursodeoxycholic acid (15 mg.day-1.kg-1) and at 1 month follow-up. Lipid peroxidation products were used as indices of its antioxidant effects. Ursodeoxycholic acid caused a significant reduction in sodium excretion in both groups (P<0.05). This, in the post-TIPS patients (urinary sodium excretion: 35+/-8 mmol/day at 1 month versus 93+/-21 mmol/day at baseline, P<0.05), was due to a significant increase in sodium reabsorption proximal to the distal tubule (P<0.05), without any significant changes in systemic, renal or forearm haemodynamics, or in liver function. No significant change in lipid peroxidation products was observed. We conclude that: (i) in cirrhotic patients with refractory ascites, ursodeoxycholic acid causes sodium retention, (ii) the abnormality in sodium handling in the post-TIPS cirrhotic patients appears to be the result of a direct effect on the proximal nephron, suggesting that factors other than systemic vasodilatation also contribute to sodium retention in cirrhosis, (iii) caution should be exercised in administering ursodeoxycholic acid in cirrhotic patients with ascites.

Adult↗
PubMed1999

Role of cardiac structural and functional abnormalities in the pathogenesis of hyperdynamic circulation and renal sodium retention in cirrhosis.

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.

Adult↗
PubMed1998

The renal sympathetic and renin-angiotensin response to lower body negative pressure in well-compensated cirrhosis.

BACKGROUND & AIMS: Certain antinatriuretic hormonal systems may be involved in the subclinical sodium handling abnormality in preascitic cirrhosis. The aims of this study were to determine the following in preascitic cirrhosis: (1) basal activity of the renal sympathetic and renin-angiotensin systems and (2) the relationship between the response of these systems to lower body negative pressure and sodium excretion. METHODS: Seven preascitic cirrhotic patients and 9 age- and sex-matched controls were studied on a 150 mmol sodium per day diet. Systemic and renal hemodynamics, renal neurohormonal secretion rates, and sodium excretion were assessed before, during increasing levels of, and after lower body negative pressure, each for 30 minutes. RESULTS: Both groups responded with a significant decrease in central venous pressure (P < 0.01) that remained higher in the cirrhotics than in the controls throughout the study. Cirrhotics showed significant increases compared with controls in renal renin and angiotensin II secretion rates at -20 mm Hg of lower body negative pressure, which was associated with significant renal sodium retention (96 +/- 17 micromol/min vs. 218 +/- 21 micromol/min at baseline, P < 0.05), but there was no change in renal sympathetic activity. CONCLUSIONS: In preascitic cirrhosis, sodium retention occurs in response to lower body negative pressure, which was associated with increased renal renin-angiotensin activity. Stimulation of the intrarenal renin-angiotensin system may be the initial renal pathophysiological change causing sodium retention in cirrhosis.

Adaptation, Physiological↗
PubMed1998

Pathophysiology and treatment of hepatorenal syndrome.

Hepatorenal syndrome is a progressive oliguric renal failure complicating the course of advanced cirrhosis and ascites. Significant hemodynamic changes occur in these patients consisting of marked systemic arterial vasodilatation and renal vasoconstriction. Traditionally, the systemic arterial vasodilatation with the consequent underfilling of the effective arterial blood volume has been held responsible for the pathogenesis of the renal vasoconstriction. Recent data showing a dissociation between the extent of arterial underfilling and the development of renal dysfunction in these patients have lead to the proposal of a hepatorenal interaction directly causing the renal vasoconstriction, with arterial underfilling secondarily contributing further to the renal vasoconstriction. Diagnosis of hepatorenal syndrome remains one of exclusion. Treatment is largely ineffective except for liver transplantation, which unfortunately is not available to all patients because of their short survival. Prognosis is very poor once it has developed. Therefore, physicians should be alert to avoid precipitating factors in these patients. Recent development of new therapies such as the use of a transjugular intrahepatic portosystemic shunt or systemic vasoconstrictors appear promising, but their efficacy should be evaluated in prospective randomized controlled trials.

Disease Management↗
PubMed1997

The mechanism of the initial natriuresis after transjugular intrahepatic portosystemic shunt.

BACKGROUND & AIMS: The pathogenesis of the delayed natriuresis after transjugular intrahepatic portosystemic shunt (TIPS) insertion is unknown. This was studied to elucidate the mechanism involved. METHODS: In 12 patients with cirrhosis and refractory ascites after TIPS, systemic and renal hemodynamics, renal sodium handling, central blood volume, neurohumoral factors, and hepatic function were studied weekly after the shunt with the patients receiving a diet of 20 mmol sodium/day. RESULTS: Two weeks after TIPS, the initial natriuresis (4 +/- 1 to 18 +/- 3 mmol/day; P < 0.05) was associated with significant reductions in corrected sinusoidal pressure (24.4 +/- 1.8 to 7.5 +/- 0.4 mm Hg; P < 0.001), proximal renal tubular reabsorption of sodium (P = 0.05), and renin-angiotensin-aldosterone activity (P < 0.05), but with significant systemic vasodilatation (P < 0.05). At 4 weeks, negative sodium balance was achieved (52 +/- 21 mmol/day; P < 0.01), despite continued systemic arterial vasodilatation, associated with significant increases in total central and cardiac volumes (P < 0.05) and normalization of serum aldosterone levels (P < 0.01). Four late responders were significantly older (P = 0.01) and had significantly lower baseline glomerular filtration rates (P = 0.02). CONCLUSIONS: In cirrhosis, sinusoidal portal hypertension and an activated renin-angiotensin-aldosterone system seem to be important in the pathogenesis of sodium retention. Systemic vasodilatation without arterial underfilling does not prevent natriuresis. Delayed natriuresis after TIPS is associated with increasing age and pre-TIPS renal impairment.

Adult↗
PubMed1997

Review: the controversy over the pathophysiology of ascites formation in cirrhosis.

The pathogenesis of renal sodium retention and ascites formation in cirrhosis is a subject of much controversy. The generally accepted 'peripheral arterial vasodilatation hypothesis' seems to best explain the mechanism of sodium retention and other clinical findings, such as the hyperdynamic circulation of cirrhosis. However, recent data in pre-ascites and in early ascites do not seem to conform to the peripheral arterial vasodilatation hypothesis. Sodium handling abnormalities can be demonstrated in pre-ascitic cirrhosis when patients are challenged with a sodium load, in the absence of systemic vasodilatation or arterial underfilling. Therefore, an alternative hypothesis with a direct hepatorenal interaction, acting via sinusoidal portal hypertension and/or hepatic dysfunction as the affector mechanism, is proposed to be the initiating event in renal sodium retention in cirrhosis. The second and later process is the development of systemic arterial vasodilatation, possibly due to the presence of excess systemic vasodilators and/or decreased responsiveness of the vasculature to endogenous vasoconstrictors. This, in turn, will lead to a relatively underfilled circulation with consequent activation of neurohumoral systems, promoting further renal sodium retention as described by the peripheral arterial vasodilatation hypothesis and ultimately leading to ascites. When compensatory natriuretic mechanisms fail, refractory ascites develops and hepatorenal syndrome sets in. Thus, renal sodium retention in cirrhosis is the result of interplay of many factors, with direct hepatorenal interaction predominating in earlier stages of the cirrhotic process, while systemic vasodilatation becomes a more important pathogenetic factor as the disease progresses.

Ascites↗