sildenafil-citrate and Ascites

Protein-losing enteropathy (PLE) is a chronic condition involving multiple organ systems that may develop any time following Fontan completion. The pathogenesis of PLE is complex and multifactorial. Chronic venous hypertension, low cardiac output, and abnormal lymphatics may all play a role in the pathogenesis of PLE. Common signs and symptoms include chronic diarrhea, abdominal pain, and ascites. Diagnosis is based on the presence of signs and symptoms in addition to hypoalbuminemia and elevated stool alpha 1 antitrypsin. Early identification and a comprehensive approach to evaluation and treatment are important, as they may affect survival. The initial evaluation should include cardiac catheterization for hemodynamic assessment. Although an evidence base for treatment is lacking, various medical, interventional, and surgical approaches have been described with variable degrees of success. Commonly used therapies include nutritional support, diuretics, subcutaneous unfractionated heparin, budesonide, and sildenafil. Limited data exist for Fontan conversion or takedown. Assessment for heart transplantation should be considered. PLE mortality is high-approximately 50%-but may be mitigated by aggressive investigation and management. The evolving understanding of the role of lymphatics in the pathophysiology of PLE and the emerging role of interventional lymphatic procedures may further improve outcomes in this patient population.

Topics: Abdominal Pain; Academic Medical Centers; Ascites; Budesonide; Chronic Disease; Combined Modality Therapy; Diagnosis, Differential; Diarrhea; Diuretics; Female; Fontan Procedure; Heart Defects, Congenital; Heparin; Humans; Male; Prognosis; Protein-Losing Enteropathies; Rare Diseases; Risk Assessment; Sildenafil Citrate; Treatment Outcome

In the present study, we tested the hypothesis that inhibition of renal phosphodiesterase type 5 (PDE5) in patients with liver cirrhosis and ascites increases sodium excretion. The effect of sildenafil citrate was studied in a randomized double-blind. placebo-controlled crossover study. Diuretics were withdrawn, and a fixed sodium diet (100 mmol/day) was given to the patients for 5 days before both study days. After a 60-min basal period, eight patients received either oral sildenafil (50 mg) or placebo. Glomerular filtration rate (GFR) and renal blood flow (RBF) were determined by 99mTc-diethylenetriamine-pentaacetate and (131)I-hippuran clearances. In human nephrectomy specimens, PDE5 mRNA was expressed at similar levels in the cortex (n = 6) and inner medulla (n = 4). Histochemical staining showed PDE5 immunoreactivity in collecting ducts and vascular smooth muscle. At baseline, cirrhotic patients exhibited elevated plasma concentrations of ANP, renin, ANG II, and aldosterone that did not differ on the 2 study days. Basal sodium excretion was similar at the 2 study days (median 17 and 18 mmol, respectively), and patients were in positive sodium balance. Sildenafil increased heart rate, plasma renin activity, plasma ANG II, and aldosterone concentrations significantly after 60 min. Plasma cGMP concentration was increased after 120 and 180 min, and urinary sodium excretion and mean arterial blood pressure were decreased significantly at 120 and 180 min. Plasma ANP concentration, GFR, and RBF did not change after sildenafil. In patients with ascites and cirrhosis, inhibition of PDE5 did not promote natriuresis but led to increased plasma levels of the renin-angiotensin-aldosterone system.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Animals; Ascites; Blood Pressure; Cross-Over Studies; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Female; Gene Expression Regulation, Enzymologic; Hormones; Humans; Hypertension, Renal; Kidney Medulla; Liver Cirrhosis; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Potassium; Purines; Rats; Sildenafil Citrate; Sodium; Sodium Chloride, Dietary; Sulfones; Water

Topics: Aged; Ascites; Cardiac Catheterization; Diagnosis, Differential; Echocardiography; Female; Humans; Hypertension, Pulmonary; Hypoxia; Oxygen; Piperazines; Purines; Scleroderma, Limited; Sildenafil Citrate; Sulfones; Vasodilator Agents; Weight Loss