atrial-natriuretic-factor and Cholestasis

To investigate myocardial function in patients with obstructive jaundice before and after internal biliary drainage.. Increased plasma levels of atrial natriuretic peptide (ANP) have been found in patients with biliary obstruction.. Thirteen patients with newly diagnosed obstructive jaundice and no previous heart, lung, or renal disease were studied using a Swan-Ganz catheter. Hemodynamic measurements were taken before and 4 days after internal biliary drainage. Levels of ANP and brain natriuretic peptide (BNP) were obtained and liver function tests were also determined.. Plasma levels of ANP and BNP were increased twofold to fourfold in the basal state and declined after biliary drainage. Independent variables predicting left ventricular systolic work were total bilirubin concentrations, duration of jaundice, and BNP. In addition, bilirubin concentrations correlated with pulmonary vascular resistance, mean arterial pulmonary pressure, and right ventricular systolic work. Internal biliary drainage resulted in an improvement in left ventricular systolic work. A correlation was found between decreasing ANP concentrations and increasing cardiac output.. Increased plasma levels of natriuretic peptides in patients with obstructive jaundice may reflect a subclinical myocardial dysfunction correlating with the degree of jaundice. After internal biliary drainage, there is a measurable improvement of cardiac function.

Topics: Adult; Aged; Atrial Natriuretic Factor; Bilirubin; Blood Pressure; Cardiac Output; Cholestasis; Drainage; Female; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Artery; Stents; Vascular Resistance; Ventricular Function, Left

The purpose of this study was to assess the participation of the atrial natriuretic peptide (ANP)-cGMP system in electrolyte and volume handling of cholestatic rats submitted to an acute oral sodium load. Cholestasis was induced by ligation and section of the common bile duct (n = 51). Control rats were sham operated (n = 56). Three weeks after surgery, 24-hr urinary volume, sodium, potassium, cGMP and creatinine excretion were measured. Three days later, animals received 10 mmol/kg NaCl (1 M) by gavage, and urinary excretion was measured for 6 hr. In parallel groups of rats, plasma volume, electrolytes and ANP concentration, extracellular fluid volume (ECFV), and renal medullary ANP-induced cGMP production were determined in basal conditions or 1 hr after oral sodium overload. As compared with controls, cholestatic rats had a larger ECFV and higher plasma ANP (67.2 +/- 5.2 vs 39.7 +/- 3.5 pg/ml), but lower hematocrit and blood volume, and were hyponatremic. Cholestatic rats showed higher basal excretion of sodium, potassium, and volume than controls, but equal urinary cGMP. After the NaCl overload, cholestatic rats showed a reduced sodium excretion but equal urinary cGMP. One hr after sodium overload, both groups showed hypernatremia, but whereas in control rats ECFV and ANP increased (50.7 +/- 4.1 pg/ml), in cholestatic rats ECFV was unchanged, and plasma volume and ANP were reduced (37.5 +/- 5.8 pg/ml). ANP-induced cGMP production in renal medulla was similar in cholestatic and control nonloaded rats (14.2 +/- 5.2 vs 13.4 +/- 2.6 fmol/min/mg). One hr after the load, medullary cGMP production rose significantly in both groups, without difference between them (20.6 +/- 3.1 vs 22.7 +/- 1. 7 fmol/min/mg). We conclude that the blunted excretion of an acute oral sodium load in cholestatic rats is associated with lower plasma ANP due to differences in body fluid distribution and cannot be explained by renal refractoriness to ANP.

Topics: Animals; Atrial Natriuretic Factor; Bile Ducts; Blood Volume; Cholestasis; Creatinine; Cyclic GMP; Diuresis; Female; Hematocrit; Kidney Medulla; Ligation; Natriuresis; Potassium; Rats; Rats, Sprague-Dawley; Sodium; Urine

Hypovolaemia may cause renal dysfunction in obstructive jaundice. This study investigated whether, in patients with obstructive jaundice: (1) atrial natriuretic peptide (ANP) is increased; (2) fluid-regulating hormones are altered; and (3) biliary drainage improves fluid homoeostasis.. Forty-three patients with obstructive jaundice were investigated. A renal profile was obtained and levels of ANP, renin, aldosterone and vasopressin were determined. In a subset of 18 patients, studies were repeated 3 days after endoscopic biliary drainage and changes in extracellular volume were measured.. Creatinine clearance was impaired in ten of 30 patients. Patients with obstructive jaundice had higher mean levels of ANP (118 versus 40 pg/ml, P = 0.0001) and aldosterone (156 versus 43 pg/ml, P = 0.0001) than matched controls. Increased renin levels were observed in ten of the 43 patients and were associated with impaired creatinine clearance. After biliary drainage ANP concentration decreased (110 versus 67 pg/ml, P = 0.004) as well as aldosterone level (182 versus 85 pg/ml, P = 0.0002) and the mean extracellular volume increased (20.5 versus 23.1 per cent of body-weight, P = 0.001).. Plasma ANP concentration is increased in obstructive jaundice. Endocrine markers of hypovolaemia are activated in obstructive jaundice. After biliary drainage there is an improvement of endocrine and fluid derangements.

Topics: Aged; Aldosterone; Alkaline Phosphatase; Atrial Natriuretic Factor; Bile Duct Neoplasms; Biomarkers; Blood Volume; Cholestasis; Drainage; Endoscopy; Female; Humans; Longitudinal Studies; Male; Prospective Studies; Renin; Vasopressins

The alteration of the mechanisms of water and sodium preservation may be an important factor in the development of acute postoperative renal failure in obstructive jaundice (OJ). Experimental OJ has been associated with a depletion of the extracellular volume and alteration of the mechanisms of regulation of hydrosaline metabolism. The aim of this study was to evaluate the distribution of the body volumes and the regulating hormones of hydrosaline metabolism in human OJ.. A prospective, clinical study evaluating 18 patients with OJ (9 females and 9 males) with a mean age of 69 +/- 8.9 years was performed. The plasma levels of antinatriuretic peptide (ANP), aldosterone and renin were determined. The body volumes were evaluated by tetrapolar bioimpedanciometry. The results of the patients with OJ were compared with a control group (CG) of 12 healthy subjects, matched for age and sex (6 females and 6 males with a mean age of 64.5 +/- 14 years).. High ANP values were observed in 87.5% of the patients. The results of the hormonal studies compared with the CG were: ANP (117.33 +/- 37.7 vs 41.31 +/- 16.8 pg/ml; p < 0.001), aldosterone (185.68 +/- 82.1 vs 44.3 +/- 21.6 pg/ml; p < 0.001) and renine (57.18 +/- 69.9 vs 16.08 +/- 9.7 microU/ml; p < 0.05). Depletion of extracellular volume was found in 75% of the patients.. Human obstructive jaundice is associated with an important alteration in the hormonal mechanisms of water and sodium regulation. This alteration is accompanied by a marked depletion of extracellular volume.

Topics: Aged; Aged, 80 and over; Aldosterone; Atrial Natriuretic Factor; Body Fluid Compartments; Cholestasis; Extracellular Space; Humans; Kidney; Male; Middle Aged; Prospective Studies; Regression Analysis; Renin; Sodium; Water-Electrolyte Balance

Biliary obstruction in the rabbit causes increased release of atrial natriuretic peptide (ANP). Circulating bile, raised biliary pressure or absence of bile in the duodenum may be implicated in this hepatocardiac syndrome.. An experimental model was developed to elucidate the mechanism linking obstructive jaundice and increased plasma ANP. Hepatic and renal function, biliary tree pressure and ANP plasma concentrations were investigated in conscious rabbits 4 and 24 h after common bile duct ligation, biliovenous shunting or external drainage via a biliary fistula.. Bilirubin concentration increased after bile duct ligation and creation of a biliovenous shunt. Plasma creatinine increased abruptly in rabbits with a biliovenous shunt. At 4 h, the ANP increase in animals with a biliovenous shunt was ninefold that observed after bile duct obstruction while no change was noted after external biliary diversion (mean 350 versus 45 versus 9 fmol/l; P < 0.01). Relief of biliary tree obstruction was associated with a return of ANP levels towards basal normal values.. Raised plasma ANP in obstructive jaundice is not the result of an increased biliary pressure per se or absence of bile in the proximal duodenum but of the passage of bile components to the circulation.

Topics: Animals; Atrial Natriuretic Factor; Bile; Biliary Tract; Cholestasis; Male; Pressure; Rabbits

This study investigated the pathogenesis of water and sodium metabolism derangements in obstructive jaundice.. Obstructive jaundice is associated with hypodipsia, depletion of extracellular water, alterations of the water and sodium regulating hormones, and an increased incidence of renal failure. Plasma atrial natriuretic factor (ANF) increases after common bile duct ligation in the rabbit. The present study was designed to investigate ANF-secreting cardiac atrial cells in this animal model.. Plasma ANF and the percentage of atrial cells staining for ANF were determined in jaundiced and sham-operated rabbits at 24 (group OJ-24, n = 11; group SO-24, n = 5) and 72 hours (group OJ-72, n = 11; group SO-72, n = 5) after surgery. The atrial ANF content was also determined.. Plasma ANF was higher in jaundiced animals than in controls both at 24 (63 +/- 44 fmol/mL vs. 17 +/- 10 fmol/mL, p < 0.02) and at 72 hours (73 +/- 49 fmol/mL vs. 12 +/- 11 fmol/mL). In the two OJ groups, the percentage of positive ANF cells per 200-power field in the right atrial appendage was higher than in the SO groups both at 24 (62 +/- 11% vs. 31 +/- 12%, p < 0.003) and at 72 hours (56 +/- 18% vs. 31 +/- 12%, p < 0.01). Similar results were obtained in the right auricular wall. The percentage of positive ANF cells was significantly higher in the left atrium in which significant differences between the OJ and SO groups were also noted. The right atrial ANF content was higher in the OJ than in SO groups (437 +/- 323 pmol/mg of protein vs. 83 +/- 44 pmol/mg of protein).. Cardiac endocrine activity is increased in experimental obstructive jaundice. ANF may be involved in the pathogenesis of the renal and water and sodium metabolic disturbances present in this disease.

Topics: Animals; Atrial Natriuretic Factor; Cholestasis; Common Bile Duct; Common Bile Duct Diseases; Heart Atria; Ligation; Rabbits; Renal Insufficiency; Water-Electrolyte Imbalance

Renal response to atrial natriuretic peptide in chronic cholestasis was studied in anaesthetized rats and in their isolated perfused kidneys. Cholestasis was induced by bile duct section after ligature, while controls were sham operated. Three weeks after surgery, cholestatic rats showed moderate arterial hypotension, elevated diuresis and no differences in urinary sodium, glomerular filtration rate (GFR) and fractional sodium excretion (FENa), when compared to controls. Isolated kidneys of cholestatic rats had equal basal diuresis and less natriuresis than the controls. Cholestatic rats presented blunted natriuretic and diuretic responses to iv injections of atrial natriuretic peptide (ANP 0.5 microgram), associated with reduced increments in GFR and FENa, when compared with controls. Similarly, the diuretic-natriuretic response of isolated kidneys to ANP (3.5 x 10(-9) M) was greatly attenuated in this group. ANP did not increase perfusion pressure in cholestatic rats, as it did in controls. These results indicate that animals with chronic cholestasis present refractoriness to ANP, which might be mediated by a direct impairment at the renal vascular and tubular sites for ANP action.

Topics: Analysis of Variance; Animals; Atrial Natriuretic Factor; Cholestasis; Chronic Disease; Common Bile Duct; Diuresis; Female; Glomerular Filtration Rate; Kidney; Ligation; Male; Natriuresis; Rats; Rats, Sprague-Dawley; Renal Circulation; Vascular Resistance

Previous studies have shown that common bile duct ligation in the rabbit is followed by a reduction of the extracellular water compartment. To further elucidate the mechanisms leading to volume depletion in this model, water and sodium balances and changes in plasma concentrations of atrial natriuretic peptide (ANP), vasopressin (ADH), plasma renin activity (PRA) and aldosterone (Ald) were investigated during the first 4 days after common bile duct ligation (group OJ,) or sham operation (group SO). Water and chow intakes were lower in group OJ (148 +/- 30 versus 226 +/- 40 mL/4 days; p = 0.004 and 12 +/- 9 versus 171 +/- 40 g/4 days; p = 0.0001). There were no differences in urine output. Sodium urinary losses were marginally higher in group OJ (12.4 +/- 7 versus 6.7 +/- 5 mEq/4 days; p = 0.06). Water balance was lower in group OJ (-50 +/- 56 versus 101 +/- 71 mL/4 days; p = 0.0001). At 24 hours, plasma ANP (41 +/- 7 versus 10.7 +/- 1 fmol/mL, p = 0.0001), ADH (21.8 +/- 7 versus 12.3 +/- 6 pg/mL, p = 0.008) and Ald (14.5 +/- 5 versus 3.7 +/- 3 ng/dL, p = 0.001) were higher in group OJ. These alterations persisted 72 hours after bile duct ligation, when a concomitant increase in PRA (10.7 +/- 5 versus 3 +/- 1.6 ng/dL, p = 0.006) was also observed. A group of pair-fed pair-watered sham-operated controls (group SO2, n = 13) showed a metabolic profile similar to group OJ but a low ANP concentration. Multiple venous sampling in five rabbits 24 hours after bile duct ligation showed the highest plasma levels of ANP in the aorta and infrarenal vena cava. These results suggest that common bile duct ligation in the rabbit is followed by marked hypodipsia and hypophagia, possibly mediated by ANP, leading to isotonic volume depletion and secondary activation of the water and sodium retaining hormones.

Topics: Acute Kidney Injury; Aldosterone; Animals; Atrial Natriuretic Factor; Cholestasis; Common Bile Duct; Ligation; Male; Natriuresis; Rabbits; Renin; Time Factors; Vasopressins; Water-Electrolyte Balance; Water-Electrolyte Imbalance

Renal failure complicating obstructive jaundice (OJ) is probably linked to reduction of the extracellular water compartment. To elucidate the mechanism by which OJ leads to isotonic water depletion we studied a group of rabbits with OJ after common bile duct ligation (n = 17) and another group of sham operated rabbits (n = 14) for 10 days. Water intake and balance for two study periods (1-4 and 7-10 days after operation) were calculated. Renal function, sodium balance and plasma atrial natriuretic factor were determined on the fourth and tenth days after operation. Water intake and balance were lower in the OJ group both in the first study period (230 versus 519 ml/days 1-4, P less than 0.001; and -2.4 versus 219 ml/days 1-4, P less than 0.0001 respectively) and in the second study period (260 versus 865 ml/days 7-10, P less than 0.0001; and 11 versus 379 ml/days 7-10, P less than 0.0001 respectively). Sodium intake was negligible in the OJ group both on day four (0.73 versus 7.15 mM/24 h, P less than 0.0001) and on day 10 (0.78 versus 15.78 mM/24 h, P less than 0.0001). As a result plasma osmolality did not change. Day 10 urine osmolality and osmolar clearance were reduced in the OJ group (653 versus 1103 mOsm/kg, P less than 0.0001 and 0.09 versus 0.25 ml/min, P less than 0.0001 respectively) together with a decreased creatinine clearance (3 versus 11 ml/min, P less than 0.0001). Atrial natriuretic factor was increased in jaundiced rabbits (day 4, 22.7 versus 7.5 fmol/ml, P less than 0.0001; and day 10, 26.5 versus 11.2 fmol/ml, P less than 0.02). These findings suggest that OJ leads to an isotonic volume depletion resulting from abnormalities of the extracellular volume regulating mechanisms. These appear to be secondary to an inappropriate elevation of the atrial natriuretic factor plasma concentration.

Topics: Animals; Atrial Natriuretic Factor; Cholestasis; Common Bile Duct; Diuresis; Drinking; Kidney; Ligation; Rabbits; Sodium; Water-Electrolyte Balance

We determined if nine precirrhotic unanaesthetized dogs with chronic bile duct ligation (CBDL) responded uniformly to atrial natriuretic peptide (ANF) by infusing this peptide sequentially over 8-12 weeks at 175 ng.kg-1.min-1 and observing the natriuretic response. ANF was administered every 2 weeks post-CBDL until the 8th week and given again during the cirrhotic phase with ascites present (10-12 weeks post-CBDL). Sodium balance studies were conducted at similar time intervals. During the control period and at weeks, 2, 6, and 8 post-CBDL all dogs responded to ANF with a significant change in sodium excretion (delta UNaV, 50-240 mu equiv./min). At these times, all dogs were in sodium balance. At week 4 and during the ascitic period, heterogeneity of response to ANF was observed. In the former interval, five dogs responded (delta UNaV,75-230 mu equiv./min) and four did not, while in the latter interval, five dogs responded (delta UNaV, 50-240 mu equiv./min) and three did not (one dog died). In both time periods, there was severe urinary sodium retention (daily UNaV, 11 +/- 3 and 2 +/- 1 mequiv./day, respectively) while the dogs were ingesting 45 mequiv.Na+/day. The heterogeneity of natriuretic response was not correlated to plasma immunoreactive ANF, renin, or aldosterone levels. Plasma volume was significantly expanded from control during both intervals. We conclude that there is transient sodium retention during the 4th week post-CBDL, and that this period is associated with the heterogeneity of natriuretic response to ANF, despite the absence of ascites or edema.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Bile Ducts; Blood Volume; Cholestasis; Dogs; Glomerular Filtration Rate; Liver Cirrhosis, Experimental; Natriuresis; p-Aminohippuric Acid; Renin; Sodium