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Biomedical subjects

V Arroyo

Publications and source records attributed to V Arroyo.

At least 109 records · Page 6Linked to original sources
PubMed1994

Renal effects of natriuretic peptide receptor blockade in cirrhotic rats with ascites.

The aim of this study was to assess the effect of HS-142-1, a recently discovered specific antagonist of endogenous natriuretic peptides, on systemic hemodynamics, renal function, and the renin-aldosterone system in rats with cirrhosis and ascites. The study consisted of three protocols, each including 10 conscious control rats and 10 conscious rats with carbon-tetrachloride-induced cirrhosis with ascites. In protocol 1, HS-142-1 administration (by intravenous bolus of 20 mg.kg-1.body weight in all protocols) was not associated with significant changes in mean arterial pressure, heart rate, cardiac output or total peripheral resistance in the two groups of animals. In protocol 2, HS-142-1 induced a significant reduction in glomerular filtration rate (from 4.2 +/- 0.5 to 2.6 +/- 0.3 ml/min, p < 0.025) in control animals. A decrease in renal plasma flow and an increase in renal vascular resistance also occurred, but these changes were not statistically significant. In cirrhotic rats, HS-142-1 resulted in a significant decrease in renal plasma flow (from 10.9 +/- 0.7 to 4.3 +/- 0.6 ml/min, p < 0.001) and a significant increase in renal vascular resistance (from 6.0 +/- 0.6 to 16.3 +/- 2.7 mm Hg.min.ml-1, p < 0.025). Glomerular filtration rate decreased more in cirrhotic rats with ascites than in control rats (from 3.8 +/- 0.3 to 1.3 +/- 0.2 ml/min, p < 0.001). Changes in urine flow rate and urinary sodium excretion rate paralleled those of glomerular filtration rate in both groups of animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Renal impairment after spontaneous bacterial peritonitis in cirrhosis: incidence, clinical course, predictive factors and prognosis.

Although spontaneous bacterial peritonitis is considered a precipitating factor of renal impairment in cirrhosis, no study specifically addressing this problem has been reported. This study was aimed at assessing the incidence, clinical course, predictive factors and prognosis of renal impairment in cirrhotic patients with peritonitis. Therefore, 252 consecutive episodes of spontaneous bacterial peritonitis in 197 patients were analyzed. Clinical and laboratory data obtained before and after diagnosis of peritonitis were considered as possible predictors of renal impairment and hospital mortality. Renal impairment occurred in 83 (33%) episodes, and in every instance it fulfilled the criteria of functional kidney failure. Renal impairment was progressive in 35 episodes, steady in 27 and transient in 21. Blood urea nitrogen and serum sodium concentration before peritonitis and band neutrophils count in blood at diagnosis were independent predictors for the development of renal impairment. Renal impairment was the strongest independent predictor of mortality during hospitalization. Other independent prognostic factors were blood urea nitrogen level before peritonitis, age, positive ascitic fluid culture and serum bilirubin level during infection. These results indicate that renal impairment is a frequent event in cirrhotic patients with spontaneous bacterial peritonitis that occurs mainly in patients with kidney failure before infection. Renal impairment is the most important predictor of hospital mortality in cirrhotic patients with spontaneous bacterial peritonitis.

Adult↗
PubMed1994

Increased nitric oxide-dependent vasorelaxation in aortic rings of cirrhotic rats with ascites.

To assess whether aortic vessels of rats with cirrhosis and ascites possess an enhanced vascular response to endothelium-derived, nitric oxide-dependent vasodilators, we performed relaxation studies in isolated aortic rings of 21 control rats and 24 rats with carbon tetrachloride-induced cirrhosis and ascites. We carried out studies after contracting the vessels with norepinephrine. We measured endothelium-dependent vasodilator response by administering increasing concentrations of acetylcholine (10(-6) to 10(-2) mol/L) and ADP (10(-7) to 10(-4) mol/L). We evaluated endothelium-independent response by giving increased concentration of sodium nitrite (10(-5) to 10(-2) mol/L). The maximal absolute tension developed in response to norepinephrine was significantly decreased in cirrhotic rings (816 +/- 72 mg, p < 0.025) compared with control (1,425 +/- 75 mg) rings. Dose-response curves for endothelium-dependent vasodilators were shifted to the left in aortic rings of cirrhotic rats, and EC50 for acetylcholine and ADP were significantly decreased in cirrhotic (0.8 +/- 0.15 mmol/L and 0.42 +/- 0.16 mumol/L, p < 0.025 and p < 0.01, respectively) than in control rings (1.91 +/- 0.33 mmol/L and 3.09 +/- 0.82 mumol/L). In both acetylcholine- and ADP-stimulated vessels, differences between cirrhotic and control rings disappeared after nitric oxide synthesis inhibition with N omega-nitro-L-arginine (10(-4) mol/L). No difference in the relaxing effect of sodium nitrite was observed between cirrhotic and control rings. These results therefore demonstrate for the first time enhanced in vitro vascular responsiveness to nitric oxide-dependent vasodilators in rats with cirrhosis and ascites, giving further support to the concept that nitric oxide activity is increased in cirrhosis.

Acetylcholine↗
PubMed1994

Spontaneous bacterial peritonitis in liver cirrhosis: treatment and prophylaxis.

Spontaneous bacterial peritonitis in liver cirrhosis is due to the passage of intestinal bacteria into intestinal lymph vessels, systemic circulation and ascitic fluid. It may occur in patients with severe portal hypertension and hepatic failure, impaired reticuloendothelial phagocytic activity and low ascitic fluid opsonic activity. Spontaneous bacterial peritonitis is a monomicrobial infection usually caused by gram-negative bacteria. The treatment of choice of spontaneous bacterial peritonitis is cefotaxime. Several subgroups of cirrhotic patients have been shown to be predisposed to develop spontaneous bacterial peritonitis, including cases with gastrointestinal hemorrhage, patients with high serum bilirubin and low ascitic fluid protein concentration (< 1 g/dl), and patients who had recovered from an episode of spontaneous bacterial peritonitis. Since spontaneous bacterial peritonitis is associated with a relatively high in-hospital mortality rate (20-40%), prophylactic measures to prevent this infection are required. Short-term and long-term selective intestinal decontamination with oral norfloxacin has proved highly effective in preventing bacterial infection and spontaneous bacterial peritonitis in bleeding cirrhotic patients as well as recurrence of spontaneous bacterial peritonitis.

Cefotaxime↗
PubMed1994

Favorable effects of total paracentesis on splanchnic hemodynamics in cirrhotic patients with tense ascites.

Total paracentesis is widely used in the treatment of patients with cirrhosis and tense ascites. However, very little information is available regarding its consequences on splanchnic circulation, and its effects on portocollateral blood flow have not been investigated. Ten cirrhotic patients admitted because of tense ascites had measurements of hepatic and systemic hemodynamics, renal function and endogenous vasoactive neurohumoral systems at baseline, just after total paracentesis and 1 hr later. Total paracentesis caused a significant increase in cardiac output (+11%; 95% confidence interval, +4% to +19%) and a rapid fall in portal pressure, as shown by significant decreases in both the wedged hepatic venous pressure (-27% +/- 8%; p < 0.005) and the hepatic venous pressure gradient (-10%; 95% confidence interval, -3% to -18%). This was accompanied by a marked decrease in azygos blood flow (-28%; 95% confidence interval, -13% to -43%). These favorable hemodynamic effects were associated with a fall of the elevated levels of plasma renin activity (-47% +/- 9%; p < 0.05), plasma aldosterone (-31% +/- 21%; p < 0.05) and plasma norepinephrine and by a decrease in levels of serum creatinine (-24% +/- 15%; p < 0.05) and blood urea nitrogen (-4% +/- 3%; p < 0.05). These changes were maintained 1 hr later. This study indicates that in patients with cirrhosis and tense ascites total paracentesis favorably influences the systemic hemodynamics, portocollateral blood flow and portal pressure.

Aged↗
PubMed1994

Total paracentesis with dextran 40 vs diuretics in the treatment of ascites in cirrhosis: a randomized controlled study.

The aim of the current study was to compare total paracentesis associated with dextran-40 infusion with diuretics in the treatment of tense ascites in patients with cirrhosis. Eighty patients were randomly allocated to two groups: 40 patients were treated with paracentesis plus dextran-40 infusion (8 g per liter of ascitic fluid removed), and 40 patients with diuretics. After treatment patients were discharged with diuretics, and patients developing tense ascites during follow up (54 +/- 4 weeks) were treated according to their initial schedule. Paracentesis was more effective than diuretics in mobilizing the ascitic fluid. The incidence of complications was significantly higher (p < 0.05) in the diuretic group (38%) than in the paracentesis group (15%). This difference was mainly due to a higher incidence of hepatic encephalopathy in the former group (30% vs. 2.5%). A significantly higher incidence of hepatic encephalopathy was also observed in the diuretic group during the follow-up readmissions for ascites recurrence. There were no significant differences between the two treatment groups in the probability of survival after inclusion. Plasma renin activity and plasma aldosterone concentration measured before and 2 and 6 days after paracentesis in 20 randomly selected patients increased significantly (p < 0.05) (baseline values: 5.3 +/- 1.4 ng.ml-1.h-1 and 63 +/- 21 ng/dl; 48 h after paracentesis: 11.7 +/- 3.9 ng.ml-1.h-1 and 99 +/- 31 ng/dl; 6 days after paracentesis: 10.9 +/- 3 ng.ml-1.h-1 and 110 +/- 27 ng/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Blunted natriuretic response to human urine extracts with Na+,K(+)-ATPase inhibiting activity in experimental cirrhosis.

Human urine and plasma extracts contain a material that inhibits the enzyme Na+,K(+)-ATPase (the endogenous sodium pump) and produces natriuresis in the bioassay animal. This endogenous sodium pump inhibitor(s), also known as digitalis-like factor, is thought to be involved in sodium and extracellular fluid volume homeostasis. Increased urine and plasma sodium pump inhibiting activity have been reported in patients with cirrhosis and sodium retention. The aim of the study was to assess the renal response to i.v. administration (0.2 ml/min per kg bw for 10 min) of a human urine extract containing sodium pump inhibiting activity (28.5 nmol equivalent ouabain/ml) in eight conscious rats with cirrhosis and ascites and eight control rats. Baseline urinary excretion of Na+,K(+)-ATPase inhibiting activity was significantly higher in cirrhotic rats with ascites than in control rats (235 +/- 40 vs 91 +/- 16; p < 0.01). Human urine extract induced a significant (p < 0.05) increase in glomerular filtration rate in control (3.2 +/- 0.4 to 4.2 +/- 0.5 ml/min) and cirrhotic rats (3.0 +/- 0.3 to 4.0 +/- 0.5 ml/min). In control rats it also increased urinary sodium excretion (1.47 +/- 0.22 to 2.43 +/- 0.5 microEq/min, p < 0.01) and fractional sodium excretion (0.29 +/- 0.01 to 0.43 +/- 0.04%, p < 0.025). In contrast, in cirrhotic rats with ascites neither sodium excretion nor fractional sodium excretion was significantly affected. No changes were observed in plasma aldosterone and atrial natriuretic peptide concentrations in either group. These data suggest that in cirrhosis there is a renal resistance to the natriuretic effect of endogenous sodium pump inhibitor(s).

Animals↗
PubMed1994

Intracellular calcium concentration in vascular smooth muscle cells of rats with cirrhosis.

A decreased pressor response to endogenous vasoconstrictors, such as angiotensin II and vasopressin, is a characteristic finding in cirrhosis with ascites; this has been considered as partially responsible for the arteriolar vasodilation present in this disease. Previous investigations suggested that this abnormality is due to a post-receptor defect leading to altered intracellular Ca2+ mobilization. To assess this hypothesis, vascular responsiveness to angiotensin II (3.10(-8) M) and intracellular Ca2+ concentration in basal conditions and following angiotensin II (1-100 nM) and vasopressin stimulation (100 nM) were measured in aortic rings and in primary cultured aortic vascular smooth muscle cells, respectively. The study was carried out in 43 control rats and 40 rats with CCl4-induced cirrhosis and ascites. Cells were grown to confluence on glass cover slips and then loaded with Fura-2, a fluorescent intracellular Ca2+ indicator, for continuous monitoring of intracellular Ca2+ concentration. A decreased constrictor response to angiotensin II was detected in cirrhotic aortic rings in comparison to control rings (increase in tension: 31 +/- 5 vs 79 +/- 14 mg, p < 0.005). No differences in intracellular Ca2+ concentration between cirrhotic and control cells were observed in basal conditions (104 +/- 6 and 100 +/- 3 nM, respectively). Angiotensin II administration to cirrhotic vascular smooth muscle cells had a dose-dependent biphasic effect consisting of a rapid increase, followed by return to a sustained level significantly higher than the basal value. This response was identical to that observed in control vascular smooth muscle cells. Similar findings were obtained following vasopressin stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1994

A European survey on the treatment of ascites in cirrhosis.

A questionnaire to assess the clinical choice of ascites treatment in cirrhosis was distributed to 1473 participants in an EASL meeting. The response rate (295, 20%) was considered satisfactory in view of the heterogeneity of the persons attending this event. Most participants (86.4%) in the survey were hepatologists and gastroenterologists. The following conclusions of the survey are noteworthy: (1) The objective of ascites therapy was to eliminate completely or almost completely the ascitic fluid for 49% of responders and to decrease ascites volume to an acceptable level of patient comfort for 48%; (2) The classical progressive therapeutic schedule of ascites is rarely used; (3) Following mobilisation of ascites, most (82%) maintain patients on diuretic therapy to avoid reaccumulation of ascites; (4) Only 5% of participants did not use paracentesis to manage ascites in cirrhosis. This was the therapeutic procedure most frequently used for patients with refractory ascites; (5) Although the most acceptable definition of refractory ascites was ascites which cannot be mobilized by maximal medical treatment, a significant proportion of participants also considered that intractable ascites due to diuretic-induced complications and recidivant ascites should be included in the definition; (6) The proportions of participants prescribing prophylactic therapy, mainly low sodium diet, to compensated patients with and without a past history of ascites were 68% and 16%, respectively.

Ascites↗
PubMed1994

HS-142-1, a potent antagonist of natriuretic peptides in vitro and in vivo.

To determine whether HS-142-1 (HS), a potent atrial natriuretic peptide (ANP) receptor antagonist, also inhibits the effects of brain natriuretic peptide (BNP), urodilatin (URO), and C-type natriuretic peptide, in vitro studies were carried out, demonstrating that HS inhibited production of cGMP by rat fetal lung fibroblast cells induced by ANP, BNP, URO, and C-type natriuretic peptide. Acute clearance studies were conducted in euvolemic Munich-Wistar rats under inactin anesthesia to characterize the effects of HS in vivo. In response to ANP, BNP, or URO (4 micrograms/kg priming dose plus 0.5 micrograms/kg per minute for 20 min), urine flow, absolute sodium excretion rates, and fractional sodium excretion exhibited similar increases (four- to fivefold) in vehicle-treated rats; these responses were, however, completely abolished by prior HS treatment. The tendency for GFR to rise during the infusion of natriuretic peptides (NP) was also blocked after HS. By contrast, HS did not block the renal effects of L-arginine, a precursor of nitric oxide, or of furosemide. Furthermore, the inhibition of endogenous NP by HS was associated with small but significant reductions in GFR and absolute and fractional sodium excretion in normal rats under euvolemic but not hydropenic conditions. These studies provide evidence that the observed effects of HS in vivo and in vitro are mediated exclusively by receptors of NP. Together, these data support the view that HS is a highly specific ligand for NP receptors, capable of antagonizing the renal effects not only of exogenous ANP, but also those of BNP and URO.

Animals↗
PubMed1994

Impact of shunt surgery for variceal bleeding in the natural history of ascites in cirrhosis: a retrospective study.

Despite the efficacy of shunt surgery in the treatment of variceal bleeding, less effective nonoperative therapies are being substituted because surgical shunt does not modify survival and increases hepatic encephalopathy. However, the real impact of shunt surgery on the natural history of ascites and its complications has not been established. The course of 204 Child-Pugh A and B cirrhotic patients with variceal bleeding included in three controlled trials of our units who survived first hospitalization was updated. Ninety-eight patients (group I) were treated by portacaval (56 patients) or distal splenorenal (42 patients) shunt, whereas 106 (group II) were treated by nonshunt procedures (sclerotherapy in 89 patients and staple transection in 17 patients). As expected, the 5-yr probability of variceal rebleeding was lower (13% vs. 44%) and hepatic encephalopathy higher (50% vs. 28%) in group I than in group II, and survival was similar (67% vs. 60%). Shunt surgery had a great impact on the natural history of ascites and its complications. The probability of occurrence of ascites (15% vs. 73%; p < 0.0001), spontaneous bacterial peritonitis (2% vs. 21%; p < 0.0001) and hepatorenal syndrome (4% vs. 21%; p < 0.01) was greatly reduced. These beneficial effects accounted for the lower percentage patients requiring readmissions (51% vs. 70%; p = 0.02) and shorter total time spent in hospital (14 +/- 22 vs. 26 +/- 39 days/patient; p = 0.01) in group I. These data indicate that shunt surgery, in addition to reducing the probability of rebleeding, markedly decreases the probability of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome development.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites.

BACKGROUND: The aim of the study was to investigate the incidenc, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. METHODS: The study is a follow-up investigation in 234 nonazotemic patients with cirrhosis and ascites. Thirty-nine variables obtained at inclusion were analyzed as possible predictors of hepatorenal syndrome occurrence (Kaplan-Meier method, Mantel-Cox test, and step-wise Cox regression procedure). RESULTS: The probability of hepatorenal syndrome occurrence was 18% at 1 year and 39% at 5 years. Sixteen variables had predictive value for hepatorenal syndrome occurrence in the univariate analysis: history of ascites, hepatomegaly, nutritional status, blood urea nitrogen level, serum creatinine concentration, serum sodium and potassium concentration, serum and urine osmolality, urinary sodium excretion, free water clearance after a water load, glomerular filtration rate, arterial pressure, plasma renin activity, plasma norepinephrine concentration, and esophageal varices. Neither etiology (alcoholic vs. nonalcoholic) nor the Child-Pugh score had predictive value. A multivariate analysis disclosed only three independent predictors of hepatorenal syndrome occurrence: low serum sodium concentration, high plasma renin activity, and absence of hepatomegaly. CONCLUSIONS: The hepatorenal syndrome is a relatively frequent complication in cirrhotic patients with ascites that is associated with an extremely short survival. Liver size, plasma renin activity, and serum sodium concentration are predictors of hepatorenal syndrome occurrence in these patients.

Adult↗
PubMed1993

Circulating levels of endothelin in cirrhosis.

BACKGROUND: Current information concerning endothelin in cirrhosis is conflicting. Plasma endothelin concentration has been found to be increased in some studies and normal or reduced in others. The present study was aimed to investigate the plasma levels of endothelin in cirrhosis and to assess whether it is involved in the renal and hemodynamic disturbances and neurohumoral changes present in this condition. METHODS: Renal function, plasma renin activity, and plasma concentration of aldosterone, norepinephrine, antidiuretic hormone, atrial natriuretic factor, and endothelin were measured in 9 healthy subjects, 7 compensated cirrhotics, and 25 cirrhotics with ascites (10 with functional renal failure). RESULTS: Cirrhotics with ascites with and without functional renal failure showed higher endothelin levels (15.6 +/- 6.4 and 15.7 +/- 4.6 pg/mL, respectively; mean +/- SD) than compensated cirrhotics (6.4 +/- 1.8 pg/mL) and healthy subjects (3.4 +/- 1.0 pg/mL) (analysis of variance, F = 21.84; P < 0.001). These patients also showed higher plasma levels of renin, aldosterone, norepinephrine, antidiuretic hormone, and atrial natriuretic factor, although plasma endothelin levels only correlated significantly with plasma atrial natriuretic factor (r = 0.73, P < 0.001) and antidiuretic hormone concentrations (r = 0.59, P < 0.001). In 7 additional nonazotemic cirrhotics with ascites, plasma renin activity and the plasma concentration of aldosterone and endothelin were measured before and 24 hours after the intravenous administration of a saline solution of human serum albumin. Volume expansion markedly suppressed renin and aldosterone but not endothelin (21.03 +/- 7.34 vs. 23.97 +/- 14.29 pg/mL). CONCLUSIONS: Circulating plasma levels of endothelin are elevated in cirrhosis with ascites and do not decrease following plasma volume expansion.

Adult↗
PubMed1993

Oral misoprostol or intravenous prostaglandin E2 do not improve renal function in patients with cirrhosis and ascites with hyponatremia or renal failure.

Prostaglandins play an important role in the maintenance of renal hemodynamics and water excretion in cirrhosis. To investigate whether the administration of prostaglandins improves renal function in cirrhotic patients with ascites, 16 patients with functional renal failure and/or dilutional hyponatremia were given oral misoprostol, a prostaglandin E1 analogue (200 micrograms/6 h for 4 days; n = 9) or intravenous prostaglandin E2 (0.5 microgram/min for 1 h followed by 1 microgram/min for another hour; n = 7). The administration of misoprostol did not induce significant changes in the glomerular filtration rate (59 +/- 11 vs. 54 +/- 11 ml/min), sodium excretion (4.0 +/- 1.3 vs. 4.1 +/- 2.1 microEq/min), and free water clearance (2.4 +/- 0.8 vs. 2.1 +/- 0.9 ml/min), nor did it improve the natriuretic response to an intravenous bolus of 40 mg of furosemide (486 +/- 124 vs. 406 +/- 88 microEq/min). Similarly, an infusion of prostaglandin E2 did not induce significant changes in the glomerular filtration rate (baseline: 33 +/- 6; 0.5 microgram/min: 31 +/- 5; 1 microgram/min: 31 +/- 6 ml/min) and sodium excretion (5.7 +/- 2.7; 3.2 +/- 1.4; and 1.5 +/- 0.7 microEq/min, respectively), whereas free water clearance decreased significantly (1.1 +/- 0.7; 0.5 +/- 0.5; and -0.1 +/- 0.2 ml/min, respectively, p < 0.05). These results indicate that oral misoprostol or the intravenous infusion of prostaglandin E2 do not improve renal function in cirrhosis with ascites.

Administration, Oral↗