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Biomedical subjects

A Gatta

Publications and source records attributed to A Gatta.

At least 145 records · Page 8Linked to original sources

Effect of nadolol on liver haemodynamics and function in patients with cirrhosis.

Beta-adrenoceptor blockers used in the medical management of portal hypertension decrease liver blood flow. The sporadic onset of hepatic encephalopathy during propranolol treatment was ascribed to this decrease. The aim of the present study was to evaluate the effect of chronic treatment with nadolol on liver blood flow and liver function. Nadolol, a non-cardioselective beta-adrenoceptor blocker, has been reported to be as powerful as propranolol in decreasing portal pressure. Before and after 1 month of treatment with nadolol at a dose reducing heart rate by 25%, in 15 cirrhotic patients with portal hypertension, the following parameters were determined: hepatic venous pressure gradient, hepatic blood flow, galactose eliminating capacity, aminopyrine metabolic activity, ICG clearance and intrinsic hepatic clearance. Hepatic venous pressure gradient and hepatic blood flow were decreased by nadolol. However liver function was not affected by the drug. We conclude that, despite a lowered hepatic blood flow, liver function is not affected by 1 month of nadolol treatment.

Adult↗

Blood flow of experimental liver metastases in rat as evaluated by the locally injected 133-Xenon washout.

The investigations on blood flow in liver metastases are interesting from both a pathophysiological and a therapeutic point of view. Available data, however, are few and not definitive, as these studies are complex and difficult to perform. In a group of 25 Sprague-Dawley rats, in which liver metastases of Walker-256 carcinoma had been implanted, the blood flows in a metastasis and in the normal liver surrounding it were determined by means of the locally injected 133-Xenon washout. Thirteen sham-operated rats were a control group. Blood flow in the metastases was decreased as a group compared to that in the normal liver surrounding metastases and to that in liver of sham-operated rats. Small metastases showed normal or increased blood flow, large ones decreased or stagnant blood flow. Moreover, a significant inverse correlation was found between blood flow and diameter of metastasis. It is concluded that liver metastases of Walker-256 carcinoma show a decrease in blood flow which is related to the size of metastasis.

Animals↗

Renal water and sodium handling in compensated liver cirrhosis: mechanism of the impaired natriuresis after saline loading.

The present study was attempted to evaluate sodium and water balance in compensated liver cirrhosis. Renal sodium and water handling was studied in six cirrhotic patients without ascites and/or oedema and in six controls before and after saline loading. Fractional sodium reabsorption at the various nephron sites (proximal, diluting and distal) was evaluated by means of clearance techniques during maximal water diuresis and hypotonic saline infusion. Compensated cirrhotic patients showed a normal baseline sodium and water balance but a blunted natriuretic response when saline loaded (urinary sodium excretion after saline load = 338 +/- 290 compared to 933 +/- 504 mumol min-1 of controls; P less than 0.05). The impaired natriuresis was found to be related to an increased reabsorption of sodium in the proximal tubule (proximal fractional sodium reabsorption = 88.4 +/- 3.8 compared to 81.7 +/- 4.3% of controls; P less than 0.05). These findings confirm the hypothesis that renal sodium handling abnormalities might precede ascites formation. Additional studies, however, are necessary to further define renal factors mediating the increased reabsorption of sodium in compensated liver cirrhosis.

Adult↗

Splenic haemodynamics and portal hypertension in patients with liver cirrhosis and spleen enlargement.

The relationships between portal hypertension and spleen enlargement, in patients with liver cirrhosis, are not clearly defined; as well as those between splenic haemodynamics and portal hypertension. In 25 cirrhotics with spleen enlargement and portal hypertension and in seven controls, the following parameters were determined: estimated splenic volume (ESV) from the radiographic view of the spleen, according to Blendis, Williams and Kreel (1969), specific splenic blood-flow (SSBF), total splenic blood-flow (TSBF), porto-hepatic gradient (PHG), specific splenic resistance (SSR) and total splenic resistance (TSR). Moreover, the size and extension of oesophageal varices, at oesophagoscopy, were classified according to Dagradi (1973). PHG, ESV and TSBF were increased in all subjects, SSBF was increased in two cases, SSR was increased in two cases and decreased in two cases, TSR was decreased in all cases and ESV was not correlated to the level of portal hypertension. Neither TSBF nor TSR were found to be correlated to the level of portal hypertension, as estimated by PHG or by oesophageal varices. It is concluded that, in patients with liver cirrhosis and spleen enlargement, splenomegaly is likely to be the consequence of pulp hyperplasia and not of passive congestion, and that increases in splenic blood-flow do not contribute significantly to portal hypertension.

Adult↗

Are urinary enzymes useful markers of kidney damage in obstructive jaundice? An experimental study on Sprague-Dawley rats.

To evaluate the reliability of urinary enzymes as markers of renal tubular damage in obstructive jaundice, research was carried out on 26 Sprague-Dawley rats submitted to bile duct ligation and on 16 sham-operated rats. The fractional clearances of lysozyme (CfrLYS) and of malto-dehydrogenase (CfrMDH)-indices of tubular function-and the fractional excretions of gamma-glutamyltransferase (UfrGGT) and of alpha-glucosidase (UfrAGL)-indices of tubular anatomic damage - were measured 5, 10, 20 and 30 days after operation. Creatinine clearance, urinary sodium excretion, urinary potassium excretion, proteinuria, plasma bilirubin and bile acids were also measured. Kidneys were taken for histology. All rats submitted to common bile duct ligation had high levels of bilirubin and bile acids; proximal tubules were damaged and the extent of the lesions increased with time. However, creatinine clearance, urinary sodium excretion, proteinuria, CfrMDH and UfrAGL gave no indication of renal lesions, whereas CfrLYS and UfrGGT were significantly higher 20 and 30 days after bile duct ligation, respectively. These findings show that CfrLYS and UfrGGT could be useful tests for renal tubular lesions in jaundice.

Animals↗

Effect of somatostatin on splanchnic hemodynamics in patients with liver cirrhosis and portal hypertension.

The effect of somatostatin on splanchnic hemodynamics in patients with liver cirrhosis is not clearly defined, as some authors report a decrease in portal pressure and in liver blood flow during intravenous administration of this hormone, while others do not. In 19 subjects with liver cirrhosis and portal hypertension the following parameters were measured before and during intravenous administration of somatostatin (7.5 micrograms/min): porto-hepatic gradient, estimated hepatic blood flow, specific splenic blood flow, cardiac index. Estimated hepatic blood flow decreased significantly during somatostatin infusion (p less than 0.05), averaging a 13% decrease; porto-hepatic gradient, splenic specific blood flow and cardiac index did not vary significantly. These data indicate that somatostatin infused at a dose of 7.5 micrograms/min induces a slight decrease in liver blood flow without affecting portal hypertension.

Adult↗

Reference ranges and methodological aspects in the urinary measuring of lysozyme, malate-dehydrogenase, gamma-glutamyltransferase and alpha-glucosidase.

The urinary excretions of lysozyme (LYS), malate-dehydrogenase (MAD), gamma-glutamyltransferase (GGT) and alpha-glucosidase (AGL) were measured in a group of normal subjects in basic conditions, during forced diuresis, at different hours of the day and with urinary collection periods of different lengths. The results have been expressed in the principal ways used in clinical practice. The best way to express the excretions of GGT and AGL was with the fractional excretions. For LYS and MAD, the fractional clearances appeared to be theoretically valuable. They were not significantly influenced by sex or by the different urinary collections. Forced diuresis caused a significant scattering of enzymuria.

Adult↗

Use of a nonselective beta-blocker, nadolol, in the treatment of portal hypertension in cirrhotics.

Recently a medical treatment with propranolol has been proposed in order to decrease portal pressure and lessen the risk of recurrent gastrointestinal bleeding in cirrhotic patients. No data are available about another beta-blocker, nadolol, which, unlike propranolol, has a low hepatic metabolism, a low lipid solubility, a long serum half-life and does not reduce renal blood flow in patients with arterial hypertension. In 18 cirrhotics with portal hypertension, the effects of nadolol were studied on systemic and hepatic haemodynamics and liver function, at a dosage which reduced the heart rate by 25%. After one month of treatment, a significant decrease in cardiac output, portohepatic gradient and estimated hepatic blood flow were found. The degree of oesophageal varices was reduced in 11 patients, unchanged in the other seven. Hepatic function, evaluated by galactose eliminating capacity, did not change significantly. Although the small number of treated patients does not allow definitive conclusions, nadolol seems to have the features needed to be used in the medical treatment of portal hypertension in patients with liver cirrhosis.

Cardiac Output↗

[Effect of somatostatin on splanchnic hemodynamics in liver cirrhosis].

The effect of somatostatin on splanchnic haemodynamics in patients with liver cirrhosis is not clearly defined, as some Authors reported a decrease in portal pressure and in liver blood flow during i.v. administration of this hormone, while others did not. In 19 subjects with liver cirrhosis and portal hypertension the following parameters were measured before and during i.v. infusion of somatostatin (7.5 micrograms/min): porto-hepatic gradient, effective hepatic plasma flow, specific splenic blood flow, cardiac output. Moreover the gastrin-G-17 plasma levels, those of insulin and growth hormone were measured. Effective hepatic plasma flow decreased significantly during somatostatin infusion (P less than 0.05), averaging a 15% decrease. Porto-hepatic gradient, specific splenic blood flow, cardiac output did not vary significantly. Gastrin, insulin and growth hormone plasma levels decreased significantly (P less than 0.02, 0.01, 0.05). These data indicate that somatostatin infused at the dose of 7.5 micrograms/min provokes endocrine effects, but as far as the splanchnic circulation is concerned, it induces a slight decrease in liver blood flow without affecting portal hypertension.

Adult↗

Effects of nadolol treatment on renal and hepatic hemodynamics and function in cirrhotic patients with portal hypertension.

Twelve cirrhotic patients with portal hypertension and esophageal varices were treated with nadolol for 1 month, and the effects on renal and hepatic hemodynamics and function were studied. A significant decrease in cardiac output, portohepatic gradient, and effective hepatic blood flow was found, whereas mean arterial pressure, liver function, effective renal blood flow, glomerular filtration rate, and urinary sodium and potassium excretions were not affected. In seven patients esophageal varices were also reduced. A significant correlation was found between the decrease in portohepatic gradient and that in cardiac output. The percentage of cardiac output distributed to the kidneys was significantly increased after nadolol treatment. In conclusion, nadolol seems to have properties useful for the treatment of portal hypertension in patients with liver cirrhosis.

Adrenergic beta-Antagonists↗

Carbohydrate and lipid metabolism in cirrhosis. Evidence that hepatic uptake of gluconeogenic precursors and of free fatty acids depends on effective hepatic flow.

Splanchnic arteriovenous differences for several intermediary metabolites of carbohydrate and lipid metabolism were determined simultaneously with hepatic blood flow in seven normal subjects, eight patients with cirrhosis, and six patients with cirrhosis after surgical portosystemic shunt ( SPSS ) after an overnight fast. Arteriovenous differences in the legs were also determined together with flux measurement. The individual turnover rates of acetoacetate (AcAc) and 3 hydroxybutyrate (beta OHB) were also determined by means of isotopic techniques. Splanchnic gluconeogenic precursors and FFA uptakes were lower in cirrhotic patients with SPSS than in normal subjects (P less than 0.05 and P less than 0.01, respectively). Splanchnic triglyceride output was also lower in cirrhotic patients with SPSS than in normal subjects (P less than 0.01), whereas no significant differences were found for AcAc, beta OHB, and glucose release. In the group of cirrhotic patients without SPSS , those patients with negligible signs of portal systemic shunt and normal splanchnic blood flow had uptake of gluconeogenic precursors and of FFA normal or higher than that of normal subjects, whereas those patients with signs of spontaneous portal systemic shunt behaved like cirrhotic patients with SPSS . Alanine release from the leg was lower in both cirrhotic patient groups. Tracer determined hepatic output of AcAc and beta OHB was higher in cirrhotic patients with SPSS (P less than 0.05). Plasma clearance rates of AcAc and beta OHB were significantly elevated in both cirrhotic patient groups. Close agreement was found between tracer and catheterization techniques in the evaluation of ketone body production in cirrhotic patients with SPSS , whereas in cirrhotic patients without SPSS tracer determined hepatic output was slightly lower, possibly because of extrahepatic splanchnic tissue ketone body uptake. In conclusion, our data in patients with cirrhosis indicate that: 1) splanchnic uptake of gluconeogenic precursors and of FFA was related to the degree of portal systemic shunt, e.g. to the degree of effective hepatic blood flow; 2) liver triglyceride but not ketone body output was decreased by the impaired FFA (and glycerol) liver uptake; 3) the higher circulating levels of gluconeogenic precursors (except alanine) and of FFA appeared at least partially due to lower hepatic removal of these metabolites; and 4) peripheral use of ketone bodies was increased and alanine release from the leg reduced in patients with cirrhosis.

Adult↗

Beta 2-microglobulin concentration in plasma and production in liver cirrhosis.

The beta 2-microglobulin plasma level is often high in patients suffering from cirrhosis. Many authors believe this to be due to an increased production, provided that the creatinine level is in the normal range. In the present study, alterations in the plasma level and production of beta 2-microglobulin were investigated in patients with liver cirrhosis without overt renal failure. 62 patients, 48 men and 14 women, suffering from liver cirrhosis were examined. The glomerular filtration rate (GFR) and plasma beta 2-microglobulin were measured in all patients and in 16 controls. As beta 2-microglobulin is freely filtered by glomeruli and its extrarenal catabolism is negligible, the beta 2-microglobulin filtration rate was calculated as the product of the beta 2-microglobulin plasma level times the GFR. In steady state conditions, the beta 2-microglobulin filtration rate may be used as an indirect index of beta 2-microglobulin production. The beta 2-microglobulin plasma level was high in 26 patients; however, only 12 of them showed a definite rise in beta 2-microglobulin production, as shown by an increased beta 2-microglobulin filtration rate. The 14 patients with high beta 2-microglobulin plasma levels without high beta 2-microglobulin filtration rates obviously showed a decreased GFR; however, creatinine was not increased because of its small sensitivity as an index of renal function. A linear correlation was found between IgG and the beta 2-microglobulin filtration rate (r = 052; p less than 0.02), not between IgG and the beta 2-microglobulin plasma level. The other indices of liver damage were not related to the beta 2-microglobulin filtration rate of plasma level.

Female↗

Renal effects of aminophylline in hepatic cirrhosis.

In 18 cirrhotics with impaired renal perfusion intravenous injection of aminophylline 3 mg/kg b.w. increased mean renal blood flow (133-Xenon washout) from 1.77 +/- 0.71 to 1.99 +/- 0.44 ml/g/min (p less than 0.01). No significant change in cardiac output was found. In a further 10 cirrhotic patients the administration of aminophylline 3 mg/kg decreased the mean tubular reabsorption of sodium in the proximal section of the nephron (distal delivery) from 10.5 +/- 6.2 to 16.3 +/- 16.5 (p less than 0.01). Free-water production increased as a consequence of the increased supply of sodium to the diluting segment. Thus, aminophylline acts favourably on the functional renal impairment that occurs in hepatic cirrhosis.

Adult↗

Pathogenetic relationships between renal tubular acidosis and sodium metabolism alterations in liver cirrhosis.

5 cirrhotic patients with latent distal renal tubular acidosis (RTA) and 5 cirrhotic patients with normal distal acidification ability were studied. All the patients were maintained on a 80 mEq/day sodium diet for at least 5 days before the study. Only 2 of the 5 patients with RTA showed a reduced daily sodium excretion while the 3 other patients with RTA had a normal natriuresis. Acidification ability was retested in all the patients after increasing sodium distal delivery by intravenous administration of ethacrynic acid. Some hours after the maximal natriuretic effect induced by ethacrynic acid, a normalization of the acidification test was seen in all patients with RTA. These findings support the concept that although sodium metabolism alterations are not the only factor in the pathogenesis of RTA in liver cirrhosis, reduced availability of sodium at the distal tubule may impair tubular acidification, probably by influencing the distal transtubular potential difference.

Acidosis, Renal Tubular↗

Relationship between plasma levels of factor VIII related antigen and reticulo-endothelial function in chronic uremia.

The plasma levels of factor VIII related antigen (F VIIIR:Ag; determined by rocket electrophoresis) and reticulo-endothelial function (measured by means of the removal kinetics of human albumin millimicrospheres) were studied in a group of patients with chronic renal failure. F VIIIR:Ag plasma levels were increased, median 304% (interquartile ranges 211-443%) compared to the controls, median 112% (interquartile ranges 100-144%); P less than 0.01. Reticulo-endothelial function was decreased, median 8.3 micrograms/min/kg body wt (interquartile ranges 6.2-10.1 micrograms/min/kg body wt) compared to the controls, median 15.0 micrograms/min/kg body wt (interquartile ranges 11.9-19.0 micrograms/min/kg body wt); P less than 0.02. A significant inverse relationship was found between plasma levels of F VIIIR:Ag and the reticulo-endothelial function rs = 0.075; P less than 0.01). As the main site of catabolism of F VIIIR:Ag is the reticulo-endothelial system, the impairment of its function appears to be a possible explanation for the elevated plasma levels of the F VIIIR:Ag found in patients with end stage renal disease.

Adult↗

Effects of captopril on renal function in hypertensive patients.

The effects of captopril (SQ 14225) on renal function were studied in 10 hypertensive patients. After 7 weeks of treatment (75 to 500 mg/day) renal plasma flow was practically unchanged and glomerular filtration rate was only slightly decreased despite a significant decrease in blood pressure. All indexes of glomerular capillary permeability and of tubular anatomic integrity remained normal during the treatment period.

Adult↗