Prognostic value of hepatic venous pressure gradient measurements in alcoholic cirrhosis: a 10-year prospective study.

BACKGROUND & AIMS: Different parameters are considered predictors of bleeding and death in alcoholic cirrhosis. The aim of this study was to establish the prognostic value of a prospective and sequential evaluation of portal pressure, variceal size, and Pugh's score in portal-hypertensive patients with alcoholic cirrhosis but no previous bleeding. METHODS: Thirty patients were evaluated for 42 +/- 5 months (median, 39 months). After baseline studies, 30 patients underwent an additional evaluation (follow-up 1; median, 10 months), 20 patients a second evaluation (follow-up 2; median, 25 months), and 13 patients a third evaluation (follow-up 3; median, 45 months). No prophylactic treatment for bleeding was given. End points were bleeding and/or death. RESULTS: Seventeen patients died, and 10 patients bled. At follow-up 1, portal pressure decreased both in survivors and nonbleeders (from 18.7 +/- 1.0 to 15.2 +/- 1.3 mm Hg [P < 0.01] and from 18.9 +/- 0.8 to 16.5 +/- 1.0 mm Hg [P < 0.05], respectively). On multivariate analysis (Cox model), portal pressure at follow-up 1 had the best prognostic and independent value for both bleeding and survival. Subsequent studies showed similar trends. CONCLUSIONS: Measurements of portal pressure provide unique prognostic information for predicting portal hypertensive-related bleeding and mortality in patients with alcoholic cirrhosis.

Propranolol compared with propranolol plus isosorbide dinitrate in portal-hypertensive patients: long-term hemodynamic and renal effects.

The long-term hemodynamic and renal effects of propranolol were compared with those of propranolol plus isosorbide dinitrate in 44 portal-hypertensive alcoholic cirrhotic patients. Eight control patients, 8 patients receiving propranolol and 14 patients receiving propranolol plus isosorbide dinitrate were hemodynamically evaluated. Renal function was studied in a fourth group of 14 patients receiving propranolol plus isosorbide dinitrate. Portal pressure decreased more (p < 0.05) with combined therapy (-21.6%, from 19.5 +/- 4.8 to 15.4 +/- 4.3 mm Hg) than with propranolol alone (-12.5%, from 19.9 +/- 1.2 to 17.4 +/- 1.8 mm Hg). Serum urea and creatinine levels, plasma sodium concentration, urine volume and urinary sodium excretion showed nonsignificant changes in all groups studied. Combined therapy induced a significant (p < 0.05) decrease in plasma renin activity (from 4.42 +/- 4.7 to 1.59 +/- 1.9 ng/ml/hr) and nonsignificant reductions in plasma aldosterone concentration and creatinine clearance. None of the eight patients with ascites or history of ascites not receiving isosorbide dinitrate showed evidence of impairment in renal sodium metabolism during the study period. In contrast, 8 of the 14 patients (57%) with ascites or history of ascites receiving isosorbide dinitrate showed impairment in renal sodium metabolism (p < 0.01), as reflected by the development or worsening of ascites and the need of higher diuretic requirements. Long-term combined administration of propranolol plus isosorbide dinitrate is superior to propranolol alone in the pharmacological treatment of portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term hemodynamic effects of ketanserin, a 5-hydroxytryptamine blocker, in portal hypertensive patients.

Ketanserin, a 5-hydroxytryptamine-2 receptor blocker, has been shown to decrease portal pressure in recent acute hemodynamic studies that have been performed both in experimental animals and portal hypertensive patients. The present study was designed to investigate the effects of chronic oral administration of ketanserin in portal hypertensive patients with cirrhosis. The mean baseline hepatic venous pressure gradient in the 13 patients with alcoholic cirrhosis who completed the study was 15.7 +/- 2.7 mmHg. It decreased significantly to 13.3 +/- 2.0 mmHg (p less than 0.001) after ketanserin was administered at a mean dose of 51 mg per day for a mean period of 32 days. This 14.6% reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure (from 22.2 +/- 4.0 to 20.1 +/- 3.6 mmHg) and was accompanied by significant decreases in cardiac index (18.8%) and in mean arterial pressure (8.1%). However, changes in cardiac index or in mean arterial pressure were not predictive of modifications in the hepatic venous pressure gradient. Eight of 16 patients entered in the study developed side effects, the most significant being a reversible portosystemic encephalopathy, which occurred in three patients who had poor liver function. This study confirms evidence in favor of a role for 5-hydroxytryptamine in portal hypertension and adds a new group of agents for the chronic treatment of portal hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute and chronic hemodynamic effects of propranolol in unselected cirrhotic patients.

Different and contradictory results concerning the use of propranolol in the treatment of portal hypertension have been reported. This study was designed to investigate the hemodynamic effects of short- and long-term administration of propranolol in portal hypertensive patients. Portal pressure, cardiac index, heart rate and blood pressure were obtained in 18 unselected alcoholic cirrhotic patients with esophageal varices before and 60 min after the oral administration of 40 mg propranolol and again after 106 +/- 35 days of continuous oral administration (mean dose = 158 +/- 63 mg per day). Baseline portal pressure was 21.7 +/- 7.2 mm Hg. It decreased after 60 min to 17.2 +/- 5.5 mm Hg (p less than 0.01) and after long-term administration of propranolol to 16.1 +/- 5.7 mm Hg (p less than 0.01). No decrease in portal pressure was noted in 9 of 18 (50%) patients after acute administration and 5 of 17 (30%) patients after long-term administration. Baseline cardiac index was 5.1 +/- 1.2 liters X min-1 X m-2. It decreased after 60 min to 3.9 +/- 1.4 liters X min-1 X m-2 (p less than 0.01) and to 3.6 +/- 1.0 liters X min-1 X m-2 after long-term administration (p less than 0.001). Baseline heart rate was 85 +/- 11 beats per min. It decreased after 60 min to 75 +/- 9 (p less than 0.001) and after long-term administration to 62 +/- 6 (p less than 0.001) beats per min. Baseline mean arterial pressure was 108 +/- 11 Hg. It decreased after 60 min to 97 +/- 14 mm Hg (p less than 0.01) and after long-term administration to 103 +/- 14 mm Hg (not statistically significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased blood flow through the portal system in cirrhotic rats.

Portal venous pressure is the result of the interplay between portal venous blood flow and the vascular resistance offered to that flow. Whether portal hypertension is maintained only by an increased portal venous resistance or also by an increased blood flow within the portal venous system is still open to speculation. To resolve these differences, splanchnic and systemic hemodynamics were evaluated in cirrhotic rats, induced by CCl4. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. All cirrhotic rats had portal hypertension (portal venous pressure 13.5 +/- 1.1 vs. 9.0 +/- 0.5 mmHg, in normal control rats; p less than 0.01), but portal-systemic shunting in cirrhosis (31% +/- 13% vs. 0.2% +/- 0.02%; p less than 0.05) was variable, ranging from 1% to 97%. Portal venous inflow, the total blood flow within the portal system, was increased in cirrhotic rats (5.75 +/- 0.04 vs. 4.52 +/- 0.36 ml/min per 100 g; p less than 0.05). Total splanchnic arterial resistance was reduced in cirrhotic rats (3.3 +/- 0.2 vs. 5.8 +/- 0.5 dyn X s X cm-5 X 10(5); p less than 0.01). Portal venous resistance, however, was not abnormally elevated in cirrhotic rats (4.6 +/- 0.5 vs. 4.7 +/- 0.5 dyn X s X cm-5 X 10(4), p = NS). Splanchnic hemodynamics in cirrhotic rats demonstrate that portal hypertension is maintained, at least in part, by a hyperdynamic portal venous inflow. The hemodynamic data in cirrhotic rats provided evidence that supports the role of an increased portal blood flow in portal hypertension and gives a quantitative definition of splanchnic hemodynamics in intrahepatic portal hypertension.

[Determination of hepatic blood flow in chronic liver diseases using the constant infusion technic]. / Determinación del flujo sanguíneo hepático en hepatopatías crónicas con técnica de infusión contínua.

Hepatic blood flow was measured in 10 cirrhotic patients by a constant infusion of Indocyanine Green (ICG) and details of the technique are analysed. A decrease in total hepatic blood flow (0.777 +/- 0.38 l/min.) was found in most of the patients. Different variations in hepatic blood flow were observed in three patients after the administration of Cimetidine (300 mg IV). The response in hepatic blood flow in another patient in whom a peritoneo-jugular valve (Le Veen shunt) was inserted in analysed.

Determinacion del flujo sanguineo hepatico en hepatopatias cronicas con tecnica de infusion continua. / Determination of hepatic blood flow in chronic liver diseases by constant infusion technic

La determinacion del flujo sanguineo hepatico fue efectuada en pacientes portadores de hepatopatia cronica. Se utilizo um metodo de infusion continua con verde de indocianina, cuya tecnica se detalla.Los resultados basales en 10 pacientes y ejemplos de aplicacion de la tecnica son analizados. La correlacion del flujo sanguineo hepatico con otros elementos contribuye a definir de mejor manera el perfil hemodimico de las hepatopatias cronicas

Determinación del flujo sanguíneo hepático en hepatopatías crónicas con técnica de infusión contínua. / [Determination of hepatic blood flow in chronic liver diseases using the constant infusion technic]

Hepatic blood flow was measured in 10 cirrhotic patients by a constant infusion of Indocyanine Green (ICG) and details of the technique are analysed. A decrease in total hepatic blood flow (0.777 +/- 0.38 l/min.) was found in most of the patients. Different variations in hepatic blood flow were observed in three patients after the administration of Cimetidine (300 mg IV). The response in hepatic blood flow in another patient in whom a peritoneo-jugular valve (Le Veen shunt) was inserted in analysed.

Determinacion del flujo sanguineo hepatico en hepatopatias cronicas con tecnica de infusion continua. / Determination of hepatic blood flow in chronic liver diseases by constant infusion technic

La determinacion del flujo sanguineo hepatico fue efectuada en pacientes portadores de hepatopatia cronica. Se utilizo um metodo de infusion continua con verde de indocianina, cuya tecnica se detalla.Los resultados basales en 10 pacientes y ejemplos de aplicacion de la tecnica son analizados. La correlacion del flujo sanguineo hepatico con otros elementos contribuye a definir de mejor manera el perfil hemodimico de las hepatopatias cronicas

Hyperdynamic circulation in portal-hypertensive rat model: a primary factor for maintenance of chronic portal hypertension.

Two dissimilar hemodynamic hypotheses, the "backward flow" theory and the "forward flow" theory, have been advanced to define splanchnic hemodynamics in portal hypertension. An animal model with portal hypertension and high-grade portal-systemic shunting, the portal vein-stenotic rat, was studied to determine whether a hemodynamic picture compatible with either theory would develop. Splanchnic and systemic hemodynamics and portal-systemic shunting were measured by radioactive microsphere techniques. The portal-hypertensive rats (portal pressure, 12.8 +/- 0.5 vs. 8.3 +/- 0.4 mmHg) with greater than 95% portal-systemic shunting had a 60% increase in portal venous inflow (23.46 +/- 2.54 vs. 14.97 +/- 1.61 ml/min; P less than 0.01) with a concomitant 50% decrease in splanchnic arteriolar resistance (3.86 +/- 0.43 vs. 7.60 +/- 0.80 dyn . s . cm-5 . 10(5); P less than 0.001) compared with control rats. Cardiac index (391 +/- 17 vs. 250 +/- 20 ml . min-1 . kg-1) was elevated 50% (P less than 0.001), and total peripheral resistance (7.1 +/- 0.4 vs. 11.7 +/- 0.8 dyn . s . cm-5 . 10(4)) was decreased 60% (P less than 0.001). The resistance to portal blood flow in portal vein-stenotic rats (4.77 +/- 0.57 dyn . s . cm-5 . 10(4)) was similar to the resistance to portal blood flow in control rats (4.82 +/- 0.43 dyn . s . cm-5 . 10(4)), indicating that the hyperdynamic portal venous inflow, not resistance, provided the main impetus for maintaining the elevated portal venous pressure. The splanchnic hemodynamic observations directly support the forward flow theory of portal hypertension. The relation between splanchnic arteriolar resistance and total peripheral resistance (r = 0.67; P less than 0.01) indicated that the systemic hemodynamic parameters were secondarily altered by the splanchnic hemodynamic changes. This animal model of chronic portal hypertension gave evidence for a generalized splanchnic arteriolar vasodilation occurring in the presence of high-grade portal-systemic shunting.

Splanchnic hemodynamics in portal-hypertensive rats: measurement with gamma-labeled microspheres.

A method to quantitate hepatic arterial flow (HA), portal venous flow (PBF), and blood flow through portal-systemic shunts (ShBF) in portal-hypertensive rats is described. This method relies on the injection of two differently radiolabeled microspheres (15 micrometers) into the left ventricle and spleen. To evaluate the usefulness of this technique, studies were performed on normal, cirrhotic, and portal vein-ligated rats anesthetized with ketamine. With this method, PBF is calculated indirectly from the sums of the blood flow of the splanchnic organs that drain into the portal vein. In the portal-hypertensive animals with portal-systemic shunting, this technique allows for the determination of PBF perfusing the liver [hepatic fraction of portal flow (HFP)] and PBF escaping through portal-systemic shunts (ShBF). The portal vein-ligated rats have higher HA flow (0.68 +/- 0.08 ml . min-1 . g-1) and lower HFP (0.08 +/- 0.01 ml . min-1 . g-1) than either the cirrhotic (HA: 0.27 +/- 0.03 ml . min-1 . g-1, P less than 0.01; HFP: 1.20 +/- 0.20 ml . min-1 . g-1, P less than 0.01) or the normal rat (HA: 0.29 +/- 0.06 ml . min-1 . g-1, P less than 0.01; HFP: 1.39 +/- 0.16 ml . min-1 . g-1, P less than 0.01). No significant difference was found between the cirrhotic and normal rats. The ShBF was higher in the portal vein-ligated rats (21.4 +/- 2.8 ml/min) than in the cirrhotic (4.6 +/- 2.5 ml/min, P less than 0.001) or normal rats (0.03 +/- 0.005 ml/min, P less than 0.01). The difference between the cirrhotic and normal animals was also significant (P less than 0.05). This is a simple, rapid, and reliable technique that allows for the quantitation of splanchnic hemodynamics in experimental models with portal hypertension.

[Intrahemorrhagic esophagogastroduodenofibroscopy. Survey in the city of Rosario]. / Esofagogastroduodenofibroscopias intrahemorrágicas. Encuesta en la ciudad de Rosario.

1.897 patients with upper gastrointestinal bleeding (UGIB) were studied and the cause was diagnosed in 1.756 (92.6%). The most frequently found pathology was the acute bleeding gastropathy (24.5%). Considering the gastric duodenal and anastomotic ulcer as a whole, in 47.5% of the cases the ulcer was observed. Both pathologies together make out that 72 out of 100 patients with UGIB have bleeding due to an ulcer or gastritis. It comes out that the low incidence of neoplasy as a consequence of UGIB and that the 31% of the diagnosed pathology could not have been diagnosed by X-ray.