This study was designed to investigate whether the addition of nitroglycerin to vasopressin infusion could avoid the deleterious systemic effects of vasopressin while maintaining or enhancing the therapeutic benefits of portal pressure reduction. The effect of nitroglycerin on splanchnic and systemic hemodynamics was studied in cirrhotic patients and portal hypertensive dogs receiving i.v. vasopressin. During i.v vasopressin infusion (0.4 units per min), the cardiac output decreased in patients by 14% from 7.6 +/- 0.9 (mean +/- S.E.) to 6.5 +/- 0.7 liters per min, p less than 0.01, the mean arterial pressure increased 21% from 87 +/- 2 to 105 +/- 4, p less than 0.01, and the heart rate decreased 11% from 79 +/- 3 to 71 +/- 3, p less than 0.01. The administration of sublingual nitroglycerin (0.4 mg) returned all the systemic hemodynamic parameters to baseline values. In dogs, vasopressin infusion significantly reduced portal pressure and flow while increasing portal venous resistance. Nitroglycerin when added to the vasopressin infusion reduced portal venous resistance and further decreased portal pressure in dogs. In patients, vasopressin reduced the hepatic blood flow (44%), wedged hepatic venous pressure (11%), and the gradient between wedged and free hepatic venous pressures (23%). Nitroglycerin administration caused a further reduction of the wedged hepatic venous pressure (23.6 +/- 2.3 to 21.1 +/- 2.0, 11%, p less than 0.01). There was a small but not significant further decline (7%) in the hepatic venous pressure gradient. These results provide evidence that the addition of nitroglycerin to an i.v. infusion of vasopressin reversed the detrimental effects of vasopressin while preserving the beneficial effects.

Animals↗

PubMedDate not supplied

Splanchnic and hepatic metabolism of somatostatin: a study in cirrhotic patients with a portacaval shunt.

Experimental data suggest that somatostatin is metabolized by both liver and kidneys. Results in humans are conflicting. By studying a group of cirrhotic patients with surgically induced end-to-side portacaval shunts, basally and during a somatostatin infusion, we have been able to analyze separately the hepatic and splanchnic metabolism of this peptide. After catheterization, samples were obtained from the pulmonary artery, portal and hepatic veins. Basal pulmonary artery immunoreactive somatostatin (IRS) was significantly higher (p less than 0.001) in the cirrhotic patients (96 +/- 11 pg per ml) than in a sex- and age-matched control group (31.4 +/- 5.8 pg per ml). During the infusion of exogenous somatostatin, IRS values were higher in arterial (12,269 +/- 1,198 pg per ml) than in hepatic venous blood (7,648 +/- 1,234 pg per ml), indicating hepatic extraction of the peptide; but there was also a substantial splanchnic extraction demonstrated by higher arterial (12,269 +/- 1,532 pg per ml) than portal values (6,754 +/- 1,040 pg per ml) of IRS. During the somatostatin infusion, at very high circulation IRS levels, the liver was able to extract 38% of the peptide. This suggests that the high basal IRS levels found in liver cirrhosis are not likely to be due to hepatic failure. Possible mechanisms may involve increased somatostatin secretion, predominance of high molecular weight moieties of IRS which may not be as effectively removed by the liver, and/or portal-systemic shunting.

Adult↗

PubMedDate not supplied

Chronic bile duct ligation in the dog: hemodynamic characterization of a portal hypertensive model.

Splanchnic and systemic hemodynamics were measured in six normal dogs and in 18 dogs that had the bile ducts ligated for a period of 8 weeks. In the bile duct-ligated dogs, there was a decrease in arterial pressure (110 +/- 4 mm Hg vs. normal 136 +/- 6 mm Hg; p less than 0.005) and peripheral vascular resistance (4.60 +/- 0.38 vs. 6.28 +/- 0.38 dynes-sec-cm-5; p less than 0.02), and an increase in cardiac index (129 +/- 7 vs. 98 +/- 9 ml per min per kg; p less than 0.05). The splanchnic hemodynamic characteristics in the bile duct-ligated dogs included an increase in portal venous pressure (13.3 +/- 0.6 mm Hg vs. 6.7 +/- 0.5 mm Hg; p less than 001) and wedged hepatic venous pressure (14 +/- 1.2 mm Hg), the development of extensive portal-systemic shunting (49 +/- 10 vs. 0.03 +/- 0.01%; p less than 0.01), and a decrease in portal venous flow (194 +/- 21 ml per min vs. 427 +/- 21 ml per min; p less than 0.001). This study demonstrated that chronic bile duct-ligated dogs develop sinusoidal portal hypertension with extensive portal-systemic shunting and a hyperdynamic systemic circulation. These findings closely resembled hemodynamic abnormalities observed in human cirrhosis and suggest that this model is useful in physiopathological and pharmacological studies of portal hypertension.

Animals↗

PubMedDate not supplied

Exudative ascites in the course of acute type B hepatitis.

Two patients who presented with an exudative ascites in the course of typical acute type B hepatitis are reported. In one of them, ascites was associated with an exudative pleural effusion. In both patients, the clinical course of the hepatitis was uneventful, and ascites and pleural effusion disappeared spontaneously. Portal hypertension and common causes of exudative ascites were excluded. It is suggested that the development of exudative ascites in these patients represent a hitherto unrecognized manifestation of the hepatitis itself.

Acute Disease↗

PubMedDate not supplied

Measurement of azygos venous blood flow by a continuous thermal dilution technique: an index of blood flow through gastroesophageal collaterals in cirrhosis.

A method to quantitate blood flow through the gastroesophageal collaterals in portal hypertensive patients was developed. Since gastroesophageal collaterals drain into the azygos system, it is postulated that measurement of blood flow in the azygos vein should provide a quantitative measurement of gastroesophageal collateral blood flow changes in portal hypertensive patients. Azygos blood flow was measured using a double thermodilution catheter directed under fluoroscopy to the azygos vein. Ten patients with alcoholic cirrhosis were studied. Five of these patients had a history of repeated bleeding from gastroesophageal varices (Group I). The azygos blood flow in these patients was 596 +/- 78 ml per min. The other five patients all had decompressive surgery of the portal system (Group II). In these patients the azygos venous blood flow was 305 +/- 29 ml per min (p less than 0.01). The coefficient of variation of repeated baseline measurements was of 4.4 +/- 0.6%. The azygos venous blood flow measurement is a rapid, simple and sensitive method to evaluate blood flow changes in the vessels involved in gastroesophageal bleeding due to portal hypertension.

Azygos Vein↗

PubMedDate not supplied

Comparison of intravenous somatostatin and vasopressin infusions in treatment of acute variceal hemorrhage.

The present trial compared the effectiveness and complications of intravenous somatostatin and vasopressin in treatment of variceal bleeding. Sixty-one cirrhotic patients with endoscopically proven active variceal bleeding were included. Both drugs were given as continuous intravenous infusions for 48 hr. Thirty patients received somatostatin (250 micrograms per hr after a bolus of 50 micrograms) and 31 vasopressin (0.4 units per min). Initial control of bleeding was achieved in 26 (87%) patients receiving somatostatin and in 23 (74%) of those treated with vasopressin. However, 10 patients [not significant statistically] in the somatostatin group and 5 in the vasopressin group rebled during treatment, after a mean of 15 and 20 hr, respectively. Therefore, complete control of bleeding during the 48 hr of therapy was achieved in 16 (53%) patients treated with somatostatin and in 18 (58%) of those receiving vasopressin. Mortality during hospitalization was similar in both groups (somatostatin 47%, vasopressin 45%). Differences were observed in complications associated with each therapy. Vasopressin produced major complications in 8 patients (left ventricular failure in 4 and severe abdominal pain requiring drug withdrawal in 4), and minor complications in 14; somatostatin infusion produced minor complications in 3 patients (p less than 0.01). In addition, the serum sodium concentration was significantly reduced by vasopressin (from 134.3 +/- 1.6 to 128.3 +/- 1.4 mEq per liter, p less than 0.001) but not by somatostatin (134.6 +/- 1.1 vs. 133.2 +/- 1.1 mEq per liter). This study shows that somatostatin is as effective as vasopressin in controlling variceal hemorrhage, but has a much lower rate of complications.

Esophageal and Gastric Varices↗