Azygos and hepatic extraction of atrial natriuretic factor (ANF) in patients with cirrhosis. No evidence of reduced disposal.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
F Bendtsen
Publications and source records attributed to F Bendtsen.
Disposal of atrial natriuretic factor (ANF99-126) in patients with cirrhosis: effect of beta-adrenergic blockade.
To test a possible effect of blood flow change on disposal of atrial natriuretic factor: ANF99-126 (ANF), we determined renal, azygos, hepatic and cubital venous, and arterial plasma concentrations of ANF in 18 patients with cirrhosis before and after ingestion of propranolol 80 mg. Arterial ANF was similar to that of controls (9.4 vs. 10.9 pmol l-1, NS) and was positively correlated to cardiac output (r = 0.49, p < 0.02) and to right atrial pressure (r = 0.44, p < 0.01). All the vascular beds examined extracted ANF significantly. The renal (n = 17), hepato-enteric (n = 16), and splanchnic superior collateral (azygos) beds (n = 13) had significantly higher extraction ratios (0.34-0.39) than that observed in the cubital vein (0.24, n = 15, p < 0.05). Arterial ANF showed no significant change (9.6-11.0 pmol l-1, NS) after reduction of cardiac output (-25%, p < 0.001) by propranolol. Only insignificant changes in ANF extraction and a small decrease in azygos and hepato-enteric clearance occurred during beta-adrenergic blockade. Our results show a substantial extraction of ANF in the kidney, in the splanchnic bed drained through superior portosystemic collaterals, and in the hepato-enteric bed. Only minor effects on ANF extraction were observed after reduction of the blood flow with propranolol.
Adult↗
Oesophageal varices prior to bleeding. Diagnosis and physiological and therapeutic effects of propranolol in cirrhosis.
Explore the source record for details and available documents.
Esophageal and Gastric Varices↗
Effect on hemodynamics of a liquid meal alone and in combination with propranolol in cirrhosis.
Thirteen patients with alcoholic cirrhosis had splanchnic and systemic hemodynamics assessed before and after ingestion of a standard liquid meal of 700 kcal (consisting of isocaloric proteins, lipids, and carbohydrates). Half of the patients (n = 6) were randomized to a treatment group receiving intravenous infusion of propranolol in combination with the meal. No significant effects were observed on systemic hemodynamics after the meal alone. Heart rate (-14%; P less than 0.01) and cardiac index (-24%; P less than 0.01) decreased after meal in combination with propranolol. The mean hepatic venous pressure gradient increased significantly after ingestion of the meal alone with a maximal effect after 30 minutes (+13%; P less than 0.05) and returned to baseline values after 2 hours. Meal in combination with propranolol had no significant effect on the hepatic venous pressure gradient. Hepatic blood flow increased substantially after the meal alone with a maximal effect after 30 minutes (+28%; P less than 0.01), whereas no significant effect was observed after meal in combination with propranolol. Azygos blood flow increased significantly after the meal alone (+36%; P less than 0.05), whereas this effect was abolished in combination with propranolol. In conclusion, ingestion of a peroral mixed meal in cirrhotic patients has, contrary to what is observed in normal controls, no effects on systemic hemodynamics. Substantial changes in splanchnic hemodynamics were observed, and these effects were all abolished when the meal was administered in combination with propranolol.
Analysis of Variance↗
Estimated central blood volume in cirrhosis: relationship to sympathetic nervous activity, beta-adrenergic blockade and atrial natriuretic factor.
The estimated central blood volume (i.e., blood volume in the heart cavities, lungs and central arterial tree) was determined by multiplying cardiac output by circulatory mean transit time in 19 patients with cirrhosis and compared with sympathetic nervous activity and circulating level of atrial natriuretic factor. Arterial norepinephrine level, an index of overall sympathetic nervous activity (3.08 nmol/L in patients vs. 1.36 nmol/L in controls; p < 0.01) was negatively correlated (r = -0.54, p < 0.01) with estimated central blood volume (mean = 23 ml/kg in patients vs. 27 ml/kg in controls; p < 0.05). Similarly, renal venous norepinephrine level (an index of renal sympathetic tone; 4.26 nmol/L in patients vs. 1.78 nmol/L in controls; p < 0.01) was inversely correlated with estimated central blood volume (r = -0.53, n = 18, p < 0.02). No significant correlation could be established between arterial atrial natriuretic factor level (8.9 pmol/L in patients vs. 9.6 pmol/L in controls; not significant) and estimated central blood volume. Hemodynamic values were subsequently modified with oral propranolol (80 mg). During beta-adrenergic blockade, the mean estimated central blood volume was not altered significantly, except in six patients who exhibited decreases in mean arterial blood pressure (85 to 69 mm Hg; n = 6) and decreases in mean estimated central blood volume (23.2 to 20.6 ml/kg; n = 6, p < 0.05). Slight increases were observed in mean right atrial pressure (2.2 to 3.7 mm Hg; n = 14, p < 0.05); this change was positively correlated with the change in estimated central blood volume (r = 0.44, n = 14, p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗
Propranolol and haemodynamic response in cirrhosis.
In the present study, we compared cirrhotic patients who had a decrease in the hepatic venous pressure gradient after propranolol intake to patients without a decrease. Twenty patients with cirrhosis and oesophageal varices were investigated during hepatic vein catheterization before and 90 min after an oral dose of 80 mg propranolol. The hepatic venous pressure gradient decreased by 12.6% (19.0 +/- 4.7 to 16.3 +/- 3.6 mm Hg, p less than 0.05). Eight (40%) out of 20 patients had a decrease of less than 10% in protal pressure (non-responders). Responders had a higher baseline cardiac index than non-responders (3.79 +/- 0.74 vs. 2.83 +/- 0.53 1.min-1.m-2; p less than 0.01). No difference in the effect of propranolol on portal pressure was observed between patients with or without ascites, or between Child-Turcotte A, B, and C class patients. Our results suggest that cirrhotic patients who respond to oral propranolol with a decrease in portal pressure are more hyperdynamic than those without a significant fall in portal pressure.
Blood Pressure↗
Increased circulating calcitonin gene-related peptide (CGRP) in cirrhosis.
The etiology of the hyperkinetic circulatory state in cirrhosis is equivocal and reduced peripheral vascular resistance is a major unsolved problem in hepatic pathophysiology. It is therefore sensible to search for vasodilators. A recently discovered neuropeptide, calcitonin gene-related peptide (CGRP), is a highly potent vasodilator. We determined the circulating concentration of immunoreactive CGRP in different vascular beds in 35 patients with cirrhosis and in eight patients with minor disorders. Plasma CGRP was significantly increased in the cirrhotic patients compared with patients with minor disorders (59 vs. 46 pmol/l, p less than 0.01), as well as with 232 healthy persons (37 pmol/l, p less than 0.0001). Moreover, circulating CGRP increased significantly with the severity of cirrhosis (Child-Turcotte group A, 56; group B, 59; group C, 71 pmol/l; p less than 0.025). No significant arterio-venous net extraction or release of CGRP was found across the hepato-intestinal system, kidney, lung or limb. In conclusion, elevated circulating CGRP may play a role in the haemodynamic derangement of cirrhosis. The lack of organ arterio-venous differences suggests a widespread release and degradation of CGRP in many tissues and gives no evidence of decreased degradation as the cause of increased plasma CGRP in patients with cirrhosis.
Adult↗
Long-term effects of oral propranolol on splanchnic and systemic haemodynamics in patients with cirrhosis and oesophageal varices.
Splanchnic and systemic haemodynamics were measured in 24 patients with cirrhosis and oesophageal varices and no previous bleeding. The patients were randomized either to long-term treatment with propranolol (14 patients) or no active treatment (controls, 10 patients). Catheterization was performed again 1 year after randomization. After 1 year of treatment the hepatic venous pressure gradient had decreased in both the propranolol and control group (-16% versus -24% (NS), respectively). Hepatic blood flow decreased substantially in both groups but significantly more in the propranolol group (-39% versus -17% (p less than 0.05), respectively). Azygos blood flow was significantly reduced after 1 year in the propranolol group (-47%, n = 5 (p less than 0.05)), and no obvious effect was observed in the control group (-2%, n = 4). The cardiac index decreased significantly in the propranolol group but not in the control group (-20% versus -1% (p less than 0.05), respectively). Our results demonstrate that the splanchnic hyperdynamic condition observed in cirrhosis is in some of the patients partly reversible without pharmacologic treatment. No additional effect of propranolol was observed on portal pressure after 1 year of treatment with propranolol, whereas a decrease in azygos blood flow was observed only in the propranolol group. The beneficial effect of propranolol on the risk of bleeding from oesophageal varices may, therefore, mostly be due to a selective decrease in collateral blood flow and thereby variceal blood flow.
Administration, Oral↗
Effect of oral propranolol administration on azygos, renal and hepatic uptake and output of catecholamines in cirrhosis.
Circulating catecholamines are increased in cirrhosis with portal hypertension, and increase further after propranolol. In 23 cirrhotic patients, plasma norepinephrine and epinephrine were determined in an artery, the azygos vein, the right renal vein and a hepatic vein before and after an oral 80-mg dose of propranolol. Baseline azygos and renal venous norepinephrine levels were significantly higher than arterial norepinephrine levels (+20%, p less than 0.005; and +28%, p less than 0.001, respectively). Hepatic venous norepinephrine and all venous epinephrine values were below the arterial values (all p less than 0.05). After propranolol intake, arterial norepinephrine and epinephrine increased (+16%, p less than 0.01; and +93%, p less than 0.001, respectively). Significant increases in norepinephrine and epinephrine were found in azygos and renal veins (all p less than 0.01), whereas hepatic venous norepinephrine and epinephrine remained unchanged. Azygos and hepatic blood flow decreased after propranolol intake (-27%, p less than 0.05; and -16%, p less than 0.01, respectively). Azygos spillover of norepinephrine (an estimate of locally released norepinephrine delivered to the circulation) and clearance of epinephrine remained unaltered. Hepatointestinal clearance showed no significant change for norepinephrine, but showed a borderline-significant decrease for epinephrine (-23%, p = 0.08). Our results show a net production of norepinephrine in the prehepatic splanchnic area drained through superior portalsystemic collaterals and in the kidneys. The increase in circulating catecholamines after propranolol intake is probably due to a combination of further enhancement of sympathetic activity and a decrease in catecholamine degradation.
Administration, Oral↗
Serum levels of short-chain fatty acids in cirrhosis and hepatic coma.
Short-chain fatty acids cause reversible coma in animals and may contribute to the pathogenesis of the hepatic coma in humans. The concentrations of short-chain fatty acids in peripheral venous blood were significantly elevated in 15 patients with hepatic encephalopathy caused by cirrhosis (362 +/- 83 mumol/L; mean +/- S.E.M.) compared with 17 cirrhotic patients without encephalopathy (178 +/- 57 mumol/L) and 11 normal individuals (60 +/- 8 mumol/L). However, no correlation between the depth of coma and the level of short-chain fatty acids was found after repetitive measurements in the coma group. Compared with normal individuals, all short-chain fatty acids, except valerate, were elevated in patients with hepatic encephalopathy, whereas only the concentrations of isobutyrate and isovalerate were significantly elevated in cirrhotic patients without encephalopathy. The concentrations of short-chain fatty acids in 21 nonencephalopathic cirrhotic patients who underwent catheterization were equally distributed in the aorta (187 +/- 56 mumol/L), the hepatic vein (212 +/- 75 mumol/L), the azygos vein (140 +/- 37 mumol/L) and the renal vein (135 +/- 43 mumol/L) compared with peripheral venous blood (178 +/- 57 mumol/L). This study does not support the idea that short-chain fatty acids are of major importance in the pathogenesis of hepatic coma in patients with cirrhosis.
Adult↗
There is room for diminished central and arterial blood volume in cirrhosis.
Explore the source record for details and available documents.
Arteries↗
Agreement among multiple observers on endoscopic diagnosis of esophageal varices before bleeding.
The interobserver variation in diagnosis and grading of esophageal varices may be ascribed by characteristics of the observers as well as to the patients. Assessment of this variation therefore requires the contributions of multiple observers and patients. Twenty-eight patients with cirrhosis without previous bleeding or known presence of varices were subjected to upper gastrointestinal endoscopy. Each endoscopy was videotaped and shown to 22 endoscopists. The varices were graded on a scale of 0 to 3 according to size. Each endoscopist diagnosed varices in 8 to 20 patients (mean = 15.9). Overall agreement on the presence (grades 1 to 3) or absence (grade 0) of varices was 70%. The average kappa value was 0.38 (standard deviation = 0.16). Discrimination between varices graded 0 to 1 and varices graded 2 to 3 gave a higher kappa value (p less than 0.01) of 0.52 (standard deviation = 0.17). There was a large variation in kappa values (range = -0.025 to 0.975). No significant correlation was observed between kappa values for the two dichotomies (range = 0.16). The kappa values were not related to the experience of the endoscopist. Considerable variation in the agreement on diagnosis and grading of esophageal varices was found. These results must be taken into account in the assessment of trials of prophylaxis of first-time variceal bleeding.
Adult↗
Splanchnic and renal extraction of circulating type III procollagen aminoterminal propeptide in patients with normal liver function and in patients with alcoholic cirrhosis.
Splanchnic and renal extraction of circulating aminoterminal propeptide of type III procollagen and related antigens were studied in 12 patients with normal liver function and in 19 patients with alcoholic cirrhosis during catheterization. Type III procollagen peptide in serum was measured in two assays: the Type III Procollagen Peptide Radioimmunoassay Kit, a new assay that selectively determines the intact propeptide (and larger type III propeptide-holding antigens) and the Type III procollagen Fab assay that measures both the intact propeptide and the smaller fragments that quantitatively dominate in serum. A significant decrease in the concentration of the intact propeptide between the artery and the hepatic vein was found in the group with normal liver function (p less than 0.01) and in patients with cirrhosis (p less than 0.01). In patients with cirrhosis, however, the splanchnic extraction ratio of the intact propeptide (median = 0.04, range = -0.03 to 0.16) was significantly lower than in patients with normal liver function (median = 0.17, range = 0.05 to 0.36, p less than 0.01). The concentration of the intact propeptide in the hepatic vein was positively correlated to hepatic pressure (n = 18, r = 0.51, p less than 0.05) and inversely correlated to indocyanine green clearance (n = 15, r = -0.61, p less than 0.05). No splanchnic extraction could be demonstrated in the Type III propeptide Fab assay. A significant renal extraction was found in the Fab assay, but not in Type III Procollagen Peptide Radioimmunoassay Kit.(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗
Splanchnic removal of human alpha-atrial natriuretic peptide in humans: enhancement after food intake.
In order to assess the effect of food ingestion on splanchnic disposal of human alpha-atrial natriuretic peptide (ANF), hepatic-intestinal removal of ANF was determined before and after a test meal. Hepatic venous and arterial plasma samples were obtained from six subjects, most of whom had only disorders of minor degree. Hepatic blood flow (HBF) increased significantly after meal ingestion (1.10 +/- 0.17 [SEM] to 1.51 +/- 0.26 L/min, P less than .01). Baseline arterial ANF (10.9 +/- 3.1 pmol/L) did not change significantly. In contrast, hepatic venous ANF increased after meal intake (5.7 +/- 2.0 to 8.4 +/- 1.9 pmol/L, P less than .05), and accordingly the splanchnic fractional extraction decreased (0.53 +/- 0.09 to 0.35 +/- 0.08), although this was not statistically significant. Splanchnic clearance of ANF increased from 347 +/- 90 mL/min to a maximal value of 615 +/- 158 mL/min (P less than .05). Splanchnic removal of ANF was 3.0 +/- 0.5 pmol/min before and increased to a maximum value (7.1 +/- 2.2 pmol/min, P less than .05) 35 minutes after ingestion of the meal. Our results showed enhanced splanchnic removal of ANF after food intake. This is due to increased hepatic-intestinal clearance of the peptide consequent on increased splanchnic blood flow, rather than altered fractional extraction of ANF.
Aged↗
Effect of oral propranolol on circulating catecholamines in cirrhosis: relationship to severity of liver disease and splanchnic haemodynamics.
Patients with cirrhosis, especially those with decompensated disease have enhanced sympathetic nervous activity. We have investigated the effect of a single oral dose of 80 mg propranolol on circulating catecholamines and related the effect to splanchnic and systemic haemodynamics in 22 patients with cirrhosis. Plasma noradrenaline (NA) was significantly above normal average (NA: 0.52 vs. 0.23 ng/ml, p less than 0.01) and increased with the severity of the liver disease (p less than 0.01). NA was negatively correlated with liver function as estimated by ICG clearance (r = -0.74, p less than 0.01). Azygos blood flow was increased (0.75 l/min) and positively related to plasma NA (r = 0.57, p = 0.05, n = 12). After propranolol intake, plasma NA increased from 0.52 to 0.59 ng/ml (p less than 0.01). This response was found in all Child-Turcotte classes (A: 0.37 to 0.43; B: 0.49 to 0.56; C: 0.78 to 0.88 ng/ml), and in patients with as well as without ascites. Plasma adrenaline increased in the same way (p less than 0.01). Hepatic blood flow (from 1.10 to 0.93 l/min, p less than 0.01) and azygos blood flow (from 0.75 to 0.55 l/min, n = 9, p less than 0.05) decreased significantly after oral propranolol. A borderline significant correlation was observed between the decrease in azygos blood flow and the increase in NA (r = 0.64, p = 0.06). Our results suggest that besides a relationship to liver function and severity of disease, sympathetic nervous activity, as reflected by circulating NA, will further enhance during beta-adrenergic blockade, probably by a compensatory mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Duodenal ulcer healing on 2 g of sucralfate daily at bedtime compared to 1 g four times daily.
Seventy-seven patients with endoscopically verified duodenal ulcers were randomized to treatment with either 2 g sucralfate daily at bedtime or 1 g sucralfate q.d.s. in a controlled double-blind comparative study. After a 4-week treatment period, the healing rate was 68% for the former and 69% for the latter treatment.
Adult↗
Acyclovir in the prevention of duodenal ulcer recurrence.
This study tests the hypothesis that reactivation of a latent herpes simplex virus infection may be a cause of recurrent duodenal ulceration. Patients with recently healed duodenal ulcer were entered into a double blind, randomised study of maintenance treatment with the antiviral drug acyclovir (400 mg bid) versus placebo, to determine if suppression of herpes virus infection would influence the natural history of the ulcer disease. One hundred and fifteen patients entered the trial and 76 patients completed it according to the protocol. Endoscopy was performed when ulcer symptoms recurred and at the end of the 25 week trial period. In the acyclovir group the cumulated relapse rate was 63% compared with 56% in the placebo group (NS). This result suggests that reactivation of herpes simplex virus is not a cause of recurrent duodenal ulcer.
Acyclovir↗
Plasma volume changes during hypoglycaemia: the effect of arterial blood sampling.
To investigate whether previously reported changes in venous blood volume and composition induced by acute hypoglycaemia in humans are representative for the entire body we measured erythrocyte 51Cr content, haematocrit, plasma volume, intravascular albumin content and transcapillary escape rate of albumin in arterial and venous blood in seven healthy subjects before and during insulin-induced hypoglycaemia. In both vascular sites blood 51Cr content and the haematocrit increased, plasma volume and intravascular albumin content decreased and the transcapillary escape rate of albumin increased during hypoglycaemia. The magnitude of the changes in arterial and venous blood were not significantly different. These results indicate that the above changes in blood volume and composition are whole-body phenomena: furthermore, the major part of the changes are likely to occur in tissues other than upper extremity muscles.
Adult↗