Hepatic involvement in hereditary hemorrhagic telangiectasia: CT findings.

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal-dominant vascular disease characterized by mucocutaneous or visceral angiodysplastic lesions (telangiectases and arteriovenous malformations) that may be widely distributed throughout the cardiovascular system. The recognition of mucocutaneous telangiectases, the occurrence of spontaneous and recurrent episodes of epistaxis, the presence of visceral involvement, and a family history of this disease are the clinical criteria that allow diagnosis. In comparison with skin, lungs, gastrointestinal tract, and brain involvement, hepatic involvement defined by clinical criteria alone has long been considered uncommon. Our experience with a large group of HHT patients, even those asymptomatic for liver involvement, demonstrates that it is more frequent than reported and is characterized by the presence of intrahepatic shunts, disseminated intraparenchymal telangiectases, and other vascular lesions. Congestive cardiac failure, portal hypertension, portosystemic encephalopathy, cholangitis, and atypical cirrhosis have been reported as possible serious complications related to this condition. Thus, a correct diagnosis is important, and diagnostic imaging has a fundamental role in detecting alterations involving the liver. The possibilities to perform a multiphasic study and to provide high-quality multiplanar and angiographic reconstructions, gives multidetector row helical computed tomography the ability to detect and characterize the complex anatomopathologic alterations typical of this disease.

Haemodynamic effects of propranolol, octreotide and their combination during fasting and post-prandial splanchnic hyperaemia in patients with cirrhosis.

BACKGROUND/AIMS: This double-blind study was designed to evaluate the haemodynamic effect of two drugs, propranolol and octreotide, and their combination in patients with cirrhosis. METHODS: Fifteen patients with cirrhosis were randomly assigned to two groups receiving either octreotide subcutaneously at 100 microg ('octreotide' group, n = 9) or propranolol orally at 40 mg followed by a subcutaneous dose of octreotide (100 microg) after 1 h ('propranolol + octreotide' group, n = 6); then, after 30 min, a standard meal was administered to both groups. The hepatic vein pressure gradient by hepatic vein catheterization, portal and superior mesenteric artery blood flow velocity, superior mesenteric artery pulsatility index by the echo-Doppler duplex system were recorded at baseline, 1 h after propranolol in the 'propranolol + octreotide' group, and in both groups 30 min after octreotide and 30 min after meal. RESULTS: At fast, propranolol was more active in decreasing portal pressure (from 16 +/- 2.2 to 12.7 +/- 3.8 mmHg, -20%, P < 0.05) as compared to octreotide (from 18.6 +/- 4.8 to 16.6 +/- 4.3 mmHg, -11%, P < 0.05). Conversely, octreotide was more active on the mean blood flow velocity of superior mesenteric artery (from 22.8 +/- 5 to 19 +/- 4.5 cm/ s, -17%; P< 0.05). Octreotide administration in patients receiving beta-blockers showed, also, a trend to increase the mesenteric vascular resistances (pulsatility index from 3.14 +/- 0.69 to 3.68 +/- 1.29, +17%, not significant (NS)) which had not been affected by previous treatment with propranolol. After the meal, a reduction of the expected hyperaemic response occurred in both groups. CONCLUSIONS: The combined acute haemodynamic effect of this association suggests the possible combination of these two drugs in critical situations, such as variceal bleeding in patients receiving beta-blockers. The simultaneous use of echo-Doppler and hepatic vein catheterization permitted us a more complete analysis of the acute haemodynamic events.

Effect of chronic treatment with nadolol plus isosorbide mononitrate on liver blood flow and liver metabolic activity in cirrhosis.

OBJECTIVE: To assess the long-term effect of the addition of long-acting nitrates to beta-blockers on liver blood flow and liver metabolic activity in patients with cirrhosis and portal hypertension. METHODS: Eleven patients with cirrhosis and portal hypertension were investigated by using hepatic vein catheterization and indocyanine green (ICG) constant infusion on baseline conditions, after 1 month of treatment with nadolol, after 3 months of treatment with nadolol plus isosorbide mononitrate, and (in seven cases) after 1 year of combined treatment. RESULTS: The hepatic venous pressure gradient decreased significantly after nadolol, and more so after addition of isosorbide mononitrate. Hepatic blood flow, and ICG intrinsic hepatic clearance did not change significantly, although few cases showed an increase or decrease in either parameter. A significant correlation was found between changes in ICG intrinsic hepatic clearance and in hepatic venous pressure gradient (r = 0.62, P = 0.04). CONCLUSIONS: Liver blood flow and liver metabolic activity are not consistently affected by addition of isosorbide mononitrate to nadolol. Substantial decreases in portal pressure may be associated with a decrease in ICG intrinsic hepatic clearance.

Interobserver and interequipment variability of hepatic, splenic, and renal arterial Doppler resistance indices in normal subjects and patients with cirrhosis.

BACKGROUND/AIMS: Doppler arterial resistance indices are used to evaluate alterations in arterial hemodynamics in the liver, spleen, and kidney. The purpose of this study was to determine the interobserver and interequipment variability of hepatic, splenic, and renal arterial Doppler resistance indices, and the influence of a cooperative training program of the operators on the reproducibility of the results. METHODS: In the first part of the study, hepatic (PI-L, RI-L), splenic (PI-S, RI-S), and renal (PI-K, RI-K) pulsatility and resistive indices were measured by echo-color-Doppler in eight control subjects and ten patients with cirrhosis by three operators using three different machines. In the second part of the study, measurements were taken by the three operators in nine controls and nine patients with cirrhosis, after cooperative training, with a single machine. RESULTS: Significant interobserver variability was present for all parameters except RI-L. Significant interequipment variability was present for all parameters except PI-S and RI-S. Only 0-3% of variance was equipment- or operator-related, while 58-72% was patient-related. Hepatic and renal coefficients of variation were similar in patients with cirrhosis and controls, while splenic coefficients of variation were higher in patients with cirrhosis than in controls. After training, differences among operators disappeared for all variables except RI-K, and the operator-related component of variance nearly disappeared for all parameters. CONCLUSIONS: Hepatic, splenic, and renal arterial resistance indices show small but significant interobserver and interequipment variability. Interobserver variability can be decreased to non-significant levels by a common training program. Thus, these indices can be widely applied to the study of arterial circulation in these organs.

Oxidation of circulating proteins in alcoholics: role of acetaldehyde and xanthine oxidase.

BACKGROUND/AIMS: This study aimed to evaluate the protein and lipid redox status in plasma erythrocytes and erythrocyte ghosts of alcoholics and of patients with non-alcoholic liver disease; we also investigated the relation to glutathione levels and the role of acetaldehyde and xanthine oxidase activity in plasma. METHODS: Carbonyl and sulfhydryl proteins, glutathione and malondialdehyde levels and the activity of the circulating xanthine oxidase were determined in: active and abstinent alcoholics, patients with chronic viral hepatitis and healthy controls. RESULTS: Active alcoholics showed a decrease of sulfhydryl protein and glutathione concentrations in plasma, erythrocytes and ghosts compared to the other groups. Also, an increase of the carbonyl protein and malondialdehyde levels and of the activity of circulating xanthine oxidase (9.2 +/- 1.8 nmol.min.ml, p < 0.001) were observed. Significant correlations between carbonyl protein and malondialdehyde concentrations in plasma (r = 0.775, p < 0.001), as well as between daily alcohol intake and carbonyl protein content in plasma (r = 0.879, p < 0.001) and erythrocytes (r = 0.605, p < 0.01) were observed. However, carbonyl protein levels did not correlate with the degree of liver injury. Incubation of plasma with acetaldehyde, but not with ethanol, significantly increased the carbonyl protein formation. Administration of N-Ethylmaleimide, a thiol depletor, or glutathione significantly increased or delayed, respectively, the carbonyl protein formation. CONCLUSIONS: Proteins are oxidatively modified in plasma and erythrocytes of active alcoholics, whereas no such alterations are detectable in patients with non-alcoholic liver disease. Protein oxidation in alcoholics does not seem to result directly from ethanol; circulating xanthine oxidase, delivered from injured cells, may play a contributory role and glutathione appears to be directly involved in the protection of plasma proteins against acetaldehyde toxicity.

Octreotide blunts postprandial splanchnic hyperemia in cirrhotic patients: a double-blind randomized echo-Doppler study.

The effect of octreotide, a long-acting synthetic analog of somatostatin, on fasting and postprandial splanchnic hemodynamics was investigated in cirrhotic patients. Splanchnic hemodynamics were assessed using an echo-Doppler duplex system in a prospective, double-blind, placebo-controlled, crossover study performed on 2 separate days, 1 week apart, in 30 cirrhotic patients. Measurements of portal vein (PV) cross-sectional area (PV-A) and mean velocity (PV-V), and of superior mesenteric artery (SMA) mean velocity (SMA-V) and pulsatility index (SMA-PI) (an index of vascular resistance) were performed at baseline, 30 minutes after octreotide (200 micrograms subcutaneously) or placebo administration, and 30 and 60 minutes after the ingestion of a liquid meal. In the fasted state, octreotide induced a significant decrease in PV-V (-7%) and in SMA-V (-10%) and an increase in PI (+16%). On the day of placebo administration, meal ingestion induced a significant increase in PV-V (+21%) and in SMA-V (+43%) and a decrease in PI (-21%). In contrast, meal ingestion on octreotide day induced significantly smaller increases in PV-V (+10%) and in SMA-V (+18%) and a significantly smaller decrease in PI (-10%). Octreotide, although producing a mild reduction in PV-V and SMA-V in the fasted state, markedly blunts postprandial splanchnic hyperemia in cirrhotic patients.

Comparison between the effect of L-propionylcarnitine, L-acetylcarnitine and nitroglycerin in chronic peripheral arterial disease: a haemodynamic double blind echo-Doppler study.

The haemodynamic effects on the peripheral vascular bed of L-acetylcarnitine, L-propionylcarnitine, and nitroglycerin were tested by echo-Doppler in a double blind cross-over study. Eleven male patients suffering from peripheral arterial obliterative disease (PAOD) in the second stage of Fontaine's classification, and 11 matched control subjects were enrolled in the study. Each subject received one of three different treatments on each day of the study in a different order following a random assignment. The treatments were either 30 mg x kg of L-acetylcarnitine (LAC) or 30 mg x kg of L-propionylcarnitine (LPC) or nitroglycerin (NTG) 1.25 mg given as a single i.v. bolus injected over 3 min. Echo-Doppler measurements of blood flow velocity, and cross-sectional area of the femoral artery were performed at baseline and 10, 20, and 30 min after injection of the drugs. Pulsatility Index (an index derived from the blood flow velocity and related to vascular resistance: PI = Vmax - Vmin/Vmean) was also obtained each time. Results were analysed using a Student's t-test for paired data. L-acetylcarnitine and L-propionylcarnitine showed no haemodynamic effects in either group of subjects (controls and PAOD patients) whether blood flow or vascular resistance was considered. There were haemodynamic changes (a decrease in blood flow velocity and an increase in arterial systemic resistance) only after NTG administration. The changes were more evident in controls than in PAOD patients. Femoral artery cross-sectional area showed no statistically significant effect as regards treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Echo-color Doppler in the study of portal hypertension]. / Eco color-Doppler nello studio dell'ipertensione portale.

Color-Doppler US is currently an extremely valuable tool in the study of abdominal circulation, cirrhosis of liver and its complications, different kinds of portal hypertension, vascular/avascular liver malformations and, finally, in the evaluation of liver transplants. Moreover, its use in experimental studies has yielded good results. Even spontaneous porto-systemic shunts can be demonstrated in most cases (up to 88%). Color-Doppler allows partial obstructions to be demonstrated and permits qualitative and quantitative dynamic evaluations the presence/absence of flow, vascular masses--e.g., mean velocity measurement and blood flow assessment. The interobserver variability of the method was calculated with a double-blind study carried out by our laboratory team cooperating with a study group from the University of Yale, USA. The study evidenced how color-Doppler US cannot be used to follow the single patient unless the variations to measure are higher than variability itself. Color-Doppler limitations depend on the subjectivity of the results and on its difficult application to obese patients or to those with severe intestinal meteorism.

Echo-Doppler evaluation of acute flow changes in portal hypertensive patients: flow velocity as a reliable parameter.

In order to evaluate the behavior of the portal vein cross-sectional area during changes in portal flow, two groups of subjects were analyzed in two blinded cross-over studies using echo-Doppler flowmetry. The first group (I) consisted of 21 patients with cirrhosis and 16 controls. They received a standardized meal which is known to increase portal flow. The second group (II) consisted of 31 patients with cirrhosis who received a dose of propranolol which is known to decrease portal flow. In Group I, 30 min after the meal, the portal vein blood velocity increased by 35 +/- 6% (p less than 0.01) in cirrhotic patients and by 55 +/- 5% (p less than 0.01), in normal subjects. The portal vein cross-sectional area increased significantly in normal subjects (22 +/- 2%, p less than 0.01) but not in cirrhotic patients (4 +/- 2%, n.s.). In Group II, 2 h after propranolol, there was a significant decrease in portal blood velocity (-14 +/- 2%), whereas the portal vein cross-sectional area did not show any significant changes. These data demonstrate that, in portal hypersensitive patients, the portal area measured by echo-Doppler flowmetry can be assumed to be constant and hence its calculation to estimate changes in portal blood flow can be omitted. Therefore, the use of blood velocity alone is suggested to monitor acute changes in flow in portal hypertension using Doppler flowmetry. The elimination of the portal vein cross-sectional area measurement simplifies the quantitative calculation of portal hemodynamics and increases the reliability of the technique by avoiding a source of error.

A randomized study of propranolol on postprandial portal hyperemia in cirrhotic patients.

Propranolol, a nonselective beta-adrenergic blocker, has been shown to reduce portal pressure and the risk fo variceal bleeding. The portal pressure-reducing effect of propranolol is mediated by splanchnic arterial constriction, which decreases portal flow. A double-blind randomized control study (crossover on 2 consecutive days) was designed to compare the effects of propranolol vs. placebo on portal flow in cirrhotic patients during fasting and after a standardized meal. Portal flow was measured with an ATL Ultramark 8 echo-Doppler system (Advanced Technological Laboratories, Bothel, WA) in 23 cirrhotic patients. Fasting portal flow and heart rate were obtained at baseline and 2 hours after the administration of propranolol or placebo. A standard test meal was then given, and measurements were repeated 30 minutes later. Thirteen patients (group 1) received placebo on day 1 and propranolol on day 2, whereas 10 patients (group 2) received propranolol on day 1 and placebo on day 2. In group 1 patients, heart rate declined by 20% (P less than 0.0001) and portal flow decreased by 12% (P less than 0.05) after propranolol administration. Similar reductions were found in heart rate (-21%, P less than 0.0001) and portal flow (-17%, P less than 0.001) for group 2 patients. For all 23 patients, 2 hours after propranolol administration, heart rate declined by 21% (P less than 0.0001) and portal blood flow was reduced by 14% (P less than 0.0001). The 10 patients who received propranolol on day 1 (group 2) showed a carryover effect of propranolol on day 2. On day 2, baseline portal flow and heart rate values were significantly lower than baseline values on day 1. This long-lasting effect of a single dose of propranolol may be caused by the longer half-life of propranolol in cirrhotic patients. The postprandial portal blood flow percentage increase after the meal was similar for both placebo and propranolol. Propranolol did not blunt postprandial hyperemia. However, whereas the absolute value of blood flow after the meal increased significantly in comparison with baseline in placebo-treated patients (P less than 0.001), this did not occur with propranolol. Furthermore, in propranolol-treated patients the absolute value of blood flow after the meal was lower than in placebo-treated patients. This may constitute a protective effect of propranolol in portal hypertension.

Echo Doppler duplex scanner and color in the study of portal hypertension.

In the present state of the art, the Doppler duplex scanner provides much information about portal hypertension and its associated pathology, liver cirrhosis, hepatic malformations, vascular or avascular structures, hepatic transplants, and ascites. Its usefulness for experimental studies, providing new insight into the pathophysiology of this disease, has been proven. It is limited by the subjectivity of the conclusions, and by its poor feasibility in fat patients and those with excessive abdominal gas. However, the noninvasive nature of Doppler and its relative low cost make it a useful first step in the evaluation of portal hypertension.

Evaluation of postprandial hyperemia in superior mesenteric artery and portal vein in healthy and cirrhotic humans: an operator-blind echo-Doppler study.

In an operator-blind design, we used an echo-Doppler duplex system to examine superior mesenteric artery and portal vein hemodynamics on two consecutive mornings in 12 fasting cirrhotic patients and 12 matched controls, randomized to a standardized 355 kcal mixed-liquid meal vs. water. Cross-sectional area and mean velocity were recorded from the portal vein and superior mesenteric artery at 30 min intervals, from 0 min to 150 min after ingestion. Flows were calculated. Pulsatility index, an index related to vascular resistance, was obtained for the mesenteric artery. Baseline flows did not differ between cirrhotic patients and control patients, but pulsatility index was reduced in the cirrhotic subjects. Maximal postprandial hyperemia was attained at 30 min. Cirrhotic patients showed a blunted hyperemic response to food. In normal controls, portal vein area increased significantly after the meal from 30 min to 150 min, whereas in cirrhotic patients a significant difference occurred only at 30 min. Pulsatility index in both groups was significantly reduced after eating, and this reduction persisted up to 150 min. No changes after ingestion of water were observed. Echo-Doppler was very sensitive in detecting postprandial splanchnic hemodynamic changes and differences between cirrhotic patients and normal subjects. Mesenteric artery pulsatility index was more sensitive than flow in detecting baseline hemodynamic differences. In cirrhotic patients, portal postprandial hyperemia was mainly related to the increase in mean velocity.

13C-NMR measurements of muscle glycogen during low-intensity exercise.

Glycogen metabolism in exercising gastrocnemius muscles was examined by natural abundance 13C nuclear magnetic resonance (NMR) spectroscopy. Five-minute 13C-NMR measurement of muscle glycogen had a reproducibility of +/- 6.5% (+/- 4.8 mM). Experiments were performed on healthy fed male and female subjects. Two protocols were followed. 1) Subjects performed plantar flexion from rest at 15, 20, or 25% of maximum voluntary contraction for up to 9 h. 2) Subjects predepleted gastrocnemius glycogen with heavy exercise and then either performed low-intensity exercise as before or rested. Gastrocnemius glycogen was measured by NMR at rest and after each hour of exercise. In some sessions, both the exercised leg and the nonexercised leg were monitored with 13C-NMR. In protocol 1, blood velocity in the femoral artery was similarly assessed with ultrasonography. During low-intensity exercise from rest (protocol 1) muscle glycogen fell to a new steady-state value after several hours and then remained constant despite continued exercise. Mean blood velocity increased ninefold within 2 min of onset of exercise and remained constant thereafter. After predepletion (protocol 2), muscle glycogen was repleted both during low-intensity exercise and at rest. After 1 h the amount of glycogen repletion was greater when coupled with light exercise [48.5 +/- 2.8 mM after 1 h of exercise, 39.7 +/- 1.1 mM after 1 h of rest (P less than 0.05)]. During subsequent light exercise, glycogen reached a steady-state value similar to that obtained in protocol 1, while in resting, recovery glycogen levels continued to increase (+2.7 mM/h) over a 7-h period.(ABSTRACT TRUNCATED AT 250 WORDS)

[Strain-gauge plethysmographic measurement of the systemic bioavailability of oral nitroglycerin in liver cirrhosis]. / Misura mediante pletismografia strain-gauge della biodisponibilita' sistemica della trinitrina per os in corso di cirrosi epatica.

7 cirrhotic (M = 3, F = 4, mean age 55, range 35-74) and 7 healthy subjects (M = 6, F = 1, mean age 24, range 23-40) were studied. 2.5mg% nitroglycerin were administered per os. This drug is quite completely metabolized in its first pass through the liver (first pass effect). Peripheric vascular effect of nitroglycerin was evaluated by venous occlusion strain-gauge plethysmography, ECG-coupled (Rest Flow measurement RF, in ml/min/100 ml). No statistically significant differences were found between pre-drug RF in the two groups and between pre and post-drug measurements in healthy subjects. Post-drug RF decreased in cirrhotic subjects when compared either to pre-drug values or to post-drug values in normal subjects (statistically significant after the third minute, p ranging less than 0.05 and less than 0.001). The different peripheric vascular effect found in the two groups was considered as a consequence of the increased drug bioavailability in cirrhotics, caused by portosystemic shunts.