Relationship of systemic and intrarenal hemodynamics in cirrhosis

The relationship between systemic and renal hemodynamics was studied in 20 patients with advanced cirrhosis of the liver. Cardiac output was assessed by an indicator dilution technique, and both mean renal blood flow and intrarenal blood flow distribution were determined by the 133Xe washout method. Ten patients had elevated cardiac outputs (7.14 to 13.58 L/min; HCO group), seven patients had normal cardiac ouptputs (5.16 to 6.78; NCO group), and three had low cardiac outputs (3.65 to 4.1; LCO group). Renal hemodynamics did not correlate with cardiac output (r = 0.051; N.S.), since comparable reductions in mean renal blood flow occurred in both the LCO and HCO patients. Similarly, the degree of cortical ischemia, as assessed by percentage flow to the rapid flow component (C1%), did not correlate with cardiac output (r = 0.007; N.S.). Vasomotor instability as assessed by intrapatient variability of sequential xenon washout studies occurred frequently, and its magnitude did not correlate with cardiac output (r = -0.069; N.S.). These studies demonstrate that the abnormalities of intrarenal blood flow in cirrhosis are independent of alterations in cardiac output. Furthermore, the finding of marked intrarenal hemodynamic instability in the majority of patients with cirrhosis suggests that caution should be exercised in interpreting studies assessing the efficacy of vasoactive agents on renal hemodynamics in this disease, since the changes attributed to treatment may merely reflect spontaneous change.     

Exocrine pancreatic function in hepatic cirrhosis

Exocrine pancreatic function was assessed by the standard test meal method of Lundh in a control group, and 13 patients with nonalcoholic, postnecrotic cirrhosis of the liver. In six of these patients, splenorenal shunts were performed and exocrine pancreatic function was assessed before and three months after operation. In three of the six, the secretin-pancreozymin stimulation test was also performed. An increased volume but normal trypsin output was observed in the unoperated cirrhotic patients. An increase both in volume and in trypsin was found in the cirrhotic patients after shunting using the test meal stimulation. There was no appreciable difference, however, when tested with secretin and pancreozymin. Hypersecretion in cirrhotics, with or without shunts, is probably due to a by-pass of the hepatic degradation of normal pancreatic secretogogues produced by the intestine.     

Enhanced lipid peroxidation in hepatic cirrhosis

> Objective: This paper describes the deliberations of an interdisciplinary group of clinical and basic scientists who met at the National Institute of Child Health and Human Development to discuss the potential role of fetal behavior in assessing fetal well being and predicting neonatal outcome. The conference focused on three aspects of fetal behavior: 1) habituation; 2) state transitions; and 3) movement. Methods: The participants consisted of 25 leaders in the fields of obstetrics, perinatal medicine, neonatology, developmental psychobiology, developmental neuroscience, developmental psychology, ethology, and mathematics. The meeting was divided into three parts. In each of these a plenary speaker (a recognized expert in his field) began the session with an overview of the scientific theme. Two respondents, with research expertise in fetal research (animal models or human fetuses) followed with remarks on the plenary talk and comments based on their own studies. At the conclusion of these comments, the participants met in small groups to discuss the plenary proceedings and their implications for assessing human fetal well being and predicting outcome. At the conclusion of the small group deliberations all of the participants reconvened in a plenary session. During this part of the meeting a rapporteur from each small group summarized their discussions. Results and Conclusions: 1) Fetal habituation: there was a general consensus that research on this aspect of fetal behavior may have a high payoff for assessing human fetal well being and predicting neonatal outcome. 2) Behavioral state transitions: participants agreed that transitions afford investigators with an indication of when (timing) and how (models) behavior changes within and between developmental periods. Knowledge of transitions during development allows for tracking of behaviors that may be necessary for the fetus to adapt to its in utero environment or prepare for its postnatal life. 3) Chaos theory and fetal movement: participants concluded that non-linear dynamics systems analysis models could be useful to analyze "noise" within a measurement system; better define time scales; and increase resolution and thereby better identify "signals."     

Influence of nitroglycerin on portal pressure and gastric mucosal hemodynamics in patients with cirrhosis

We studied 30 patients with cirrhosis to determine the effect of nitroglycerin on portal and gastric mucosal hemodynamics. Systemic hemodynamics, portal venous pressure (PVP), the hemoglobin index (IHB), and the oxygen saturation index (ISO2) of the gastric mucosa were measured before and after a continuous infusion of nitroglycerin. The patients were divided into two groups according to the presence or absence of major portal-systemic collateral routes on portograms. Nitroglycerin caused a reduction in PVP in all patients. Although there was no significant difference in systemic hemodynamic changes between the two groups, the reduction in PVP in patients with major portal-systemic collaterals was significantly higher than in those without major collaterals. A nitroglycerin infusion, at a dose of 1.0 micrograms/kg per min for 10 min, produced a reduction in both IHB (-16%, P < 0.001) and ISO2 (-13%, P < 0.001) in the gastric mucosa, indicating gastric mucosal ischemia secondary to splanchnic vasoconstriction. These findings suggest that the continuous infusion of nitroglycerin reduces PVP in cirrhotic patients, particularly in those with major portal-systemic collaterals, and reduces the congestion of the gastric mucosa in patients with portal hypertension.     

Pulmonary hypertension: a rare complication of hepatic cirrhosis

Pulmonary hypertension is a rare pulmonary complication of chronic hepatic diseases. Anatomopathologic and clinic data are very similar to primary pulmonary hypertension. Although the lesions of arteriopathy are more related to portal hypertension than to hepatic lesions, the physiopathology of this morbid association is unknown.     

The abnormal hepatic scan of chronic liver disease: its relationship to hepatic hemodynamics and colloid extraction

To help explain the characteristic hepatic scan pattern of chronic liver disease, the degree of scan abnormality (scan score, SS) after administration of technetium-99m sulfur colloid (Tc) was compared with data obtained at hepatic vein catheterization in 28 patients. Although SS showed a correlation with wedged hepatic vein pressure (r = +0.491), the scan abnormality was not directly due to portal hypertension because it remained unchanged when the latter was relieved by portacaval shunt. Also, the scan abnormality was found to be unrelated to a low hepatic blood flow. Scan abnormality was not attributable primarily to hyperactivity of the reticuloendothelial (RE) cells of the spleen and bone marrow since fractional clearance (K) of Tc from the blood was decreased rather than increased in patients with abnormal scans. SS was inversely correlated with K or Tc (r = -0.575) and with hepatic extraction efficiency for Tc (r = -0.673), showing that the basic abnormality was poor extraction of the colloid by the RE cells of the liver with a resultant increase in the amount available for extrahepatic localization. Indirect evidence suggests that this poor extraction of colloid is due to intrahepatic shunts bypassing hepatic RE cells.     

Tamoxifen in liver disease: potential exacerbation of hepatic dysfunction

Tamoxifen, a non-steroidal anti-estrogen, has been used successfully for a decade as post-operative adjuvant therapy for breast cancer. Tamoxifen is generally well tolerated with few side effects, especially at the typical dose of 10 mg twice daily. However, hepatic effects have been reported after tamoxifen administration and are usually found to be cholestatic in nature. Although previous reports concentrate on tamoxifen as a probable cause of drug-induced hepatotoxicity, very little attention has been focused on the use of tamoxifen in patients with pre-existing liver dysfunction and the possible need for dose adjustment. We present the case of a 48-year-old woman with an acute exacerbation of her pre-existing liver dysfunction and subsequent elevations of tamoxifen blood levels after approximately one year of tamoxifen therapy for adjuvant treatment of breast cancer. Tamoxifen dosing was adjusted based on serum levels.     

Portal hemodynamics after large-volume paracentesis in patients with liver cirrhosis and tense ascites

Large-volume paracentesis with a plasma expander has been extensively evaluated and shown to be an effective and safe therapy. While hepatic and systemic hemodynamics have been studied extensively, there is little information on portal hemodynamics by duplex Doppler. Portal vein diameter, portal flow velocity, and portal blood flow were measured with duplex Doppler in 11 cirrhotic patients before and 24 hr after large volume paracentesis. There were no significant changes in the portal vein diameter (9.88+/-2.62 mm vs 10.09+/-2.73 mm), portal flow velocity (10.65+/-2.60 vs 10.01+/-2.58 cm/sec), and portal blood flow (488+/-288.9 vs 502+/-73.38 ml/min), before and 24 hr after large-volume paracentesis. Thus, significant changes in portal hemodynamics do not occur after large-volume paracentesis.     

GH secretion after L-dopa administration in hepatic cirrhosis

A 500 mg L-Dopa administration in normal and cirrhotic subjects does not determinate a significant varation of plasma glucose and insulin level, while a peak plasma GH level in both cirrhotic and normal subjects occurred at 90' with a significantly greates values in cirrhotics. It is doubtful to affirm that a high plasma GH level is the only one factor which responsable of glucose intolerance in cirrhotic subjects, when there are many others factors contribute to it in synergic way. In order to elucidate the hypothesis on possible pathogenetic mechanism it is discussed some of our own experience and observations.     

Vagal dysfunction and impaired urinary sodium and water excretion in cirrhosis

OBJECTIVE: To evaluate the possible role of vagal impairment in the disturbances of urinary sodium and water excretion observed in cirrhosis. METHODS: Standard cardiovascular reflex tests were used to assess Autonomic function in 11 cirrhotic patients, and the response to an acute intravenous water load was determined. Changes in plasma noradrenaline, antidiuretic hormone, renin, and atrial natriuretic peptide also were evaluated. RESULTS: Patients with vagal dysfunction were shown to have significantly impaired urinary sodium and water excretion, compared with those whose cardiovascular tests were normal (5-h urinary sodium excretion, 32.3 +/- 9.0 vs. 69.4 +/- 12.7 mmol, p < 0.05; % water load excreted at 5 h, 67.8 +/- 10.5 vs. 109.2 +/- 3.67%, p < 0.008). This was associated with higher circulating noradrenaline, renin, and antidiuretic hormone levels after the water load in the vagal dysfunction group. Urinary sodium excretion correlated with the heart rate variation on deep breathing (r = 0.74, p < 0.013) and the heart rate response to atropine (r = 0.75, p < 0.020); the % water load excreted correlated with the number of abnormal cardiovascular tests in each patient (rS = 0.67, p < 0.02). Although patients with vagal abnormalities had worse liver function, urinary sodium and water excretion correlated better with parasympathetic tests than with standard parameters of hepatic function. CONCLUSIONS: The presence of vagal impairment in cirrhosis appears to be associated with impaired urinary sodium and water excretion, as well as disturbances in circulating vasoactive hormones. These findings could be due to an afferent defect resulting in diminished inhibitory input from intrathoracic volume and arterial baroreceptors, although a confounding effect of worse hepatic function in patients with vagal impairment cannot be excluded.     

Postoperative hepatic dysfunction in perspective. 1970

We measured the autoantibodies to GM1, central myelin proteins, and cardiolipin in 30 GBS patients using sensitive ELISA and Western blot techniques. The sequential modifications of titers during plasma-exchange (PE) and at follow-up were investigated in 15 patients. In pretreatment sera, we found significantly increased antibody titers to GM1 (37% of the patients), central myelin proteins (28%), and cardiolipin (21%). Seventeen patients out of 29 (58%) presented increased IgG or IgM antibody to at least one of the antigens considered as compared to 10 out of 70 controls (14%, P = 0.00001). By Western blot, IgG or IgM antibodies reactive with the triton insoluble fraction of central myelin were observed in 19 out of 28 GBS patients (67%). The follow-up measurements during and after PE showed a declining autoantibody titer in 10 out of 15 patients. However, in the remaining 5 GBS patients, we observed a persistently elevated titer or an increase from baseline values occurring during or after PE and reaching a peak. In 2 of the 5 patients, the titer peak preceded a clinical re-exacerbation. The presence of a persistently elevated or an increasing autoantibody titer during treatment with PE merits further investigation and may help to clarify the pathogenesis of GBS and improve its treatment.     

Role of the hepatic xanthine oxidase in thyroid dysfunction: effect of thyroid hormones in oxidative stress in rat liver

Temporary vocal fold immobility resolving in 4 weeks or less is considered a transient immobility. Many different disorders may lead to this type of laryngeal motion impairment. It is important for otolaryngologists to be familiar with the differential diagnosis for transient vocal fold immobility in order to optimize the management of these unusual cases.     

Mitochondrial respiratory chain succinate-cytochrome-c oxidoreductase deficiency and hepatic cirrhosis

OBJECTIVES: The current need to evaluate necessity and cost of diagnostic and therapeutic procedures extends to transplant services. We reviewed our experience over the past 3 years as we have moved away from routine post-transplant nuclear medicine scans, ultrasounds, and cystograms. METHODS: From January 1, 1992 to December 31, 1994, 252 kidney transplants were performed at Virginia Mason Medical Center. There were 74 live donor and 178 cadaver donor kidneys transplanted. The records of these patients were reviewed for the type and number of post-transplant imaging done during their initial hospitalization. RESULTS: During the study period, the number of post-transplant imaging studies per patient decreased from 2.7 to 1.4 (P = 0.000), the percentage of patients discharged without any studies rose from 2.8% to 24.4% (P = 0.001), and the trend in 1-year actual graft survival increased from 84.7% to 93.0% (P = 0.187). CONCLUSIONS: Post-transplant imaging studies can be safely reduced. Many patients with good initial graft function can avoid having any studies.     

Characteristics of the effect of nitroglycerin on hemodynamics

An examination was conducted of 45 healthy individuals 23 to 28 years of age who received nitroglycerine sublingually in a dose of 0.5 mg (15 persons) and by intravenous drip for one hour in doses of 3, 10, and 20 mg (groups of ten persons). It was shown that the drug had no essential effect on the rate of cardiac contractions and the diastolic arterial pressure. The systolic arterial pressure decreased with the increase of the nitroglycerine dose. The trend and the severity of changes in central hemodynamics were, in most cases, inversely dependent on the volume of cardiac ejection and did not depend on the dose and route of administration of the drug. With a cardiac index of 3 to 5.5 1/min/m2, this index in 71% of individuals reduced by 26% on the average. With an initial cardiac index of 2 to 2.9 1/min/m2, in 63% of individuals this index increased by 27% on the average. The authors distinguish three types of the reaction of hemodynamics to the administration of nitroglycerine: hypo-, hyper-, and eucardiac.