Stefan Fuglsang

Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease

Background and aims: Cardiac dysfunction may be present in patients with cirrhosis. This study was undertaken to relate plasma concentrations of cardiac peptides reflecting early ventricular dysfunction (pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP)) to markers of severity of liver disease, cardiac dysfunction, and hyperdynamic circulation in patients with cirrhosis. Patients and methods: Circulating levels of proBNP and BNP were determined in 51 cirrhotic patients during a haemodynamic investigation. Results: Plasma proBNP and BNP were significantly increased in cirrhotic patients (19 and 12 pmol/l, respectively) compared with age matched controls (14 and 6 pmol/l; p<0.02) and healthy subjects (<15 and <5.3 pmol/l; p<0.002). Circulating proBNP and BNP were closely correlated (r = 0.89, p<0.001), and the concentration ratio proBNP/BNP was similar to that of control subjects (1.8 v 2.3; NS). Circulating proBNP and BNP were related to severity of liver disease (Child score, serum albumin, coagulation factors 2, 7, and 10, and hepatic venous pressure gradient) and to markers of cardiac dysfunction (QT interval, heart rate, plasma volume) but not to indicators of the hyperdynamic circulation. Moreover, in multiple regression analysis, proBNP and BNP were also related to arterial carbon dioxide and oxygen tensions. The rate of hepatic disposal of proBNP and BNP was not significantly different in cirrhotic patients and controls. Conclusion: Elevated circulating levels of proBNP and BNP in patients with cirrhosis most likely reflects increased cardiac ventricular generation of these peptides and thus indicates the presence of cardiac dysfunction, rather than being caused by the hyperdynamic circulatory changes found in these patients.

Dyssynchronous electrical and mechanical systole in patients with cirrhosis

BACKGROUND/AIMS Previous investigations have shown a prolonged QT interval in some patients with cirrhosis. The aim of this study was to investigate the relation between electrical and mechanical systole in patients with different degrees of severity of cirrhosis. METHODS Forty-eight patients with cirrhosis and portal hypertension, studied during a haemodynamic investigation, were compared to 17 controls. RESULTS A prolonged QTc (above 0.440 s(1/2)) was found in 37% of the cirrhotic patients vs. 5.9% in the controls (P=0.03), and there was a correlation to liver dysfunction (P<0.02). A direct relation between QT and time of mechanical systole (tS) was observed in controls (r=0.58, P<0.01), and cirrhotic patients (r=0.44, P<0.002). In patients with a prolonged QTc interval, the difference between electrical and mechanical systole time was substantially longer than in patients with a normal QTc interval (0.078 vs. 0.031 s, P<0.005). The QT values were related to markers of hyperdynamic circulation (r=-0.48 to 0.56, P<0.05-0.001). CONCLUSIONS; Prolonged repolarization, as evidenced by prolonged QTc, is related to both impaired liver function and systemic circulatory dysfunction. In addition these patients have alterations in the cardiac excitation-contraction relation with compromised association between electrical and mechanical function.

A randomized, placebo-controlled, crossover, double-blind trial of the NK1 receptor antagonist aprepitant on gastrointestinal motor function in healthy humans.

Background  Little is known about the role of tachykinins on human gastrointestinal motility and no data exist on the possible effect of an NK1 receptor antagonist.

Q‐T interval (QTC) in patients with cirrhosis: relation to vasoactive peptides and heart rate

Objective. Prolonged Q‐T interval (QT) has been reported in patients with cirrhosis who also exhibit profound abnormalities in vasoactive peptides and often present with elevated heart rate (HR). The aim of this study was to relate QT to the circulating level of endothelins (ET‐1 and ET‐3) and calcitonin gene‐related peptide (CGRP) in patients with cirrhosis. In addition, we studied problems with HR correction of QT. Material and methods. Forty‐eight patients with cirrhosis and portal hypertension were studied during a haemodynamic investigation. Circulating levels of ETs and CGRP were determined by radioimmunoassays. Correction of QT for HR above 60 beats per min was performed using the methods described by Bazett (QTC) and Fridericia (QTF). Results. Prolonged QTC (above 440 ms), found in 56 % of the patients, was related to the presence of significant portal hypertension and liver dysfunction (p<0.05 to 0.001), but not to elevated ET‐1, ET‐3 or CGRP. When corrected according to Bazett, QTC showed no significant relation to differences in HR between patients (r = 0.07, ns). QTF showed some undercorrection of HR (r = −0.36; p<0.02). During HR variation in the individual patient, QTC revealed a small but significant overcorrection (2.6 ms per heartbeat per min; p<0.001). This value was significantly (p<0.02) smaller with QTF (1.2 ms per heartbeat per min). Conclusions. The prolonged QTC in cirrhosis is related to liver dysfunction and the presence of portal hypertension, but not to the elevated powerful vasoconstrictor (ET‐1) or vasodilator (CGRP, ET‐3) peptides. The problems with correction of the QT for elevated HR in cirrhosis are complex, and the lowest HR should be applied for determination of the QT.

The influence of sacral nerve stimulation on gastrointestinal motor function in patients with fecal incontinence

Background  Sacral nerve stimulation (SNS) is a well‐established treatment for fecal incontinence of various etiologies. However, the mechanism of action remains unclear. The aim of the present study was to determine whether SNS affects gastric emptying, small intestinal transit or colonic transit times.

A kinetic compartment model for evaluating salivary gland scintigraphies.

The semi‐quantitative analysis of salivary gland scintigraphy with 99mTc‐pertechnetate has been used to evaluate salivary gland function. However, no objective parameters distinguishing abnormal from normal functions have been established thus far. We propose using a simple kinetic model applied to the four major salivary glands. This kinetic model is based on a two‐compartment model and the assumption of first‐order kinetics to characterize normal salivary gland function and other selected parameters to evaluate the normal function of salivary glands.

Arterial pressure profile in patients with cirrhosis: Fourier analysis of arterial pulse in relation to pressure level, stroke volume, and severity of disease: On the reduction of afterload in the hyperdynamic syndrome

Abstract Objective. Patients with cirrhosis have cardiovascular dysfunction and altered mechanical properties of large and small arteries. This study was undertaken in order to analyze the arterial pressure curve in relation to mean arterial pressure level, stroke volume, and severity of liver disease. Materials and methods. Forty-one patients with cirrhosis (Child–Turcotte classes A/B/C = 13/15/13) were studied during a hemodynamic investigation of portal hypertension. Fifteen patients without liver disease served as controls. We applied fast Fourier analysis to quantify the pressure components of the arterial curve, the harmonic Fourier coefficients (HFC). Results. Mean arterial pressure was significantly reduced (91 vs. 98 mmHg, p < 0.001) and stroke volume was significantly increased (94 vs. 78 ml, p < 0.001) in patients with cirrhosis versus controls. The HFC were significantly lower in patients with cirrhosis than in controls (–15 to –24%, p < 0.002), except for the fourth HFC, which was significantly increased (+28%, p < 0.02). In contrast to controls, which showed a highly significant effect of the level of arterial pressure on their HFC (p < 0.001), patients with cirrhosis did not show pressure or stroke volume dependence on their HFC, indicating an overall compliant and slow reflective arterial vascular bed. The initial rise in pulse pressure (dP/dt) was inversely related to the Child–Turcotte score (p < 0.05), and the HFC were borderline significantly related to this score (p = 0.07). Conclusions. The arterial pulsation in cirrhosis is qualitatively changed with reduced pulse reflections, which may protect against manifest cardiac failure in patients with advanced cirrhosis.

Fourier analysis of arterial pulse in patients with advanced cirrhosis indicates reduced wave reflections that may protect against manifest cardiac dysfunction

Several recent articles in Gut have dealt with different aspects of the systemic circulation in liver disease.1–4 Patients with advanced cirrhosis have cardiovascular dysfunction and altered mechanics of large and small arteries.5 ,6 The configuration of the arterial pressure curve from these patients may disclose a flatter profile with fewer peaks.7 However, systematic investigations have not been performed. We applied the fast Fourier analysis to quantify the components of the arterial pressure curve …

Gamma camera imaging for studying intestinal absorption and whole-body distribution of selenomethionine

Se metabolism in humans is not well characterised. Currently, the estimates of Se absorption, whole-body retention and excretion are being obtained from balance and tracer studies. In the present study, we used gamma camera imaging to evaluate the whole-body retention and distribution of radiolabelled selenomethionine (SeMet), the predominant form of Se present in foods. A total of eight healthy young men participated in the study. After consumption of a meal containing 4 MBq [⁷⁵Se]L-SeMet ([⁷⁵Se]SeMet), whole-body gamma camera scanning was performed for 45 min every hour over a 6 h period, every second hour for the next 18 h and once on each of the subsequent 6 d. Blood, urine and faecal samples were collected to determine the plasma content of [⁷⁵Se]SeMet as well as its excretion in urine and faeces. Imaging showed that 87·9 (sd 3·3)% of the administered activity of [⁷⁵Se]SeMet was retained within the body after 7 d. In contrast, the measured excretion in urine and faeces for the 7 d period was 8·2 (sd 1·1)% of the activity. Time-activity curves were generated for the whole body, stomach, liver, abdomen (other than the stomach and the liver), brain and femoral muscles. Gamma camera imaging allows for the assessment of the postprandial absorption of SeMet. This technique may also permit concurrent studies of organ turnover of SeMet.

Gamma-variate plasma clearance versus urinary plasma clearance of (51) Cr-EDTA in patients with cirrhosis with and without fluid retention.

In patients with fluid retention, the plasma clearance of 51Cr‐EDTA (Clexp obtained by multiexponential fit) may overestimate the glomerular filtration rate (GFR). The present study was undertaken to compare a gamma‐variate plasma clearance (Clgv) with the urinary plasma clearance of 51Cr‐EDTA (Clu) in patients with cirrhosis with and without fluid retention. A total of 81 patients with cirrhosis (22 without fluid retention, 59 with ascites) received a quantitative intravenous injection of 51Cr‐EDTA followed by plasma and quantitative urinary samples for 5 h. Clgv was determined from the injected dose relative to the plasma concentration‐time area, obtained by a gamma‐variate iterative fit. Clexp and Clu were determined by standard technique. In patients without fluid retention, Clgv, Clexp and Clu were closely similar. The difference between Clgv and Clu (Clgv – Clu = ΔCl) was mean −0·6 ml min−1 1·73 m−2. In patients with ascites, ΔCl was significantly higher (11·8 ml min−1 1·73 m−2, P<0·0001), but this value was lower than Clexp – Clu (17·5 mL min−1 1·73 m−2, P<0·01). ΔCl increased with lower values of GFR (P<0·001). In conclusion, in patients with fluid retention and ascites Clgv and Clexp overestimates GFR substantially, but the overestimation is smaller with Clgv. Although Clu may underestimate GFR slightly, patients with ascites should collect urine quantitatively to obtain a reliable measurement of GFR.