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Biomedical subjects

J H Henriksen

Publications and source records attributed to J H Henriksen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: a randomized, double-blind, controlled trial.

Octreotide seems to have a beneficial effect on variceal bleeding, and long-term administration for the prevention of rebleeding is currently being evaluated. Experimental studies have suggested a beneficial effect of chronic octreotide treatment on renal function, while clinical studies have shown variable effects. Twenty-five cirrhotic patients with portal hypertension were randomized in a double-blind design to placebo or a single subcutaneous dose of a long-acting formulation of octreotide (octreotide-LAR) (20 mg). Renal function tests were performed before dosing and repeated after 30 days. The patients were in sodium steady state at the time of study. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by a constant infusion clearance technique. Renal sodium handling was determined by lithium and sodium clearance measurements. Therapeutic serum levels of octreotide along with a reduction of insulin-like growth factor I (IGF-I) (P <.01) and an increase of IGF binding protein 1 (P <.05) were demonstrated. No effect of octreotide was observed on GFR, ERPF, or filtration fraction (GFR/ERPF). Changes in clearance and extraction fraction of sodium and lithium during octreotide treatment were not significantly different from those of placebo. In addition, no changes in free water clearance, urinary flow rate, or 24-hour Na excretion were demonstrated. A significant increase of mean arterial pressure (+5 mm Hg; P <.01) was observed after treatment with octreotide-LAR. It is concluded that in spite of increased arterial pressure, octreotide-LAR has no significant effect on renal hemodynamics and tubular function in clinically stable cirrhotic patients with portal hypertension.

Blood Pressure↗
PubMed2001

A comparison of circulating and regional growth hormone-binding protein in cirrhosis.

The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis is disturbed in cirrhosis, with elevated basal GH and low IGF-I levels relating to liver function and prognosis. In plasma, GH is bound to a high-affinity GH-binding protein (GHBP), which has been found to be slightly reduced in cirrhosis, but with huge variations. GHBP is identical to the extracellular part of the hepatic GH receptor, but other tissues may contribute to the circulating GHBP levels. The aim was therefore to measure circulating and regional concentrations of GHBP in relationship to hepatic function and body composition in patients with cirrhosis (n = 38) and controls with normal liver function (n = 29). Blood samples from the hepatic, renal, and femoral veins and the femoral artery were collected simultaneously during a hemodynamic investigation. Plasma GHBP was directly measured by a specific and sensitive fluoroimmunoassay. Circulating GHBP levels were identical in the patients and controls (mean +/- SD) 1.03 +/- 0.56 nmol/L and 1.02 +/- 0.55 nmol/L, respectively (not significant). We found no significant hepatic, renal, or peripheral arteriovenous extractions or generations of GHBP, and it did not significantly correlate to liver function. In the controls, GHBP correlated significantly with body mass index (BMI) (r =.60, P <.005), whereas this relationship was not found in the patients with cirrhosis. In conclusion, high-affinity GHBP appears to be normal in patients with cirrhosis, with no significant hepatic generation or renal extraction and no association with the severity of the liver disease. Thus, our study supports the hypothesis that tissues other than the liver, despite its abundant GH receptors, may contribute to the circulating GHBP.

Aged↗
PubMed2001

Vasoactive substances in the circulatory dysfunction of cirrhosis.

Patients with cirrhosis and portal hypertension exhibit characteristic haemodynamic changes with a hyperkinetic systemic circulation, abnormal distribution of the blood volume, and neurohumoral dysregulation. Moreover, the circulating levels of several vasoactive substances may be elevated. Splanchnic vasodilatation is of pathogenic significance for the low systemic vascular resistance and abnormal volume distribution, which are important elements in the development of the concomitant cardiac dysfunction, recently termed cirrhotic cardiomyopathy. The systolic and diastolic functions are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms seem to include a reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling, and conductance abnormalities. Various vasodilators. such as nitric oxide and calcitonin gene-related peptide, are among candidates in the vasodilatation and the increased arterial compliance recently described in advanced cirrhosis. Reflex-induced enhanced sympatho-adrenal activity, activation of the renin-angiotensin-aldosterone system, and elevated circulating vasopressin and endothelin-1 are implicated in the haemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the haemodynamic and neurohumoral abnormalities in cirrhosis are part of a general cardiovascular dysfunction influencing the course of the disease, with reduction of organ function and sodium-water retention as the outcome. These aspects are relevant to therapy.

Blood Circulation↗
PubMed2001

Endoscopic Doppler ultrasound for measurement of azygos blood flow. Validation against thermodilution and assessment of pharmacological effects of terlipressin in portal hypertension.

BACKGROUND: Endoscopic ultrasound (EUS) is a new modality allowing real-time flow measurements by means of the Doppler technique. The aim of the study was to evaluate azygos blood flow measurements by endoscopic ultrasound. METHODS: Measurements of azygos blood flow by EUS and by the thermodilution technique were compared in 20 patients with portal hypertension. The ability of EUS flowmetry to detect changes in the azygos and portal venous flow after an intravenous dose of 2 mg of terlipressin was evaluated in 13 of the patients in a double-blind, randomized, placebo-controlled, cross-over design. RESULTS: The EUS Doppler and thermodilution measurements correlated significantly (R=0.81, P < 0.001). The azygos blood flow was found to be 14% higher by the EUS method than by thermodilution. The coefficient of variation of the EUS Doppler measurements of the azygos blood flow was 14.8%. After administration of terlipressin, the azygos blood flow, as measured by EUS Doppler, decreased significantly by 23% from 915 to 704 ml/min (P = 0.014) and the portal venous flow decreased by 28% from 1170 to 789 ml/min (P = 0.03). No effects of placebo were detected. CONCLUSIONS: These results show that EUS measurement of the azygos blood flow correlate strongly to the measurements by the thermodilution technique, and EUS is moreover well tolerated by the patients. The method is applicable for monitoring pharmacological effects on the superior porto-systemic collateral circulation and portal venous flow in patients with portal hypertension.

Adult↗
PubMed2001

Effect of beta-adrenergic blockade on elevated arterial compliance and low systemic vascular resistance in cirrhosis.

BACKGROUND: Patients with cirrhosis exhibit a characteristic hyperdynamic circulation with increased cardiac output and heart rate and reduced systemic vascular resistance. The compliance of the arterial tree has recently been reported to be increased in these patients, who are often treated with beta-blockers, but the effect of this treatment on arterial compliance has not been investigated. The aim of the present study was therefore to assess the effects of propranolol on the arterial compliance of patients with cirrhosis. METHODS: Twenty patients with cirrhosis underwent a haemodynamic investigation with determination of splanchnic and systemic haemodynamics. Arterial compliance was determined as the ratio of the stroke volume to the pulse pressure and compared to normal values. RESULTS: All the patients had significant portal hypertension, with a mean hepatic venous pressure gradient (HVPG) of 17.8 mmHg, and responded to beta-blocker treatment with a significant reduction in the HVPG (-16%; P < 0.001). Arterial compliance was elevated (1.27 versus controls 1.01 ml/mmHg; P < 0.001), but remained almost unchanged during beta-adrenergic blockade (1.27 versus 1.29 ml/mmHg, +2%, ns), whereas systemic vascular resistance increased substantially (1083 versus 1378 dyn x s x cm-5, +27%; P < 0.001). The mean arterial blood pressure (-6%; P < 0.05), heart rate (-20%; P < 0.001), cardiac output (-25%; P < 0.001) and hepatic blood flow (-22%; P < 0.001) fell significantly. CONCLUSIONS: Treatment with beta-blockers increases small vessel (arteriolar) vascular tone towards the normal level, but does not affect the elevated compliance of the larger arteries in patients with cirrhosis.

Adrenergic beta-Antagonists↗
PubMed2001

High arterial compliance in cirrhosis is related to low adrenaline and elevated circulating calcitonin gene related peptide but not to activated vasoconstrictor systems.

BACKGROUND AND AIMS: Static and dynamic functions of the wall of large arteries are largely unknown in cirrhosis in vivo. The present study was undertaken to determine arterial compliance (COMP(art)) in relation to vasodilator and vasoconstrictor systems in patients with cirrhosis. In addition, vasoactivity was manipulated by inhalation of oxygen. STUDY POPULATION AND METHODS: In 20 patients with alcoholic cirrhosis and 12 controls we determined COMP(art) (stroke volume relative to pulse pressure), cardiac output, plasma volume, systemic vascular resistance, central circulation time, plasma catecholamines, renin activity, endothelin-1, and calcitonin gene related peptide (CGRP) at baseline and during oxygen inhalation. RESULTS: COMP(art) was significantly increased in cirrhotic patients compared with controls (1.32 v 1.06 ml/mm Hg; p< 0.05) and inversely related to plasma adrenaline levels (r=-0.53; p<0.02) but positively related to circulating levels of CGRP (r=0.58; p<0.01). No significant relation was found for plasma noradrenaline, renin activity, or endothelin-1. COMP(art) was positively related to plasma volume (r=0.50; p<0.02) and inversely to systemic vascular resistance (r=-0.69; p<0.001) and central circulation time (r=-0.49; p<0.02). During oxygen inhalation, COMP(art) decreased (-13%; p<0.005) and systemic vascular resistance increased (+10%; p<0.001) towards normal values without significant changes in mean arterial pressure. Plasma adrenaline (-16%; p<0.01) decreased and the relation to COMP(art) disappeared. The relation of COMP(art) to CGRP and circulatory variables remained unchanged. CONCLUSION: Elevated arterial compliance in cirrhosis is related to low adrenaline, high CGRP, and systemic hyperdynamics but not to indicators of the activated vasoconstrictor systems (noradrenaline, renin, endothelin-1). Thus the altered static and dynamic characteristics of the wall of large arteries are intimately associated with circulatory and vasodilatory derangement in cirrhosis but biomanipulation indicates that the changes are, at least in part, reversible during isobaric conditions.

Adult↗
PubMed2001

Arterial compliance in patients with cirrhosis: stroke volume-pulse pressure ratio as simplified index.

Arterial function may be altered in patients with cirrhosis. We determined compliance of the arterial tree (C(1)) in relation to systemic and splanchnic hemodynamic derangement and clinical variables. C(1) and the stroke volume-pulse pressure index (SV/PP) were significantly higher (+62% and +40%, respectively; P < 0.001) in cirrhotic patients (n = 49) than in control subjects (n = 19), and a close correlation between C(1) and SV/PP was found in both cirrhotic patients (r = 0.86, P < 0.001) and control subjects (r = 0.96, P < 0.001). Univariate analysis showed significant relations between C(1) and SV/PP on one side and age, sex, body weight, portal pressure, systemic hemodynamics, biochemical variables, and severity of disease on the other. In the multiple-regression analysis, sex, age, mean arterial blood pressure, systemic vascular resistance, and biochemical variables were significant independent predictors of SV/PP (P < 0.005-0.00001). In conclusion, arterial compliance is elevated in cirrhosis. A simplified SV/PP index seems to reflect abnormalities in the arterial compliance of these patients.

Algorithms↗
PubMed2001

Splanchnic and systemic hemodynamic derangement in decompensated cirrhosis.

Patients with cirrhosis and portal hypertension exhibit characteristic hemodynamic changes with hyperkinetic systemic circulation, abnormal distribution of blood volume and neurohumoral dysregulation. Their plasma and noncentral blood volumes are increased. Splanchnic vasodilation is of pathogenic significance to the low systemic vascular resistance and abnormal volume distribution of blood, which are important elements in the development of the concomitant cardiac dysfunction, recently termed 'cirrhotic cardiomyopathy'. Systolic and diastolic functions are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms are reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling and conductance abnormalities. Vasodilators such as nitric oxide and calcitonin gene-related peptide are among the candidates in vasodilation and increased arterial compliance. Reflex-induced, enhanced sympathetic nervous system activity, activation of the renin-angiotensin aldosterone system, and elevated circulation vasopressin and endothelin-1 are implicated in hemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the hemodynamic and neurohumoral abnormalities in cirrhosis are part of a general cardiovascular dysfunction, influencing the course of the disease with the reduction of organ function, with sodium and water retention as the outcome. These aspects are relevant to therapy.

Coronary Circulation↗
PubMed2000

Increased circulating calcitonin in cirrhosis. Relation to severity of disease and calcitonin gene-related peptide.

Increased circulating levels of the neuropeptide calcitonin gene-related peptide (CGRP) have recently been described in cirrhosis. CGRP is formed by alternative transcription of the calcitonin/alpha-CGRP gene, which also gives rise to calcitonin (CT). This study was undertaken to determine circulating plasma concentrations of CT in patients with cirrhosis in relation to the severity of disease and the plasma level of CGRP. Moreover, the kinetics of CT was evaluated for different organ systems by determination of arteriovenous extraction. Thirty-nine patients with cirrhosis (Child-Turcotte classes A/B/C, n = 10/22/7) were studied under a hemodynamic investigation and compared with 13 control subjects without liver disease. CT and CGRP in arterial and organ venous plasma were determined by radioimmunoassays. In patients with cirrhosis, circulating CT was significantly increased versus control (12.1 v 6.9 pmol/L, P < .001) and a direct relation to the Child-Turcotte score was found (P < .005). The increased circulating CT was directly correlated with increased CGRP (r = .29, P < .05). No significant arteriovenous extraction of circulating CT was observed in the kidneys, hepatosplanchnic system, lower extremities, or peripheral circulation, but there was a substantial rate of pulmonary disposal and clearance (P < .005). It is concluded that in addition to thyroid production, increased circulating CT in cirrhosis is most likely due to overexpression of the calcitonin/alpha-CGRP gene, with relation to the severity of disease and possibly to an accompanying pulmonary dysfunction.

Adult↗
PubMed2000

Serum YKL-40 is increased in patients with hepatic fibrosis.

BACKGROUND/AIMS: YKL-40, a mammalian member of the chitinase family, is a lectin that binds heparin and chitin. The function of YKL-40 is unknown, but it may function in tissue remodelling. The aims of this study were to assess the level of circulating YKL-40 in patients with various kinds and degree of chronic liver disease and its possible relation to liver fibrosis. METHODS: Serum YKL-40 levels were determined by radioimmunoassay in 129 patients with suspected liver disease and related to histological findings and immunohistochemical staining of YKL-40 in a liver biopsy taken simultaneously with the blood sample. RESULTS: The median serum YKL-40 was highest in patients with alcoholic cirrhosis (532 microg/l), in particular in patients with additional alcoholic hepatitis (740 microg/l). Patients with alcoholic cirrhosis, post-hepatitic cirrhosis (425 microg/l) and non-cirrhotic fibrosis (330 microg/l) had significantly higher serum YKL-40 than normal subjects (102 microg/l), patients with fatty liver (195 microg/l) or patients with viral hepatitis without fibrosis (174 microg/l). Serum YKL-40 was significantly (p<0.001) related to the degree of liver fibrosis with the highest levels in patients with moderate (466 microg/l) to severe (676 microg/l) fibrosis. Serum YKL-40 was also increased (p=0.018) in patients with slight fibrosis (270 microg/l) compared to patients without fibrosis. Immunohistochemical analysis demonstrated positive staining for YKL-40 antigen in areas with fibrosis, particularly areas with active fibrogenesis. YKL-40 staining was never found in hepatocytes. CONCLUSIONS: Our study indicates that the increased serum YKL-40 in patients with liver disease of various degree and aetiology seems to reflect fibrosis and fibrogenesis.

Adipokines↗
PubMed2000

The acid-labile subunit of the ternary insulin-like growth factor complex in cirrhosis: relation to liver dysfunction.

BACKGROUND/AIMS: In the circulation, insulin-like growth factor-I (IGF-I) is bound in a trimeric complex of 150 kDa with IGF binding protein-3 (IGFBP-3) and the acid-labile subunit (ALS). Whereas circulating IGF-I and IGFBP-3 are reported to be low in patients with chronic liver failure, the level of ALS has not been described in relation to hepatic dysfunction. The aim of the present study was therefore to measure circulating and hepatic venous concentrations of ALS in relation to hepatic function and the IGF axis. METHODS: Twenty-five patients with cirrhosis (Child class A/B/C:5/10/10) and 30 controls with normal liver function were studied. During a haemodynamic investigation, blood samples were collected from the hepatic vein and femoral artery, and the plasma concentrations of ALS, IGF-I and IGFBP-3 were determined. RESULTS: Hepatic venous and arterial concentrations of ALS were significantly decreased in the cirrhotic patients compared with the controls (-69% and -68%, respectively, both p<0.001). IGF-I and IGFBP-3 were similarly decreased in the cirrhotic patients (-51%,p<0.001). A significant hepatic extraction of ALS was found in the controls (6%, p<0.01) and in the cirrhotic patients (8%, p=0.08). ALS correlated significantly with indicators of liver dysfunction, including the Child-Turcotte score (r=-0.69, p<0.0001), IGF-I (r=0.82, p<0.0001) and IGFBP-3 (r=0.74, p<0.0001). CONCLUSIONS: Circulating and hepatic venous ALS are decreased in patients with cirrhosis with significant relations to liver dysfunction and other components of the IGF complex. A small hepatic extraction was found in controls, which suggests extrahepatic production of ALS. Future studies should focus on organ-specific removal of ALS.

Adult↗
PubMed2000

Central and systemic haemodynamic effects of terlipressin in portal hypertensive patients.

AIMS/BACKGROUND: Cirrhotic patients exhibit a hyperdynamic and hyporeactive circulation with central hypovolaemia which may influence the course of the disease. As terlipressin, a vasopressin analogue, may modify systemic haemodynamics in these patients, the aim of the present study was to assess the acute effects of terlipressin on central and systemic haemodynamics. METHODS: Sixteen patients with alcoholic cirrhosis and portal hypertension had their systemic, central, and splanchnic haemodynamics determined at baseline and after a blind randomised bolus infusion (2 mg) of terlipressin/placebo. RESULTS: After terlipressin, the arterial blood pressure and the systemic vascular resistance increased by 26% and 61%, respectively (both p<0.001), and the cardiac output, heart rate, and arterial compliance decreased by 18%, 11%, and 32%, respectively (all p<0.001). The central circulation time increased by 36% (p<0.001), whereas the central and arterial blood volume only increased by 4% (p= 0.07). As expected, both portal pressure and hepatic blood flow decreased (17% and 29%, both p<0.001). The decrease in portal pressure after terlipressin was significantly related to the increase in systemic vascular resistance (r=-0.52, p<0.05) and the central circulation time (r=-0.80, p<0.0001). CONCLUSIONS: Terlipressin significantly attenuates the hyperdynamic circulation in portal hypertensive patients without a further contraction of the central and arterial blood volume. The systemic haemodynamic response to terlipressin is moreover associated with the decrease in portal pressure. Terlipressin may therefore have potentially beneficial effects on the hyperdynamic circulation in cirrhosis in addition to its effects on portal pressure.

Adult↗
PubMed2000

Secretin, its discovery, and the introduction of the hormone concept.

The English physician E. H. Starling discovered in collaboration with the physiologist W. M. Bayliss secretin, the first hormone, in 1902. Three years later they introduced the hormone concept with recognition of chemical regulation, early regulatory physiology took a major step forward. The isolation and subsequent synthesis of secretin in the 1960s prepared the way for immunological techniques. Radioimmuno assays in the 1970s enabled demonstration of a direct endocrine role of secretin. Cloning and molecular hybridisation in the 1990s identified production site structure, precursor and evolutionary relation to other gastrointestinal peptides and to the secretin receptor. Although secretin was the first substance to be established as a hormone, even today our understanding is far from complete.

Amino Acid Sequence↗
PubMed2000

Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure.

BACKGROUND/AIMS: C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is considered to be involved in the regulation of vascular tone. Furthermore, the recent demonstration of CNP in human kidney and urine may indicate a role for CNP in fluid and electrolyte homeostasis. Therefore, the aim of the present study was to investigate the possible role of CNP in renal function disturbances in patients with cirrhosis of the liver. METHODS: Peripheral venous and urinary concentrations of CNP were determined in samples from 11 healthy controls, 20 cirrhotic patients with normal renal function (creatinine clearance 117 (8) ml/min), and 20 cirrhotic patients with impaired renal function (creatinine clearance 35 (4) ml/min). In a second protocol, arterial and renal venous plasma concentrations of CNP were determined in 37 patients with cirrhosis of the liver to estimate renal extraction ratios of CNP. A sensitive and specific radioimmunoassay was applied after solid phase extraction of samples. RESULTS: Plasma CNP was lower in cirrhotic patients with normal and impaired renal function than in controls (3.0 (0.4) and 2.7 (0.2) v. 4.2 (0.4) pg/ml, respectively; p<0.05; mean (SEM)). In contrast, urinary CNP was higher in patients with impaired renal function compared with those with normal renal function and healthy controls (47.2 (7.4) v. 20.8 (1.9) and 17.0 (3.0) ng CNP/g creatinine, respectively; p<0.05). Urinary CNP was found to be inversely related to urinary sodium excretion in cirrhotic patients (r=-0.56; p<0.01). No differences were observed between arterial and renal venous concentrations of CNP in cirrhosis (2.4 (0.2) v. 2.4 (0.2) pg/ml). In cirrhotic patients with hepatorenal syndrome or refractory ascites (n=5), urinary CNP decreased from 132 (59) to 38 (7) ng/g creatinine (p<0.05) one week after either ornipressin infusion or insertion of a transjugular intrahepatic portosystemic shunt together with an increase in urinary sodium excretion from 27 (17) to 90 (34) mmol/24 hours. CONCLUSIONS: Increased urinary CNP in cirrhotic patients in the absence of renal arteriovenous concentration gradients suggests enhanced renal CNP production in cirrhosis. Furthermore, an inverse relation between urinary CNP and urinary sodium excretion suggests a role for this peptide in renal sodium handling in patients with cirrhosis.

Analysis of Variance↗