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Biomedical subjects

V Gülberg

Publications and source records attributed to V Gülberg.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

Hepatic blood flow and splanchnic oxygen consumption in patients with liver failure. Effect of high-volume plasmapheresis.

Liver failure represents a major therapeutic challenge, and yet basic pathophysiological questions about hepatic perfusion and oxygenation in this condition have been poorly investigated. In this study, hepatic blood flow (HBF) and splanchnic oxygen delivery (DO2, sp) and oxygen consumption (VO2,sp) were assessed in patients with liver failure defined as hepatic encephalopathy grade II or more. Measurements were repeated after high-volume plasmapheresis (HVP) with exchange of 8 to 10 L of plasma. HBF was estimated by use of constant infusion of D-sorbitol and calculated according to Fick's principle from peripheral artery and hepatic vein concentrations. In 14 patients with acute liver failure (ALF), HBF (1.78 +/- 0.78 L/min) and VO2,sp (3.9 +/- 0.9 mmol/min) were higher than in 11 patients without liver disease (1.07 +/- 0.19 L/min, P <.01) and (2.3 +/- 0.7 mmol/min, P <.001). In 9 patients with acute on chronic liver disease (AOCLD), HBF (1.96 +/- 1.19 L/min) and VO2,sp (3.9 +/- 2.3 mmol/min) were higher than in 18 patients with stable cirrhosis (1.00 +/- 0.36 L/min, P <.005; and 2.0 +/- 0.6 mmol/min, P <.005). During HVP, HBF increased from 1.67 +/- 0.72 to 2.07 +/- 1.11 L/min (n=11) in ALF, and from 1.89 +/- 1.32 to 2.34 +/- 1.54 L/min (n=7) in AOCLD, P <.05 in both cases. In patients with ALF, cardiac output (thermodilution) was unchanged (6.7 +/- 2.5 vs. 6.6 +/- 2.2 L/min, NS) during HVP. Blood flow was redirected to the liver as the systemic vascular resistance index increased (1,587 +/- 650 vs. 2, 020 +/- 806 Dyne. s. cm-5. m2, P <.01) whereas splanchnic vascular resistance was unchanged. In AOCLD, neither systemic nor splanchnic vascular resistance was affected by HVP, but as cardiac output increased from 9.1 +/- 2.8 to 10.1 +/- 2.9 L/min (P <.01) more blood was directed to the splanchnic region. In all liver failure patients treated with HVP (n=18), DO2,sp increased by 15% (P <.05) whereas VO2,sp was unchanged. Endothelin-1 (ET-1) and ET-3 were determined before and after HVP. Changes of ET-1 were positively correlated with changes in HBF (P <.005) and VO2,sp (P <.05), indicating a role for ET-1 in splanchnic circulation and oxygenation. ET-3 was negatively correlated with systemic vascular resistance index before HVP (P <.05) but changes during HVP did not correlate. Our data suggest that liver failure is associated with increased HBF and VO2, sp. HVP further increased HBF and DO2,sp but VO2,sp was unchanged, indicating that splanchnic hypoxia was not present.

Acute Disease↗
PubMed1999

Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamine.

Peripheral vasodilation is considered an important factor in the pathophysiology of the hepatorenal syndrome (HRS). Therefore, the aim of this study was to evaluate the therapeutic potential of the vasoconstrictor ornipressin plus dopamine in the treatment of the most severe form of HRS, namely HRS type 1. Seven cirrhotic patients (creatinine clearance 15 +/- 1 mL/min, UNaV 7 +/- 2 mmol/24 h) with HRS type 1 were included in the study after normalization of central venous pressure with intravenous albumin and low-dose dopamine had failed to prevent further deterioration of renal function. Ornipressin was given continuously (intravenous 6 IU/h) in combination with dopamine (2-3 microgram/kg/min) until creatinine clearance had increased to above 40 mL/min or adverse events prevented further treatment. HRS was reverted in 4 of 7 patients after 5 to 27 days (creatinine clearance 51 +/- 4 mL/min, UNaV 47 +/- 11 mmol/24 h) of treatment. Withdrawal was necessary in 1 patient after 15 days because of intestinal ischemia. Treatment failure was observed in 2 of 7 patients (creatinine clearance 19 +/- 10 mL/min, UNaV 8 +/- 3 mmol/24 h). Two of 4 responders had recidivant HRS 2 and 8 months after initial therapy, respectively. HRS in 1 of these patients was reverted with 18 days of ornipressin retreatment. The other patient had to be withdrawn from ornipressin after 2 hours because of ventricular tachyarrhythmia. Altogether, 3 of 7 patients survived HRS type 1, 1 after successful ornipressin therapy and liver transplantation, 1 with 2 successful courses of ornipressin, and 1 with liver transplantation after ornipressin treatment had failed. Thus, ornipressin plus dopamine can be a useful therapeutic option in patients with HRS type 1, especially as bridge to liver transplantation.

Dopamine↗
PubMed1998

Renal effects of transjugular intrahepatic portosystemic shunt in cirrhosis: comparison of patients with ascites, with refractory ascites, or without ascites.

Renal effects of the transjugular intrahepatic portosystemic shunt (TIPS) were compared in 6 patients without ascites (group 1), 11 patients with ascites responding to diuretic treatment (group 2), and 6 patients with refractory ascites (group 3). Seven days after insertion of TIPS, 24-hour urinary sodium excretion had increased in patients with ascites: 113 +/- 16 mmol to 170 +/- 30 mmol (P = .012) in group 2, and 22 +/- 8 mmol to 77 +/- 27 mmol (P = .050) in group 3. In group 3, fractional sodium excretion tended to increase from 0.26% +/- 0.14% to 0.62% +/- 18% (P = .081). The relative increase of urinary sodium excretion (to 444% +/- 122%) and fractional sodium excretion (to 413% +/- 127%) in group 3 was significantly (P < .05) higher than in group 1 and group 2, respectively. Creatinine clearance and 24-hour urinary volume were not significantly changed in either group. Patients with Child-Pugh class C had a more pronounced effect of TIPS on urinary sodium excretion (increase to 396% +/- 115% vs. 139% +/- 15%; P = .066) and on fractional sodium excretion (increase to 415% +/- 103% vs. 94% +/- 15%; P = .020) than patients with less-severe liver disease. Fractional sodium excretion of less than 0.35% before TIPS was found to be an indicator of renal response to TIPS. The effect of TIPS on urinary sodium excretion and on fractional sodium excretion was related to the patients' Child-Pugh score (r = .55; P = .007 and r = .68; P = .001, respectively) and inversely to their fractional sodium excretion (r = -.44; P = .047 and r = -.54; P = .012, respectively) before TIPS. These data demonstrate that TIPS affects renal sodium handling in patients with ascites, particularly in patients with refractory ascites. Severity of liver disease and fractional sodium excretion before TIPS are parameters to predict the extent of the renal response.

Adult↗
PubMed1998

Transjugular intrahepatic portosystemic shunt (TIPS) for variceal bleeding in portal hypertension: comparison of emergency and elective interventions.

Nonsurgical reduction of portal hypertension by transjugular intrahepatic portosystemic shunt (TIPS) is widely used for prevention of variceal rebleeding (elective TIPS). Information is limited about the value of emergency TIPS for acute variceal bleeding unresponsive to endoscopic and drug therapy. The aim of the present study was therefore to determine whether the effects and complications differ between emergency and elective TIPS in patients with cirrhosis of the liver. TIPS was performed in 11 patients with acute variceal bleeding unresponsive to endoscopic treatment and 22 patients in stable condition after an episode of variceal bleeding. Clinical examination, blood sampling, Doppler sonography of TIPS flow, and upper gastrointestinal endoscopy were performed at days 1, 7, and 30 and at three-month intervals after TIPS. Mean follow-up was 549 (1-987) days. Bleeding was controlled by emergency TIPS in 10/11 patients. Probability of survival was not different after emergency and elective TIPS (0.73 vs 0.84 at one year). Early rebleeding (< or =2 weeks) occurred more often after emergency TIPS (3/11 vs 0/22 patients; P = 0.03), but there was no significant difference in late rebleeding. Occlusion of TIPS was more frequent after emergency TIPS. Occurrence of TIPS stenoses was identical in both groups (4/11 vs 8/22). De novo or deterioration of preexisting hepatic encephalopathy was similar (18% vs 24%; NS). It is concluded that TIPS is effective for control of acute variceal bleeding unresponsive to endoscopic and drug treatment. Early rebleeding and stent occlusion occurred more often after emergency TIPS. Late rebleeding, complications, and long-term survival did not differ from elective TIPS.

Acute Disease↗
PubMed1998

[Successful conservative therapy of hepatorenal syndrome with vasopressin-1-receptor antagonist ornipressin].

A 47-year-old male patient with alcoholic cirrhosis Child-Pugh grade C was admitted to our center for evaluation of liver transplantation. Serum creatinine had increased from 1.6 to 4.3 mg/100 ml within the previous two weeks, creatinine clearance was 12 ml/min, and urinary sodium 12 mmol/24 h. The diagnosis of HRS type I was established. Diuretic treatment was discontinued. Following albumin infusion, central venous pressure was increased to above 10 cm H2O and dopamine (2 micrograms/kg/min) infusion was started. However, renal function did not improve. An i.v. infusion of ornipressin (POR8, Sandoz; 6 IU/h) was started and dopamine infusion continued. During a four-hour interval, urinary volume and sodium excretion doubled. Therefore treatment was continued for three weeks. After 22 days, renal function had normalized (creatinine 1.2 mg/100 ml, creatinine clearance 65 ml/min, urinary sodium 62 mmol/24 h) and diuretic therapy was resumed. No adverse effects were observed. Ornipressin/dopamine infusion was discontinued and renal function remained normal. Three weeks later, the patient underwent liver transplantation with normal renal function. Ornipressin infusion had no effect on circulating endothelin, but decreased the activation of the renin-aldosterone system and of the sympathetic activity. So far, no noninvasive therapy of hepatorenal syndrome has been established. This is the first report of successful medical treatment of HRS type I with a three-week infusion of the vasopressin-l-receptor agonist ornipressin.

Dose-Response Relationship, Drug↗
PubMed1998

Experiences with novel techniques for reduction of stent flow in transjugular intrahepatic portosystemic shunts.

The transjugular intrahepatic portosystemic shunt (TIPS) may deteriorate liver function and can cause encephalopathy in patients with cirrhosis of the liver. Then reduction of TIPS flow may be required. We here report several attempts to reduce shunt flow in TIPS-induced encephalopathy or liver function impairment with novel techniques. Three patients with cirrhosis of the liver were investigated: Two with severe recurrent encephalopathy and one with impaired liver function following TIPS insertion. Insertion of a reducing stent was ineffective to decrease shunt flow velocity in one patient with severe coagulopathy. Sufficient reduction of shunt flow was achieved by embolizing the space around the hourglass waist of the reducing stent with an occlusion emulsion. Insertion of a conventional stent within the preexisting TIPS with or without additional embolization reduced TIPS flow in the other patients. After reduction of shunt flow encephalopathy improved and liver function returned to the level before TIPS, respectively. During follow-up no occlusion of TIPS was observed. Thus, reduction of shunt flow velocity can be achieved by insertion of an additional stent into a curve-shaped TIPS. Embolization can be helpful to decrease TIPS flow, particularly in patients with severe coagulopathy. Reduction of TIPS flow can correct TIPS-induced complications.

Blood Flow Velocity↗
PubMed1997

Daily profile of plasma endothelin-1 and -3 in pre-ascitic cirrhosis: relationships with the arterial pressure and renal function.

BACKGROUND/AIMS: Measurements of plasma endothelin-1 and -3 in pre-ascitic cirrhosis have provided controversial results. Similarly, the role of the endothelin system in the pathogenesis of volume and hemodynamic disturbances of cirrhosis is still debated. To provide a further insight into this issue, we assessed the daily fluctuations of plasma endothelins and their relationship with arterial pressure and renal function in pre-ascitic cirrhosis. METHODS: Endothelin-1 and -3, plasma renin activity, atrial natriuretic peptide, noradrenaline and mean arterial pressure were measured at 11 pm, 7 am, 9 am and 6 pm in 10 patients with pre-ascitic cirrhosis and in 10 healthy subjects on normal sodium diet and carrying on their usual activities (supine from 10 pm to 7 am, standing and mobile after 7 am). Glomerular filtration rate and daily renal sodium excretion were assessed during the supine period, and from 7 am to 12 am and from 12 am to 10 pm during the standing period. RESULTS: Endothelin-1 was higher in patients than in control subjects (p=0.000) and did not change during the study. Endothelin-3 was also higher in patients (p=0.002) and showed slight fluctuation in control subjects. The mean daily level of plasma renin activity was lower (p=0.016) and that of atrial natriuretic peptide higher (p=0.000) in patients with cirrhosis. Norepinephrine and mean arterial pressure did not differ significantly between the two groups. No correlations were found between endothelins and either hemodynamic or neuro-hormonal and renal function parameters in the two groups. CONCLUSIONS: Despite the presence of increased effective volemia (as suggested by the reduced plasma renin activity and elevated atrial natriuretic peptide) and normal adrenergic tone, patients with pre-ascitic cirrhosis show elevated levels of endothelin-1 and endothelin-3 throughout the day. In early cirrhosis circulating endothelins, although elevated, do not appear to play a more prominent role in setting arterial pressure than in normal subjects, and endothelin elevation is not detrimental to renal function.

Adult↗
PubMed1995

Endothelin-1 and endothelin-3 in cirrhosis: relations to systemic and splanchnic haemodynamics.

BACKGROUND/AIMS: Endothelins are isopeptides with potent vasoactive properties, but their implications in the hyperkinetic syndrome in cirrhosis are obscure. Therefore, the aim of the present study was to relate hepatic venous and circulating endothelin-1 and endothelin-3 to systemic and splanchnic haemodynamics. METHODS: Endothelin-1 and endothelin-3 were measured in samples from a hepatic vein and the femoral artery in 42 patients with cirrhosis, eight hypertensive controls and 10 normotensive controls. RESULTS: Hepatic venous endothelin-1 was significantly higher in the patients with cirrhosis, mean 21.2 +/- 0.9 pg/ml (SEM) than in the hypertensive controls, 12.4 +/- 2.4 pg/ml, and normotensive controls, 9.6 +/- 1.6 pg/ml (p < 0.00001). Similarly arterial endothelin-1 was significantly higher in the patients with cirrhosis than in the controls (p < 0.00001). Hepatic venous endothelin-1 was significantly correlated with the hepatic venous pressure gradient (r = 0.61, p < 0.00004), serum creatinine (r = 0.35, p < 0.03), diastolic blood pressure (r = -0.31, p < 0.05), central and arterial blood volume (-0.36, p < 0.05), central circulation time (r = -0.41, p < 0.02), and serum sodium (r = -0.56, p < 0.00002) in the patients with cirrhosis. The hepatosplanchnic release of endothelin-1, assessed as the arteriohepatic-venous difference adjusted for hepatic plasma flow, was higher in the group with cirrhosis, 1.5 +/- 0.4 ng/min, than in the normotensive controls, -0.1 +/- 0.2 ng/min (p < 0.01), and was furthermore correlated to the cardiac output in the group with cirrhosis (r = 0.35, p < 0.04). Hepatic venous endothelin-3 was higher in the patients with cirrhosis, 19.0 +/- 1.4 pg/ml (n = 23), as compared with hypertensive controls, 14.2 +/- 1.3 pg/ml, and normotensive controls, 10.0 +/- 1.4 pg/ml (p < 0.002). The same pattern was found in arterial endothelin-3. Hepatic venous endothelin-3 correlated significantly with central and arterial blood volume (r = 0.56, p < 0.02). The hepatosplanchnic release of endothelin-3 was higher in the patients with cirrhosis, 1.0 +/- 0.7 ng/min, than in the normotensive controls, -0.7 +/- 0.4 ng/min (p = 0.05). CONCLUSIONS: In the presence of cirrhosis, hepatic venous and circulating endothelin-1 and endothelin-3 are elevated with significant relations to systemic and splanchnic haemodynamics, and the hepatosplanchnic release of both peptides is increased. This suggests that the endothelin system is implicated in both systemic and portal haemodynamic abnormalities in cirrhosis, although this study does not allow conclusions on causal relationships.

Adult↗
PubMed1995

Relation of endothelins to volume regulating neurohumoral systems in patients with cirrhosis of the liver.

The aim of the present study was to investigate the relationship between ET plasma concentrations and other hormonal systems in acute volume regulation of patients with cirrhosis. Ten healthy controls and 10 cirrhotic patients, five without and five with ascites were studied after 1 h in a sitting posture and subsequently subjected to 1 h head-out water immersion. Blood was collected for determinations of ET-1, ET-3, ANF, aldosterone, renin activity and noradrenaline. In addition, in 10 patients with compensated cirrhosis the effect of loop diuretics on ET-3, aldosterone and renin was studied. ETs in cirrhosis were significantly (P < 0.01) higher than in controls both before (ET-1, 19.6 +/- 1.3 pgmL-1 vs. 11.8 +/- 0.4 pgmL-1; ET-3, 18.5 +/- 1.4 pgmL-1 vs. 9.5 +/- 0.5 pgmL-1) and after water immersion (ET-1, 18.6 +/- 1.2 pgmL-1 vs. 12.4 +/- 0.3 pgmL-1; ET-3, 18.7 +/- 1.7 pgmL-1 vs. 10.0 +/- 0.5 pgmL-1). In cirrhotic patients, basal and immersion concentrations of ET-1 were significantly correlated to noradrenaline plasma concentrations (r = 0.79, P < 0.05). ET-3 plasma concentrations in cirrhosis were correlated to renin activity (r = 0.65, P < 0.05). Furthermore, ET-3 in cirrhosis was inversely correlated to systolic and mean arterial blood pressure (r = -0.55, P < 0.01 and r = -0.50, P < 0.05; respectively). To investigate the effect of hypovolaemia in compensated cirrhosis, 10 patients without ascites were studied before and after treatment with loop diuretics. In compensated cirrhosis ET-3 was significantly increased 6h after oral diuretic treatment (17.9 +/- 1.0 pgmL-1 vs. 15.5 +/- 0.4 pgmL-1, P < 0.001). The presented data demonstrate relations of endothelins, particularly of ET-3 to neurohumoral systems in patients with cirrhosis of the liver.

Adult↗
PubMed1995

Endothelin-1 and -3 plasma concentrations in patients with cirrhosis: role of splanchnic and renal passage and liver function.

Increased as well as decreased plasma concentrations of the endothelins, endogenous vasoactive peptides, have been reported in cirrhosis. This might be caused by alterations of hepatic or renal clearance or release. Therefore, the aim of the current study was to investigate the influence of splanchnic and renal passage and of liver function on plasma concentrations of endothelin-1 (ET-1) and endothelin-3 (ET-3) in patients with cirrhosis compared with controls. Eighteen patients with cirrhosis and 8 normotensive controls of similar age were investigated. Arterial and venous plasma samples were obtained simultaneously, and ET-1 and ET-3 concentrations were determined in extracted plasma by two separate radioimmunoassays. Arterial as well as hepatic and renal venous concentrations of ET-1 in cirrhosis (17.8 +/- 0.8 pg/mL, 19.1 +/- 0.9 pg/mL, and 16.8 +/- 0.8 pg/mL) were significantly (P < .001) higher than in controls (9.2 +/- 1.7 pg/mL, 9.0 +/- 2.0 pg/mL, and 8.4 +/- 1.9 pg/mL, respectively). The same held true for the corresponding ET-3 plasma concentrations in cirrhosis (19.3 +/- 1.6 pg/mL, 20.5 +/- 1.5 pg/mL, and 18.4 +/- 1.5 pg/mL, respectively) compared with controls (11.1 +/- 1.8 pg/mL, 11.3 +/- 1.5 pg/mL, and 10.1 +/- 1.7 pg/mL, respectively; P < .01). There was a significant (P < .05) renal net extraction of ET-1 and ET-3 in cirrhosis. In contrast, a significant (P < .05) net release of ET-1 and ET-3 (2.40 +/- 0.80 ng/min and 1.75 +/- 1.16 ng/min) during splanchnic passage was observed in cirrhosis, but not in controls (-0.24 +/- 0.51 ng/min, and -0.46 +/- 0.64 ng/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Endothelin-1 and endothelin-3 in the plasma of dogs].

The endothelins represent a family of peptides with potent vasoconstrictory effects indicating a role in the regulation of vascular tone. An involvement of endothelins in the pathogenesis as well as pathophysiology of vascular diseases has been proposed. Therefore, the aim of the presented study was to develop the methodology to measure and characterize endothelin-1 (ET-1) and endothelin-3 (ET-3) in the plasma of dogs. Extraction of acidified plasma samples was performed by use of Sep-Pak C18 cartridges and plasma levels of ET-1- and ET-3-immunoreactivity (ET-1-IR; ET-3-IR) were determined by specific radioimmunoassays. The measured ET-immunoreactivities were verified by separation of plasma using high-pressure liquid chromatography (HPLC).

Amino Acid Sequence↗