Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of a somatostatin analogue, SMS 201-995 on hepatic haemodynamics were studied in rats with dimethylnitrosamine-induced cirrhosis. An intravenous infusion of 1, 2 or 4 micrograms kg-1 body wt h-1 SMS 201-995 produced a rapid and sustained decrease in portal pressure, portal venous flow and liver blood flow without significantly altering arterial blood pressure or pulse. The reductions in portal pressure, portal venous flow and liver blood were accompanied by an increase in splanchnic vascular resistance. Portal venous resistance was not affected. Subcutaneous injection of 2 micrograms kg-1 body wt SMS 201-995 produced a gradual decrease in portal pressure, the maximum reduction occurring 18 min after administration. This reduction in portal pressure was sustained for a further 20 min. The results suggest that SMS 201-995 may be of value in the control of bleeding oesophageal varices. Furthermore, the prolonged duration of action of SMS 201-995 following its subcutaneous administration suggests that the analogue may be useful in the long-term management of portal hypertension in patients with cirrhosis.
 ...
PMID:The effects of a somatostatin analogue SMS 201-995 on hepatic haemodynamics in the cirrhotic rat. 286 12

The effects of a long acting somatostatin analogue, SMS 201-995, on reticulo-endothelial system (RES) activity were studied in rats. Administration of 2 micrograms SMS 201-995 subcutaneously twice a day for 7 days significantly increased the splenic and hepatic uptake of 99mTc-sulphur colloid and damaged 51mCr-red blood cells. Furthermore, SMS 201-995 administration significantly increased the plasma clearance of colloidal carbon as indicated by a lower area under the curve and an increased elimination constant. SMS 201-995 administration also significantly improved survival after intraperitoneal injection of Escherichia coli endotoxin. These results suggest that SMS 201-995 stimulates RES activity in rats. It is suggested that SMS 201-995 may be of value in stimulating RES activity in patients with cirrhosis and portal hypertension.
 ...
PMID:Effects of a somatostatin analogue (SMS 201-995) on hepatic and splenic reticulo-endothelial function in the rat. 286 1

The effects of a somatostatin analogue, SMS 201-995, on hepatic haemodynamics in the pig and on intravariceal pressure in man were studied. An infusion of 250 micrograms/h SMS 201-995 significantly reduced portal pressure, portal venous flow and hepatic artery flow in the pig. These changes in hepatic haemodynamics were accompanied by a reduction in cardiac output, a reflex slowing of the heart and an increase in arterial blood pressure. Splanchnic vascular resistance was increased following SMS 201-995 administration but hepatic vascular resistance remained unchanged. Administration of 50 micrograms SMS 201-995 reduced the intravariceal pressure from 27.4 +/- 2.5 to 15.8 +/- 2.1 mmHg in 9 patients with cirrhosis and portal hypertension. Administration of 50 micrograms SMS 201-995 also reduced portal pressure from 29 to 22 mmHg in a patient undergoing an elective portacaval shunt. These results suggest that SMS 201-995 may be of value in the control of bleeding oesophageal varices. Furthermore, because of its prolonged duration of action SMS 201-995 may be useful in the long term management of portal hypertension in patients with cirrhosis.
 ...
PMID:Effects of a somatostatin analogue SMS 201-995 on hepatic haemodynamics in the pig and on intravariceal pressure in man. 286 2

The influence of a long-acting somatostatin octapeptide analogue (SMS 201-995) on splanchnic circulation and metabolism has been studied in healthy subjects and in patients with liver cirrhosis. In healthy subjects doses of 5, 10, 50, or 100 micrograms SMS and in the cirrhotic patients 25 micrograms SMS were infused intravenously during 1 h. Measurements were obtained before, during, and for 1 h after SMS infusion. SMS infusion in healthy subjects resulted in a 25-35% reduction in hepatic blood flow. This effect was largely independent of the dose used. Splanchnic oxygen uptake was unchanged before and during SMS infusion. Insulin and glucagon levels fell markedly in response to SMS administration, and the blood concentration and splanchnic output of glucose decreased transiently. Patients with liver cirrhosis responded to SMS infusion similarly to the healthy subjects. Hepatic blood flow decreased by 25-35% and remained suppressed for at least 1 h after infusion. Wedge hepatic venous pressure was 18 +/- 2 mm Hg in the basal state and decreased progressively during and after SMS infusion (60 min after infusion, 15 +/- 2 mm Hg; P less than 0.01). The marked hyperinsulinaemia and hyperglucagonaemia seen in the basal state decreased significantly during SMS administration. As in the case of the controls, blood concentration and splanchnic output of glucose fell transiently during and after SMS infusion. It is concluded that SMS exerts a marked and prolonged suppressive effect on hepatic blood flow in both healthy subjects and patients with liver cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The influence of a long-acting somatostatin analogue on splanchnic haemodynamics and metabolism in healthy subjects and patients with liver cirrhosis. 287 92

The influence of SMS 201-995 (octreotide, Sandostatin), a long-acting somatostatin analogue, on splanchnic haemodynamics was studied in 15 patients with liver cirrhosis and in 5 healthy individuals before, during, and after 60 min of intravenous SMS infusion (25 and 50 micrograms/h, respectively). No adverse effects of the SMS infusion were seen. In the basal state the estimated hepatic blood flow was 1.04 +/- 0.08 l/min (mean +/- SE) in the patients and 1.62 +/- 0.09 l/min (P less than 0.001) in the controls. At 15 min after the beginning of the infusion the blood flow had already decreased by 15-30% (P less than 0.05-0.01). The reduction was more marked in controls than in patients, and it persisted in both groups during and for 60 min after the infusion. Wedged hepatic venous pressure, measured in the patients, was 20 +/- 2 mmHg in the basal state and 18 +/- 1 mmHg during the infusion (P less than 0.05), and it remained at this level for 60 min after the infusion. Free hepatic venous pressure was unchanged throughout the study. Splanchnic oxygen uptake was similar in the two groups in the basal state and remained unaltered during and after SMS infusion. Both heart rate and arterial systolic and diastolic blood pressure remained unchanged during SMS administration. In summary, SMS infusion results in a fall in hepatic blood flow and a slight but significant decrease in wedged hepatic venous pressure, whereas no effect was noted on the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Haemodynamic effects of a long-acting somatostatin analogue in patients with liver cirrhosis. 289 Nov 84

Somatostatin is present in the gastrointestinal tract in appreciable amounts. The highest concentrations of the polypeptide are found in the stomach, the upper small intestine, and the pancreas. Within the gastrointestinal tract, somatostatin inhibits various functions, including endocrine and exocrine secretion, motility, blood flow, absorption, and growth. The polypeptide regulates these functions by endocrine, paracrine, neurocrine or luminal mechanisms. Abnormalities of endogenous somatostatin have been implicated in several gastrointestinal disorders, including the somatostatinoma syndrome, antroduodenal D-cell hyperplasia, peptic ulcer, obesity, and liver cirrhosis. Because of its potent inhibitory effects, somatostatin or somatostatin-analogues have been used as therapeutic agents in various clinical conditions, such as upper gastrointestinal haemorrhage, endocrine pancreatic tumours, gastrointestinal and pancreatic fistulas, pancreatitis, secretory diarrhoea, and dumping syndrome. The recent availability of the synthetic long-acting somatostatin-analogue SMS 201-995 (Sandostatin) has greatly facilitated the therapeutical application of somatostatin-polypeptides.
 ...
PMID:Clinical and pathophysiological aspects of somatostatin and the gastrointestinal tract. 289 34

Sandostatin (SMS 201-995) was evaluated in the treatment of variceal bleeding in 9 patients with liver cirrhosis and portal hypertension who were undergoing injection sclerotherapy following a variceal haemorrhage. SMS 201-995 reduced directly recorded intravariceal pressure by 38%, whereas reductions in the wedged hepatic venous pressure were around 17%. These observations suggest that SMS 201-995 may prove useful in treating bleeding oesophageal varices in the acute situation. Preliminary, promising data are shown in the results of a randomized controlled clinical trial in which SMS 201-995 plus injection sclerotherapy vs injection sclerotherapy are compared in patients with bleeding oesophageal varices. Furthermore, in experimental work associated stimulating effects of SMS 201-995 are shown on the function of the reticulo-endothelial system both in the liver and peripherally. These effects may prove useful by reducing the effects of endotoxaemia and possibly result in arresting further liver damage.
 ...
PMID:SMS 201-995 and variceal haemorrhage. 289 36

A somatostatin analogue, a long-acting octapeptide (SMS 201-995), has been reported to decrease portal pressure, but the mechanism is unclear. To elucidate the effects of this drug on both systemic and splanchnic hemodynamics, it was administered in two conscious rat models of portal hypertension. The dose-response curves showed that the somatostatin analogue significantly decreased portal pressure at a lower dose in rats with cirrhosis than in portal vein-stenosed rats. Calculated ED50 values were significantly different among all groups. Intravenous infusion of 8 micrograms/kg body wt.h of somatostatin analogue significantly decreased cardiac output by approximately 20% in both groups of portal hypertensive rats and increased mean arterial pressure by 7%. Accordingly, systemic vascular resistance markedly increased, indicating vasoconstrictor effects of this drug. The somatostatin analogue also significantly decreased portal tributary blood flow by 18% in portal vein-stenosed rats and 27% in cirrhotic rats. In sham-operated rats, somatostatin analogue had no effect on the systemic or splanchnic circulation. This study shows that somatostatin analogue decreases portal pressure principally by reducing portal tributary blood flow. This reduction may be due to either a direct vasoconstrictive effect or diminution in vasoactive hormone release.
 ...
PMID:Circulatory effects of somatostatin analogue in two conscious rat models of portal hypertension. 289 52

The effect of the long-acting somatostatin analogue SMS 201-995 on renal function was investigated in nine cirrhotic patients with ascites, low urine output, low serum sodium, and normal serum creatinine. SMS 201-995, infused at 40 micrograms/h for 2 h, produced a significant increase in urine volume, a significant decrease in urine osmolality, and a significant increase in creatinine clearance. These changes, although less pronounced, persisted 24 h after the infusion of the analogue. No significant changes in free water clearance, urinary sodium excretion or serum sodium were noted. The effects of SMS 201-995 might be attributed to an improvement of renal haemodynamics through inhibition of vasoconstrictor systems acting in cirrhosis. It is concluded that SMS 201-995 may have a role in the treatment of the renal abnormalities complicating liver disease.
 ...
PMID:Enhancement of renal function by a long-acting somatostatin analogue in patients with decompensated cirrhosis. 314 15

The authors investigated whether combined treatment with the somatostatin analogue, SMS 201-995, and low-dose isosorbide dinitrate enhanced the hemodynamic effects of the individual agents on rats with thioacetamide-induced cirrhosis. Four groups of cirrhotic rats received SMS 201-995 (0.1 microgram.min-1.kg-1), isosorbide dinitrate (10 micrograms.min-1.kg-1), both agents, or placebo, respectively. Hemodynamics were measured serially in conscious rats, using a radioactive microsphere method. SMS 201-995 reduced portal venous inflow 21 +/- 4% and portal pressure 17 +/- 3%. Isosorbide dinitrate decreased portal venous inflow 20 +/- 4%, by inducing splanchnic vasoconstriction mediated by low pressure baroreflexes, and this agent also decreased portal pressure, by 14 +/- 2%. Portal venous resistance rose 7.6 +/- 3% with isosorbide dinitrate alone, but decreased 18 +/- 4% with combination therapy. This effect may have been induced by the pronounced vasodilatory effect of isosorbide dinitrate on the venous vasculature, since the reflex splanchnic vasoconstriction that occurs with low-dose isosorbide dinitrate disappears when this agent is combined with SMS 201-995. The decrease in portal pressure was more marked (22 +/- 4%) and changes in systemic hemodynamics were milder with the combined treatment. It was concluded that combination therapy with SMS 201-995 and low-dose isosorbide dinitrate may be beneficial for portal hypertension in liver cirrhosis.
 ...
PMID:Hemodynamic effects of combined treatment with somatostatin analogue (SMS 201-995) and low-dose isosorbide dinitrate on portal hypertension in conscious cirrhotic rats. 795 57


1