Literature DB >> 3734100

Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver.

J Reichen, M Le.   

Abstract

The effect of the calcium channel blocking agent, verapamil, on microcirculatory patterns and hepatic function was investigated in the perfused liver of cirrhotic rats. Compared with controls, cirrhotic livers had higher vascular resistance, increased intrahepatic shunting, and smaller extravascular albumin space and larger extravascular sucrose space, as determined by a multiple-indicator dilution technique. Hepatic function, estimated by determining propranolol and antipyrine extraction, was markedly reduced in cirrhotic livers. Portal pressure was then reduced 25% either pharmacologically by verapamil or hydrodynamically by lowering inflow. Verapamil decreased vascular resistance by 22%. This was associated with a 38% reduction in intrahepatic shunting and a 62% increase in extravascular albumin space. Hydrodynamically lowering pressure had no or adverse effects. The verapamil-induced improvement in microcirculatory characteristics was associated with a significant improvement in oxygen consumption (+21%) and antipyrine clearance (+20%). We conclude that the microvascular distortions of liver cirrhosis in the rat are partially reversible by vasodilators like verapamil.

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Year:  1986        PMID: 3734100      PMCID: PMC423578          DOI: 10.1172/JCI112596

Source DB:  PubMed          Journal:  J Clin Invest        ISSN: 0021-9738            Impact factor:   14.808


  51 in total

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Authors:  R A Branch; J A James; A E Read
Journal:  Clin Pharmacol Ther       Date:  1976-07       Impact factor: 6.875

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Authors:  B B BRODIE; J AXELROD
Journal:  J Pharmacol Exp Ther       Date:  1950-01       Impact factor: 4.030

3.  The disposition of propranolol. IV. A dominant role for tissue uptake in the dose-dependent extraction of propranolol by the perfused rat liver.

Authors:  G H Evans; G R Wilkinson; D G Shand
Journal:  J Pharmacol Exp Ther       Date:  1973-09       Impact factor: 4.030

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Authors:  C A Goresky; W H Ziegler; G G Bach
Journal:  Circ Res       Date:  1970-11       Impact factor: 17.367

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Authors:  M Rowland; L Z Benet; G G Graham
Journal:  J Pharmacokinet Biopharm       Date:  1973-04

6.  Instant cirrhosis. An improved method for producing cirrhosis of the liver in rats by simultaneous administration of carbon tetrachloride and phenobarbitone.

Authors:  E K McLean; A E McLean; P M Sutton
Journal:  Br J Exp Pathol       Date:  1969-10

7.  Mechanism for reduced drug clearance in patients with cirrhosis.

Authors:  D Pessayre; D Lebrec; V Descatoire; M Peignoux; J P Benhamou
Journal:  Gastroenterology       Date:  1978-03       Impact factor: 22.682

8.  Impaired drug metabolism in experimental cirrhosis in the rat.

Authors:  J P Villeneuve; A J Wood; D G Shand; L Rogers; R A Branch
Journal:  Biochem Pharmacol       Date:  1978       Impact factor: 5.858

9.  Uptake of bile acids by perfused rat liver.

Authors:  J Reichen; G Paumgartner
Journal:  Am J Physiol       Date:  1976-09

10.  Increased clearance of antipyrine and d-propranolol after phenobarbital treatment in the monkey. Relative contributions of enzyme induction and increased hepatic blood flow.

Authors:  R A Branch; D G Shand; G R Wilkinson; A S Nies
Journal:  J Clin Invest       Date:  1974-04       Impact factor: 14.808

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  22 in total

Review 1.  Hepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension.

Authors:  H Reynaert; M G Thompson; T Thomas; A Geerts
Journal:  Gut       Date:  2002-04       Impact factor: 23.059

Review 2.  Clinical pharmacokinetics in patients with liver disease.

Authors:  A J McLean; D J Morgan
Journal:  Clin Pharmacokinet       Date:  1991-07       Impact factor: 6.447

Review 3.  Assessment of liver metabolic function. Clinical implications.

Authors:  J Brockmöller; I Roots
Journal:  Clin Pharmacokinet       Date:  1994-09       Impact factor: 6.447

4.  The role of calcium channels and serotonin (5-HT2) receptors for tumour cell lodgement in the liver.

Authors:  G Skolnik; U Bagge; G Blomqvist; L Djärv; H Ahlman
Journal:  Clin Exp Metastasis       Date:  1989 Mar-Apr       Impact factor: 5.150

5.  Effects of calcium antagonists on hepatic and systemic hemodynamics in awake portal hypertensive rats.

Authors:  M Nagasawa; T Kawasaki; T Yoshimi
Journal:  J Gastroenterol       Date:  1996-06       Impact factor: 7.527

6.  Effect of verapamil on nitric oxide synthase in a portal vein-ligated rat model: role of prostaglandin.

Authors:  Chii-Shyan Lay; C-M-Y May; Fa-Yauh Lee; Yang-Te Tsai; Shou-Dong Lee; Shu Chien; Shlomoh Sinchon
Journal:  World J Gastroenterol       Date:  2006-04-21       Impact factor: 5.742

7.  Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

Authors:  J Reichen; B Egger; N Ohara; T B Zeltner; T Zysset; A Zimmermann
Journal:  J Clin Invest       Date:  1988-12       Impact factor: 14.808

8.  In vivo gene transfer of endothelial nitric oxide synthase decreases portal pressure in anaesthetised carbon tetrachloride cirrhotic rats.

Authors:  M Van de Casteele; A Omasta; S Janssens; T Roskams; V Desmet; F Nevens; J Fevery
Journal:  Gut       Date:  2002-09       Impact factor: 23.059

9.  Solvent isotope effect on bile formation in the rat.

Authors:  C Elsing; A Hirlinger; E L Renner; B H Lauterburg; P J Meier; J Reichen
Journal:  Biochem J       Date:  1995-04-01       Impact factor: 3.857

10.  The calcium-channel blocker, verapamil, does not improve portal pressure in patients with alcoholic cirrhosis.

Authors:  C Merkel; A Gatta; M Bolognesi; R Padrini; G F Finucci; P Angeli; A Ruol
Journal:  Br J Clin Pharmacol       Date:  1988-09       Impact factor: 4.335

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