| Increased sensitivity of propranolol clearance to reduced oxygen delivery in the isolated perfused cirrhotic rat liver. | |
| | |
MedLine Citation:
|
PMID: 8831600 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND & AIMS: Capillarization of the sinusoids in cirrhosis is proposed to reduce oxygen availability to the hepatocyte, resulting in the patterns of altered drug metabolism observed in cirrhosis. If this were true, drug metabolism in cirrhotic livers would be expected to be more sensitive to reduced oxygen delivery than in noncirrhotic livers. The aim of this study was to compare the sensitivity of propranolol clearance with reduced oxygen delivery in isolated perfused livers from healthy and cirrhotic rats. METHODS: Propranolol clearance was measured at steady state in 5 normal and 5 cirrhotic weight-matched perfused rat livers under single-pass conditions with normal oxygen delivery (mean, 71.5 mumol/min) and with graded reductions in oxygen delivery (range, 58.1-18.8 mumol/min). RESULTS: In noncirrhotic livers, propranolol clearance was independent of oxygen supply for the oxygen delivery range of 73-45 mumol/min but decreased with further reductions in oxygen supply. In cirrhotic livers, propranolol clearance decreased linearly (r2 = 0.92; P < 0.005) for the entire oxygen delivery range (73.4-18.8 mumol/min). CONCLUSIONS: The increased sensitivity of propranolol clearance in perfused cirrhotic livers to reductions in oxygen delivery is consistent with impaired oxygen delivery to hepatocytes in cirrhosis. These novel findings potentially hold implications for clinical management of patients with cirrhosis. |
| | |
Authors:
|
P L Hickey; A J McLean; P W Angus; E F Choo; D J Morgan |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Gastroenterology Volume: 111 ISSN: 0016-5085 ISO Abbreviation: Gastroenterology Publication Date: 1996 Oct |
Date Detail:
|
Created Date: 1996-11-06 Completed Date: 1996-11-06 Revised Date: 2003-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 1039-48 Citation Subset: AIM; IM |
Affiliation:
|
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, Melbourne, Victoria, Australia. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adrenergic beta-Antagonists
/
pharmacokinetics* Animals Cytochrome P-450 Enzyme System / analysis Liver / metabolism* Liver Cirrhosis, Experimental / metabolism* Male Metabolic Clearance Rate Oxygen / metabolism* Oxygen Consumption Perfusion Propranolol / pharmacokinetics* Rats Rats, Wistar Sensitivity and Specificity |
| Chemical | |
Reg. No./Substance:
|
0/Adrenergic beta-Antagonists; 525-66-6/Propranolol; 7782-44-7/Oxygen; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Effects of ischemia on the human pancreas.
Next Document: Evaluation of hyaluronic acid binding ability of hepatic sinusoidal endothelial cells in rats with l...