| Effect of endotoxin shock on the clearance of lidocaine and indocyanine green in the perfused rat liver. | |
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MedLine Citation:
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PMID: 10588516 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Endotoxin administration and cecal ligation and puncture produce significant hepatocellular dysfunction when studied in vivo. Specific factors that are present in vivo after endotoxin administration and cecal ligation and puncture, such as alterations in liver blood flow, circulating mediators, and hypoxia, can alter hepatic function. In this study, we used an isolated perfused liver to evaluate the effects of in vivo administration of endotoxin on hepatic function using indocyanine green (ICG) as a global marker of function and lidocaine and its metabolite, MEGX, as specific markers of the CYP450 enzyme system. Endotoxin (Escherichia coli; 45 mg/kg i.p.) was administered to rats followed by a 6-h monitoring before preparation of the isolated in situ perfused liver. Livers from control and endotoxin groups received either ICG (control, n = 6; endotoxin, n = 5) or lidocaine (control, n = 8; endotoxin, n = 8). A separate group of rats (n = 6) received cimetidine (an inhibitor of the CYP450 enzyme system) at a dose of 80 mg/kg daily for 3 days. Livers were perfused via the portal vein by using a single-pass system with a balanced salt solution 6 h after receiving either endotoxin or saline or 24 h after receiving the last dose of cimetidine. After a 40-min stabilization period, ICG or lidocaine was infused via the portal vein until steady-state concentrations were reached in the venous outflow. The total hepatic clearance and intrinsic hepatic clearance for ICG and lidocaine were unchanged in the livers obtained from endotoxin-treated rats. This model could adequately detect CYP450 inhibition because cimetidine-treated rats had significantly lower initial MEGX concentrations (0.63 +/- 0.03 mg/L) compared with control (0.77 +/- 0.03 mg/L) and endotoxin-treated (0.74 +/- 0.04 mg/L) rats. Septic livers had significantly higher initial hepatic oxygen consumption (HVO2) than did control livers (45 +/- 3 microL/min/g vs 82 +/- 9 microL/min/g). The HVO2 remained higher in the septic livers and significantly increased throughout the study, which demonstrated that the livers remained viable and functional. These data indicate that there is no detectable hepatocellular dysfunction after endotoxin shock using ICG, lidocaine, and MEGX in the isolated perfused liver; therefore the dysfunction reported from in vivo studies may be reversible when the liver is removed from the shocked environment. |
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Authors:
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D S McKindley; C Chichester; R Raymond |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 12 ISSN: 1073-2322 ISO Abbreviation: Shock Publication Date: 1999 Dec |
Date Detail:
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Created Date: 2000-01-11 Completed Date: 2000-01-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 468-72 Citation Subset: IM |
Affiliation:
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University of Rhode Island, College of Pharmacy, Kingston 02881, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anesthetics, Local
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pharmacokinetics* Animals Cimetidine / pharmacology Coloring Agents / pharmacokinetics* Cytochrome P-450 Enzyme System / antagonists & inhibitors, metabolism Endotoxins / toxicity Enzyme Inhibitors / pharmacology Indocyanine Green / pharmacokinetics* Isoenzymes / antagonists & inhibitors, metabolism Lidocaine / analogs & derivatives, analysis, pharmacokinetics* Liver / metabolism* Male Metabolic Clearance Rate Oxygen Consumption Perfusion Rats Rats, Sprague-Dawley Shock, Septic / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Local; 0/Coloring Agents; 0/Endotoxins; 0/Enzyme Inhibitors; 0/Isoenzymes; 137-58-6/Lidocaine; 3599-32-4/Indocyanine Green; 51481-61-9/Cimetidine; 7728-40-7/monoethylglycinexylidide; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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