Document Detail


Right heart failure impairs hepatic oxygenation and theophylline clearance in rats.
MedLine Citation:
PMID:  7791105     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effect of right heart failure on theophylline clearance was investigated in rats in which right ventricular pressure overload was produced by pulmonary artery constriction (PAC). Fifteen wk after the surgery, compared to sham-operated controls (n = 9), PAC rats (n = 9) showed markedly elevated mean central venous pressure (11 +/- 3 vs 1.44 +/- 0.88 mm Hg, P = .0001), and increased right ventricular weight (0.229 +/- 0.047 vs 0.124 +/- 0.013 g/100 g body weight, P = .0001). Centrilobular hepatic congestion was present in all PAC rats and total hepatic oxygen delivery was reduced significantly compared to controls (146 +/- 58 mumols/min vs. 206 +/- 28 mumol/min; P = .025). In the PAC group, theophylline clearance was reduced (0.82 +/- 0.12 ml/min vs. 0.96 +/- 0.13 ml/min in controls; P = .014), and there was a nonlinear correlation between theophylline clearance and total hepatic oxygen delivery (r = .82). These results suggest that in animals with PAC, metabolism of theophylline was impaired as a result of a reduction in total hepatic oxygen delivery. Therefore, in addition to the known effect of reduced hepatic blood flow on the hepatic clearance of "flow limited" drugs, reduction of hepatic oxygen delivery may be another important mechanism that can lead to reduction in hepatic clearance of capacity-limited drugs in congestive heart failure.
Authors:
C Y Ng; P W Angus; H Ghabrial; S T Chou; L Arnolda; D J Morgan; R A Smallwood
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  273     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1995 Jun 
Date Detail:
Created Date:  1995-07-21     Completed Date:  1995-07-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1332-6     Citation Subset:  IM    
Affiliation:
University of Melbourne, Department of Medicine, Heidelberg Repatriation Hospital, Victoria, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiac Output, Low / metabolism*
Liver / metabolism*
Male
Oxidation-Reduction
Oxygen / metabolism*
Pulmonary Artery / physiopathology
Rats
Rats, Sprague-Dawley
Theophylline / pharmacokinetics*
Chemical
Reg. No./Substance:
58-55-9/Theophylline; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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