Document Detail


Direct cardiac effects of coronary site-directed thiopental and its enantiomers: a comparison to propofol in conscious sheep.
MedLine Citation:
PMID:  15277918     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Previous evidence from laboratory animal studies indicates that R-thiopental has a greater margin of safety than either the more potent S-thiopental or the clinically used rac-thiopental. Although thiopental can cause cardiovascular depression from direct myocardial effects as well as indirect central nervous system and peripheral effects, no studies have yet determined whether its myocardial effects are enantioselective. A lesser direct effect would provide further evidence supporting R-thiopental as a preferred single enantiomer replacement for rac-thiopental. METHODS: The direct myocardial effects of the thiopental enantiomers were compared to those of rac-thiopental and propofol, using a crossover design with small incremental doses infused over 3 min, on separate days, into the left coronary arteries of conscious sheep. Hemodynamic and electrocardiographic measurements were acquired, and serial blood samples were collected during the studies for drug analyses. RESULTS: All three forms of thiopental and propofol produced significant hemodynamic effects consisting of dose-related and rapid-onset decreases in left ventricular dP/dtmax and stroke volume, and increases in left coronary blood flow and heart rate. Cardiac output, mean arterial blood pressure, and central venous pressure remained unaltered. The effects did not differ significantly among rac-thiopental, enantiopure R- or S-thiopental, or propofol. Arterial blood drug concentrations were consistently less than those associated with systemic effects. CONCLUSIONS: Although previous evidence indicates that R-thiopental could make a suitable single-enantiomer replacement for rac-thiopental, the current study did not find a significant difference in direct cardiac effects among the thiopental enantiomers, racemate, or propofol.
Authors:
Laurence E Mather; Colin C Duke; Leigh A Ladd; Susan E Copeland; Gabrielle Gallagher; Dennis H T Chang
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Anesthesiology     Volume:  101     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-07-27     Completed Date:  2004-08-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  354-64     Citation Subset:  AIM; IM    
Affiliation:
Centre for Anaesthesia and Pain Management Research, University of Sydney, Royal North Shore Hospital, St. Leonards, Australia. lmather@med.usyd.edu.au
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MeSH Terms
Descriptor/Qualifier:
Animals
Coronary Vessels / drug effects*
Dose-Response Relationship, Drug
Electrocardiography / drug effects
Female
Heart / drug effects*
Hemodynamics / drug effects
Hypnotics and Sedatives / administration & dosage,  pharmacokinetics,  pharmacology*
Injections, Intra-Arterial
Propofol / administration & dosage,  pharmacokinetics,  pharmacology*
Sheep
Stereoisomerism
Thiopental / administration & dosage,  pharmacokinetics,  pharmacology*
Chemical
Reg. No./Substance:
0/Hypnotics and Sedatives; 2078-54-8/Propofol; 76-75-5/Thiopental

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


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