Direct cardiac effects of coronary site-directed thiopental and its enantiomers: a comparison to propofol in conscious sheep.
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.
Mather
Laurence E
LE
Centre for Anaesthesia and Pain Management Research, University of Sydney, Royal North Shore Hospital, St. Leonards, Australia. lmather@med.usyd.edu.au
Duke
Colin C
CC
Ladd
Leigh A
LA
Copeland
Susan E
SE
Gallagher
Gabrielle
G
Chang
Dennis H T
DH
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007269:Injections, Intra-Arterial; D015742:Propofol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D012756:Sheep; D013237:Stereoisomerism; D013874:Thiopental / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D006993:Hypnotics and Sedatives; D013874:Thiopental; D015742:Propofol