Myocardial uptake of thiopental enantiomers by the isolated perfused rat heart.
Myocardial uptake of thiopental enantiomers by an isolated perfused rat heart preparation was examined after perfusion with protein-free perfusate. Outflow perfusate samples were collected at frequent intervals for 20 min during single-pass perfusion with 10 micrograms/ml racemic thiopental (washin phase) and for another 45 min during perfusion with drug-free perfusate (washout phase). (+)- and (-)-thiopental concentrations were assayed by chiral high-performance liquid chromatography. Heart rate, perfusion pressure, and electro-cardiogram were also monitored. During the washin phase, there was no significant difference between the mean values of the equilibration rate constants of (+)- and (-)-thiopental enantiomers (0.44 +/- 0.07 min-1 and 0.43 +/- 0.09 min-1, respectively, P > 0.05). Mean volumes of distribution of (+)- and (-)-thiopental enantiomers were similar (6.34 +/- 1.20 and 6.45 +/- 1.29 ml/g for the washin phase and 7.22 +/- 0.71 and 7.47 +/- 0.81 ml/g for the washout phase, respectively, P > 0.05). This indicates that tissue accumulation of thiopental enantiomers in the isolated perfused rat heart was not stereoselective. Uptake of thiopental by the heart was perfusion flow rate-limited and independent of capillary permeability. These findings suggest that myocardial tissue concentration of racemic thiopental should be an accurate predictor of myocardial drug effect.
Nguyen
K T
KT
Victorian College of Pharmacy, Monash University, Melbourne, Australia.
Morgan
D J
DJ
D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D001693:Biological Transport, Active; D002851:Chromatography, High Pressure Liquid; D003864:Depression, Chemical; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013874:Thiopental / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics*
D018686:Anesthetics, Intravenous; D013874:Thiopental