MYOCARDIAL UPTAKE OF THIOPENTAL ENANTIOMERS BY THE ISOLATED-PERFUSED RAT-HEART

Myocardial uptake of thiopental enantiomers by an isolated perfused ra t heart preparation was examined after perfusion with protein-free per fusate. Outflow perfusate samples were collected at frequent intervals for 20 min during single-pass perfusion with 10 mu g/ml racemic thiop ental (washin phase) and for another 45 min during perfusion with drug -free perfusate (washout phase). (+)- and (-)-thiopental concentration s were assayed by chiral high-performance liquid chromatography. Heart rate, perfusion pressure, and electrocardiogram were also monitored. During the washin phase, there was no significant difference between t he mean values of the equilibration rate constants of (+)- and (-)-thi opental 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 m l/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 h eart was not stereoselective. Uptake of thiopental by the heart was pe rfusion flow rate-limited and independent of capillary permeability. T hese findings suggest that myocardial tissue concentration of racemic thiopental should be an accurate predictor of myocardial drug effect. (C) 1996 Wiley-Liss, Inc.