Uptake and effects of thiopental in isolated heart preparations of the rat in the presence of halothane.

The uptake of thiopental (CAS 76-75-5) (0.13-0.27 mmol.l-1) into tissue of rat hearts (Langendorff's preparation) was studied in the presence of halothane (CAS 151-67-7). Up to a thiopental concentration of 0.19 mmol.l-1 in the perfusion medium its concentration in heart tissue was significantly increased vs. control when halothane (0.8 vol%) simultaneously was present; using 0.13 mmol.l-1 thiopental and 0.8, 1.5 or 2.0 vol% halothane this increase amounted +12%, +29% and +43%, respectively. Frequency of spontaneously beating rat hearts decreased in the presence of increasing thiopental concentrations. 0.8 vol% halothane (without thiopental) did not influence heart rate; in the presence of thiopental it attenuated heart rate reduction. This attenuation was absent in hearts of rats pretreated with reserpine. 1.5 vol% halothane (itself also without influence on heart rate) increased the negative chronotropic action of thiopental. In isolated right and left atria of rat hearts frequency and contractility decreased concentration-dependently in the presence of thiopental; simultaneously present halothane additionally increased this negative chronotropic and negative inotropic effect of thiopental.

Interactions between thiopental and volatile anesthetics (halothane and isoflurane) in isolated heart preparations of the rat.

Thiopental uptake into heart muscle tissue was studied in spontaneously beating rat hearts (Langendorff preparation, 0.13-0.27 mmol/l thiopental in the perfusion fluid). Up to 0.19 mmol/l the concentration of thiopental in heart muscle tissue was increased vs. control when halothane (0.8 vol%) was present. Using a constant thiopental concentration (0.13 mmol/l) and 0.8, 1.5 or 2.0 vol% halothane +12%, +29% or +43% more thiopental was taken up into heart muscle tissue compared to the control. This increased uptake was not seen in the presence of 1.2 and 2.0 vol% isoflurane. Frequency of right rat atria was decreased by increasing thiopental concentrations (0.02-0.23 mmol/l in the incubation medium). Halothane (0.8 and 1.5 vol%) and isoflurane (1.0 and 2.0 vol%) alone had no influence on frequency of right atria. Both volatile anesthetics additionally increased the negative chronotropic action of thiopental when the corresponding higher concentration was applied. Contractile force of left rat atria was decreased concentration-dependently by thiopental (0.02-0.23 mmol/l). Halothane and isoflurane alone decreased contractility. Dependent on the concentration used, both volatile anesthetics further increased the negative inotropic action of thiopental, yet preferentially at higher barbiturate concentrations.

Increase of thiopental concentration in rat tissues due to anesthesia with isoflurane.

Thiopental distribution was studied in rats (30 mg/kg i.v.) anesthetized simultaneously with 1.25 "rat"-MAC isoflurane. The thiopental concentration in serum and several tissues was determined UV-photometrically at 305 nm after extraction and TLC. In the serum of rats anesthetized with isoflurane the thiopental concentration was significantly increased to +39----+74% in comparison to controls during 30 min following the barbiturate injection. Also in liver, brain, heart, kidney, lung and spleen of rats anesthetized with isoflurane the thiopental concentration was significantly increased at 3 and 10 min; at 30 min the difference vs. control had vanished in brain, heart, lung and spleen. Obviously, thiopental was transiently "trapped" during the early distribution phase to a considerable amount in these vessel-rich tissues when anesthesia with isoflurane was simultaneously performed; this pharmacokinetic interaction might be explained at least to some extent hemodynamically; in many tissues regional blood flow is reduced during anesthesia with isoflurane; thereby the "washout" of thiopental from the tissues and the redistribution are delayed.

Increased binding of thiopental in tissue homogenates of the rat in the presence of a volatile anesthetic.

Thiopental (CAS 76-75-5) binding (0.4 mmol.l-1) in tissue homogenate of rats (liver, brain, heart, kidney, lung, spleen and skeletal muscle) was studied by equilibrium dialysis. Percentage of thiopental bound was relatively low in homogenate of brain, lung, spleen and skeletal muscle (14-19%); it was much higher in that of liver, heart and kidney (24-27%). Simultaneously present halothane (11.8 mmol.l-1) increased the percentage of thiopental bound in the homogenate of all tissues investigated at least to a factor of 1.4 (spleen) and maximally of 2.4 (brain). The same phenomenon of an increased thiopental binding in tissue homogenate was found in the presence of 10.3 mmol.l-1 enflurane (except skeletal muscle) and 10.2 mmol.l-1 isoflurane (except kidney, spleen and skeletal muscle), yet to a significantly lower extent in the presence of these halogenated ethers as compared with halothane.

Increase of thiopental concentration in tissues of the rat due to an anesthesia with halothane.

In rats anesthetized with halothane (CAS 151-67-7) (1.5 vol%) and rats without any further treatment (control) the early distribution phase of thiopental (CAS 76-75-5) (i.v. 30 mg/kg) was studied. In serum and 8 tissues thiopental concentration (T) was determined using ultraviolet detection at 305 nm after extraction and TLC. In rats anesthetized with halothane, T in serum was significantly higher during the 30 min following the thiopental injection (at least +27% and maximally +51%) as compared to the control (same dose), and several pharmacokinetic parameters (e.g. central volume of distribution) were found to be changed thereby; furthermore, at 3, 10 and 30 min T was significantly increased in liver, brain, heart, lung and spleen; in kidney and skeletal muscle a rise of T was also seen, however, it occurred later (after 10 and 30 min). T in fat tissue increased time-dependently; a T-difference in adipose tissue between both groups was not observed. Thiopental was "trapped" during the early distribution phase to a considerable extent in the vessel-rich tissues of rats simultaneously anesthetized with halothane; this pharmacokinetic interaction might be explained hemodynamically: in many tissues regional blood flow is reduced by halothane; thereby a delayed "washout" of thiopental from the vessel-rich tissues could take place and redistribution would be delayed; additional factors as e.g. an increased binding of thiopental at tissue proteins could also play a role. An unusually high T was found at least temporarily in myocardial tissue due to this interaction between the two anesthetics.