A GENERAL-METHOD FOR THE DETERMINATION OF THE KINETIC STABILITY OF MACROCYCLIC ALKALI-METAL COMPLEXES WITH RATES OF DECOMPLEXATION BELOW 10(-3) S(-1)

A general method has been developed for the determination of kinetic stabilities of macrocyclic alkali-metal complexes with rates of decomplexation (k(d)) below 10(-3) s-1, by use of radioactive isotopes. This method offers the possibility to study the influence of the solvent polarity and of the salt concentration in solution on the rate of decomplexation of macrocyclic metal complexes. Further advantages are the small amounts of ligand required for these determinations and the simplicity of the method. Furthermore, it is possible by this method to study the 'degenerate' exchange of sodium for sodium and of rubidium for rubidium. By this method the kinetic stabilities of the sodium and rubidium complexes of calixspherands 1-4 were determined. Calixspherand 3 forms kinetically very stable complexes with sodium and rubidium cations in acetone and Me2SO in the presence of high concentrations of sodium cations in solution; half-life times of exchange are 855 (Na+) and 528 (Rb+) h in acetone and 352 (Na+) and 845 (Rb+) h in Me2SO, respectively. The results of this method were verified by an independent H-1 NMR spectroscopic method

Inotropic effects of propofol, thiopental, midazolam, etomidate, and ketamine on isolate human atrial muscle

Background: Cardiovascular instability after intravenous induction of anesthesia may be explained partly by direct negative inotropic effects. The direct inotropic influence of etomidate, ketamine, midazolam, propofol, and thiopental on the contractility of isolated human atrial tissue was determined. Effective concentrations were compared with those reported clinically. Methods: Atrial tissue was obtained from 16 patients undergoing coronary bypass surgery. Each fragment was divided into three strips, and one anesthetic was tested per strip in increasing concentrations (10(-6) to 10(-2) M). Strips were stimulated at 0.5 Hz, and maximum isometric force was measured. Induction agents were studied in two groups, group 1 (n = 7) containing thiopental midazolam, and propofol, and group 2 (n = 9) consisting of etomidate, ketamine, and propofol. Results: The tested anesthetics caused a concentration-dependent depression of contractility resulting in complete cessation of contractions at the highest concentrations. The IC(50)s (mean +/- SEMI mu M) for inhibition of the contractility were: thiopental 43 +/- 7.6, propofol 235 +/- 48 (group 1), and 246 +/- 42 (group 2), midazolam 145 +/- 54, etomidate 133 +/- 13, and ketamine 303 +/- 54. Conclusions: This is the first study demonstrating a concentration-dependent negative inotropic effect of intravenous anesthetics in isolated human atrial muscle. No inhibition of myocardial contractility was found in the clinical concentration ranges of propofol, midazolam, and etomidate. In contrast, thiopental showed strong and ketamine showed slight negative inotropic properties. Thus, negative inotropic effects may explain in part the cardiovascular depression on induction of anesthesia with thiopental but not with propofol midazolam, and etomidate. Improvement of hemodynamics after induction of anesthesia with ketamine cannot be explained by intrinsic cardiac stimulation