The cardiotoxicity of four radiopaque contrast media were studied on spontaneously beating isolated rat atria in order to compare the low-osmolar non-ionic medium, metrizamide, with three other contrast media having different cation compositions. The addition of the ionic contrast media to concentrations of 28 and 84 mg I/ml induced atrial arrhythmias in the following order of potency: meglumine iothalamate greater than meglumine--Na--Ca metrizoate greater than meglumine--Na diatrizoate. No arrhythmias were observed after the addition of metrizamide. Metrizamide had only slight effects on the rate and amplitude of the atrial contractions, and hence the work index was almost unaffected. The highest concentration of the three ionic contrast media had very significant cardiodepressive effects. Meglumine iothalamate had the most severe influence on the spontaneous rate of the contractions, while meglumine--Na diatrizoate induced the greatest initial reduction in the amplitude of the contractions and the work index. The present study indicates that the low-osmolar non-ionic medium, metrizamide, is better tolerated by the myocardium than the ionic contrast media.

Animals↗

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Class III antiarrhythmic action linked with positive inotropy: antiarrhythmic, electrophysiological, and hemodynamic effects of the sea-anemone polypeptide ATX II in the dog heart in situ.

Most antiarrhythmic drugs are more or less negatively inotropic. Positively inotropic properties, however, have been demonstrated for some class III antiarrhythmic drugs. To test the hypothesis that class III antiarrhythmic effect and positive inotropy may be linked, we used the sea-anemone polypeptide ATX II, which in isolated heart muscle preparations has been shown to specifically inhibit the inactivation of the sodium channel and thereby increase action potential duration and inotropy. We used 12 pentobarbital-anesthetized dogs. Atrial arrhythmias were induced by high-rate stimulation of the right atrium in 5 dogs. Cardiac electrophysiological effects were studied by His-bundle electrography, programmed electrical stimulation, and monophasic action potential (MAP) recordings in 7 autonomically blocked dogs. ATX II (1.0-5.0 micrograms/kg i.v.) converted the arrhythmias, and in the autonomically blocked dogs markedly increased atrial and ventricular refractoriness and ventricular MAP duration without influencing atrial or ventricular conduction velocities, heart rate, or AV-nodal refractoriness. ATX II induced a marked increase in left ventricular dP/dt max. The study indicates that ATX II has class III antiarrhythmic effect, and that the electrophysiological and positive inotropic effects of ATX II have a common mechanism.

Action Potentials↗