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Cardiac toxicity of angiographic contrast medium has been documented at the cellular level by using the methods of micro-electrode electrophysiology. Canine Purkinje fibers exposed to contrast medium exhibit a “slow response.” The increased automaticity and slowed conduction inherent in this “slow response” may cause the serious arrhythmias and other adverse effects recorded by electrocardiograms during coronary angiography. Hyperosmolarity plays only a minor role in the observed cellular toxicity. The unphysiologic concentrations of sodium, potassium, and calcium in the tested contrast medium were not responsible for the changes observed. Toxicity is probably an inherent chemical property of iodinated diatrizoate or meglumine ions.