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Purpose: To study the effects of iothalamate sodium and two dosages of iopromide in acute cerebral ischemia on infarction volume, neurologic performance, and mortality in a rat model of middle cerebral artery occlusion., Materials and Methods: Sixty-four rats underwent endovascular occlusion of the middle cerebral artery. Four hours later, 16 animals received iothalamate sodium (588 mg iodine per kilogram); 16, iopromide as a single bolus (518 mg iodine per kilogram); and 16, iopromide as a double bolus (1,036 mg iodine per kilogram). Sixteen animals received equivolumetric saline (control group). Neurologic score and body weight were recorded every 8 hours. Twenty-four hours after occlusion, all animals were killed; brains were stained to assess the infarction size., Results: Single and double doses of iopromide did not affect infarction volume or neurologic performance. Iothalamate caused an increase in infarction volume and worsening of the neurologic score (p < .05). Mortality rate was 25% in the iothalamate group, 12% in the control group, and 6% in the iopromide groups., Conclusion: Bolus injection of the nonionic iopromide does not statistically significantly affect infarction volume or cerebral ischemia symptoms. Nonionic rather than ionic contrast agents should be preferred during acute cerebral ischemia.

Sodium iothalamate was injected intravenously into mice to test the hypothesis that reactions to contrast media are controlled by the central nervous system. Particular emphasis was placed on (a) the effect of the limbic portion of the brain on the hypothalamus and (b) the outflow through the autonomic nervous system. Diazepam and hexamethonium significantly affected the LD50; in addition, in comparison trials with control mice, they markedly decreased the death rate (p < 0.0005). High doses of methylprednisolone sodium succinate, given every 6 hours before the contrast medium, had no effect.

Intravenous injections of ionic contrast media increase extravascular lung water in patients with elevated left atrial pressure, particularly in the presence of myocardial ischemia. The authors compared bolus injections of sodium methylglucamine diatrizoate and iopamidol on extravascular lung water at several levels of left atrial pressure in dogs. Methylglucamine increased lung water by a maximum of approximately 25-30% above baseline levels at low (less than 3 mm Hg), moderate (approximately equal to 15 mm Hg), and elevated left atrial pressures (greater than or equal to 25 mm Hg). At matched pressures, the peak change in lung water in the dogs given iopamidol was +4%, +7%, and +6%, respectively. In dogs with myocardial ischemia, the differences were even more pronounced (+45%, +60%, and +70%, respectively, for ionic media, and +7%, +12%, and +21% for iopamidol). The authors caution against using ionic contrast media in patients with left ventricular dysfunction, particularly associated with ischemia. In such cases, non-ionic media appear safer.

The effect of diatrizoate, ioxitalamate, metrizamide, and ioxaglate on the aortic endothelium of the rat was investigated using transmission electron microscopy and DNA synthesis autoradiography. One milliliter of each contrast medium, containing 300 mg iodine per ml, was injected into the aorta. The types of lesions seen on electron microscopy and the rate of DNA synthesis seen on autoradiography established the degree of endothelial damage that had been produced. Of the four contrast agents tested, ioxaglate produced the least amount of cellular change.

The authors describe an experimental model for the study of nephrotoxicity induced by contrast media, based on a standardized injection combined with occlusion of the renal artery so as to expose the kidney to a high concentration of contrast medium for ten minutes. Iopamidol, ioxaglate, and both isosmolar and hyperosmolar saline were well tolerated, but diatrizoate caused marked radiological and pathological changes. This model may be helpful in studies of the mechanisms underlying contrast medium nephrotoxicity and evaluating differences in toxicity between contrast agents.

Cultured endothelial cells derived from human umbilical cord veins were labeled with Na2 (51Cr)O4 and exposed to pure isoiodinated contrast media or control solutions for 10 minutes to simulate the effects of intravenous injections of contrast media on the human endothelium. Metrizamide, iohexol, iopamidol, meglumine/Ca metrizoate (300 mg I/ml), meglumine/Na diatrizoate, meglumine/Na ioxaglate, and meglumine/Ca metrizoate (200 mg I/ml) were tested. Iso-osmolal mannitol solutions were used to determine the portion of injury that was due to the effects of osmolality. Up to six times more chromium-51 was released from the cultures following exposure to the two hyperosmolal ionic contrast media (meglumine/Na diatrizoate and meglumine/Ca metrizoate) than with exposure to the least toxic agent, iopamidol. The dimer ioxaglate and the three nonionic agents (iohexol, metrizamide, and iopamidol) gave a chromium-51 release rate that was almost equal to or lower than that of 0.9% saline. Follow-up of the washed cultures for 24 hours showed no residual toxic effects.