metrizamide and Hemolysis

The nonionic radiographic contrast material (RCM) metrizamide causes consumption of total complement activity in normal human serum (NHS) in vitro in the absence and to a lesser extent also in the presence of EDTA. The depression of titers of total complement is related to an inactivating effect of metrizamide on component C2. Furthermore, metrizamide induces activation of the alternative pathway as evidenced by the appearance of C3 and factor B cleavage products in NHS, dependent on the presence of divalent cations. Alternative pathway activation is probably mediated by an antagonizing effect of metrizamide on the inactivation of C3b. Unlike ionic RCM, the nonionic substance metrizamide does not lead to cleavage of the internal thiolester bond present in native C3 and C4, at concentrations that produce potent consumption of C3 activity in NHS.

Topics: Complement Activation; Complement C3; Complement C4; Complement C4b; Complement Pathway, Alternative; Contrast Media; Edetic Acid; Hemolysis; Humans; Immunoelectrophoresis; Iodipamide; Metrizamide; Time Factors

A nonionic dimer (DL-3-117) containing a novel substituent (D,L amino-threitol) was synthesized and tested as an intrathecal contrast medium. In the complement-mediated assay, the dimer was approximately half as inhibitory of hemolysis as metrizamide or iopamidol. The lethal dose (LD50) in protozoa was 320 mg I/ml for DL-3-117, 96 mg I/ml for metrizamide, and 101 mg I/ml for iopamidol. The intravenous LD50 of DL-3-117 in mice was 26 g/kg, and in rats it was 12.7 g/kg. The effective dose (ED50) of intradiencephalic injection in rats was 219 mg I/kg for DL-3-117, 61.9 mg I/kg for metrizamide, and 154.1 mg I/kg for iopamidol, which are significantly different. A dose of 300 mg I/kg injected into a permanently cannulated lateral ventricle produced neurofunctional deficits with all contrast media except DL-3-117, which scored equal to Ringer's solution. Metrizamide and iopamidol in the same model, adapted for aversion conditioning, induced aversion with 45 mg I/kg, while DL-3-117 did not condition the rats.

Topics: Animals; Central Nervous System; Contrast Media; Diencephalon; Eukaryota; Female; Hemolysis; Injections, Spinal; Iodobenzoates; Iopamidol; Iothalamic Acid; Lethal Dose 50; Male; Metrizamide; Mice; Radiography; Rats; Triiodobenzoic Acids

Topics: Animals; Contrast Media; Erythrocyte Aggregation; Hemolysis; Humans; Iodipamide; Iodobenzoates; Male; Metrizamide; Metrizoic Acid; Rabbits